Prof Dr J Beck

Chairman Dept of NeurosurgeryMedical Center ndash University of Freiburg Germany

SIH CSF outflow resistance andother objective measurements

laquoAliquorrhoeraquo

bull (orthostatic) headache

International Classification of Headache Disorders 2018

Spontaneous Idiopathic Hypotens ion

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

bull (orthostatic) headache

International Classification of Headache Disorders 2018

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

Spontaneous Idiopathic Hypotens ion

bull (orthostatic) symptoms

International Classification of Headache Disorders 2018

Schievink et al Neurology 2016 Aug 1687(7)673-9

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

modified

Spontaneous Idiopathic Hypotens ion

Kranz Cephalgia 2015

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

laquoAliquorrhoeraquo

bull (orthostatic) headache

International Classification of Headache Disorders 2018

Spontaneous Idiopathic Hypotens ion

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

bull (orthostatic) headache

International Classification of Headache Disorders 2018

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

Spontaneous Idiopathic Hypotens ion

bull (orthostatic) symptoms

International Classification of Headache Disorders 2018

Schievink et al Neurology 2016 Aug 1687(7)673-9

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

modified

Spontaneous Idiopathic Hypotens ion

Kranz Cephalgia 2015

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

bull (orthostatic) headache

International Classification of Headache Disorders 2018

Spontaneous Idiopathic Hypotens ion

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

bull (orthostatic) headache

International Classification of Headache Disorders 2018

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

Spontaneous Idiopathic Hypotens ion

bull (orthostatic) symptoms

International Classification of Headache Disorders 2018

Schievink et al Neurology 2016 Aug 1687(7)673-9

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

modified

Spontaneous Idiopathic Hypotens ion

Kranz Cephalgia 2015

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

bull (orthostatic) headache

International Classification of Headache Disorders 2018

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

Spontaneous Idiopathic Hypotens ion

bull (orthostatic) symptoms

International Classification of Headache Disorders 2018

Schievink et al Neurology 2016 Aug 1687(7)673-9

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

modified

Spontaneous Idiopathic Hypotens ion

Kranz Cephalgia 2015

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

bull (orthostatic) symptoms

International Classification of Headache Disorders 2018

Schievink et al Neurology 2016 Aug 1687(7)673-9

bull Low CSF pressure lt 6 cm H2O

bull Evidence of CSF leaking on imaging

+or

modified

Spontaneous Idiopathic Hypotens ion

Kranz Cephalgia 2015

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

Kranz Cephalgia 2015

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

copy Neurosurgery Inselspital Bern

Spontaneous Intracrania l Hypotens ion

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

Lumbar infusion test

bull A CSF leak should alter normal CSF parameters

bull A CSF leak implies a low resistance to CSF outflow

Rationale

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

Katzmann and Hussey Neurology 1970

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

A computer system for the identification of the cerebrospinal compensatory modelCzosnyka M1 Batorski L Laniewski P Maksymowicz W KoszewskiW Zaworski W

Acta Neurochir (Wien) 1990105(3-4)112-6

Lumbar infusion test

Beck et al J Neurosurg Spine 2017

0

0

44mmHg

44mmHg

10

10

20

20 2

30min

30min

Lumbar infusion test ndash computerized ICM+reg

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Lumbar infusion test ndash ICM+

bull 31 patients

bull 17 females

bull median 55 years

bull 14 had proven spinal CSF leak

57 gt 6 cm H2O

44 mmHg asymp 6 cm H2O

Lumbar pressure at baseline ndash ICM+reg

R-CSFoutLP-baseline-P

57 14

Beck et al J Neurosurg Spine 2017

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

0

0

44mmHg

44mmHg

10

10

20

20 2

30min

30min

Lumbar infusion test ndash computerized ICM+reg

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Lumbar infusion test ndash ICM+

bull 31 patients

bull 17 females

bull median 55 years

bull 14 had proven spinal CSF leak

57 gt 6 cm H2O

44 mmHg asymp 6 cm H2O

Lumbar pressure at baseline ndash ICM+reg

R-CSFoutLP-baseline-P

57 14

Beck et al J Neurosurg Spine 2017

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Lumbar infusion test ndash ICM+

bull 31 patients

bull 17 females

bull median 55 years

bull 14 had proven spinal CSF leak

57 gt 6 cm H2O

44 mmHg asymp 6 cm H2O

Lumbar pressure at baseline ndash ICM+reg

R-CSFoutLP-baseline-P

57 14

Beck et al J Neurosurg Spine 2017

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Lumbar infusion test ndash ICM+

bull 31 patients

bull 17 females

bull median 55 years

bull 14 had proven spinal CSF leak

57 gt 6 cm H2O

44 mmHg asymp 6 cm H2O

Lumbar pressure at baseline ndash ICM+reg

R-CSFoutLP-baseline-P

57 14

Beck et al J Neurosurg Spine 2017

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

57 gt 6 cm H2O

44 mmHg asymp 6 cm H2O

Lumbar pressure at baseline ndash ICM+reg

R-CSFoutLP-baseline-P

57 14

Beck et al J Neurosurg Spine 2017

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

R-CSFoutLP-baseline-P

57 14

Beck et al J Neurosurg Spine 2017

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Lumbar pressure at baseline

No spinal CSF leak 1177mmHg

Proven spinal CSF leak 526mmHg

Plt0001

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Lumbar pressure at plateau

No spinal CSF leak 3206mmHg

Proven spinal CSF leak 1611mmHg

Plt0001

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Pulse amplitude at baseline

Pulse amplitude (mmHg)

bull The pulse amplitude is a pressure response (ΔP) to the transient increase in intracranial blood volume during a cardiac cycle (ΔV)

bull Due to the exponential shape of the pressurendashvolume curve pulse amplitude increases with increasing pressure

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Pulse amplitude at baseline

No spinal CSF leak 038mmHg

Proven spinal CSF leak 018mmHg

Plt0017

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Pulse amplitude at plateau

No spinal CSF leak 280mmHg

Proven spinal CSF leak 103mmHg

Plt0001

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Resistance to CSF outflow computerized

Resistance to CSF outflow (mmHg(mlmin)

bull The resistance to outflow measures the impedance to CSF drainage

bull It is equal to the effective pressure increase(ICP plateau - ICP baseline) divided by the rate of infusion

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Resistance to CSF outflow computerized

No spinal CSF leak 1178mmHgmlmin

Proven spinal CSF leak 197mmHgmlmin

Plt0001

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Resistance to CSF outflow (Rcsf)

AUC 0958

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Elastance

Elastance

The elastance coefficient describes the stiffness of the cerebrospinal system eg the ability to compensate for a cerebrospinal volume increase

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Elastance

No spinal CSF leak 011mmHg

Proven spinal CSF leak 009mmHg

Plt0237

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Pressure volume index

Pressure volume index (ml)

bull The pressure volume index is the volume that has to be added to raise the pressure 10-fold

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Pressure volume index

No spinal CSF leak 2093ml

Proven spinal CSF leak 2643ml

P=0003

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Results

No leak Proven leak ROC

Median IQR Median IQR P-value AUC

RCSF computerized 11middot78 7middot22ndash15middot20 1middot97 1middot53ndash2middot62 lt0middot001 0middot958

Lumbar pressure plateau 32middot06 27middot71ndash41middot15 16middot11 15middot08ndash18middot91 lt0middot001 0middot942

AMP plateau 2middot80 1middot89ndash4middot40 1middot03 0middot81ndash1middot59 lt0middot001 0middot893

Pressure volume index 20middot93 12middot90ndash23middot04 26middot43 24middot18ndash34middot93 0middot003 0middot888

Lumbar pressure baseline 11middot77 9middot04ndash15middot10 5middot26 2middot75ndash8middot37 lt0middot001 0middot866

AMP baseline 0middot38 0middot17ndash0middot88 0middot18 0middot09ndash0middot26 0middot017 0middot752

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Lumbar infusion test ndash ICM+reg

bull Specific pattern of CSF dynamics

bull Investigator independent

bull Rcsf out may be the best CSK leakspecific diagnostic parameter

Beck et al J Neurosurg Spine 2017

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Anatomy of the Optic Nerve Sheath

bull Ludemann W Berens von Rautenfeld D Samii M Brinker T Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system Child Nerv Syst 21 96-103 2005

wwwglaucomaorgbull

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Results ndash Diameter

No statistically significant difference of ONSD

0538cm plusmn 0middot091 vs 0539cm plusmn 0090 p=0957

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

First in supine position -gt secondary in upright position

Diagnostic work-up CSF-leak-protocol

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Patients with newly suspected SIH

n=44

Patients without activecurrent (or history) of orthostatic headaches

n=26

Patients with activecurrent orthostatic headaches

n=18

Diagnostic work-up CSF-leak-protocol

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Results ndash Diameter

Significant difference between supine and upright position in patients with orthostatic headaches

ONSD Supine = 0549cm plusmn 0097 vs Upright = 0484cm plusmn 0middot095 p=0036

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

JNNP 2015

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Before and After Microsurgical Closure of a CSF leak

bull assessment of the ONSD in Patients with spontaneous intracranial hypotension two times

bull 14 Patients with proven fistula in myelography and surgery

bull compared ONSD before and after surgery

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull Significantly different between supine and upright position before surgerybull 51mm vs 47mm p=0002

bull No significant different between supine and upright position after surgerybull 53mm vs 53mm p=0940

Before and After Microsurgical Closure of a CSF leak

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Δ = -05mm vs 001mmp=0004

Transorbital ultrasound ndash before and after closure of the CSF leak

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Ultrasound of the optic nerve sheath

copyNeurosurgery Bern

Fichtner et al J Neurol Neurosurg Psychiatry August 2015

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Schievink W Cephalgia Dez 2008

Prof J Gralla

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Predicting spinal CSF leaks in intracranial hypotension a scoring system based on brain MRI findings

Tomas Dobrocky1 Lorenz Grunder1 Philipe S Breiding1 Mattia Branca2 Andreas Limacher 2 Pascal J Mosimann1

Pasquale Mordasini1 Felix Zibold1 Levin Haeni3 Christopher M Jesse3 Christian Fung34 Andreas Raabe3 Christian T Ulrich3 Jan Gralla1 Juumlrgen Beck34 Eike I Piechowiak1

Dobrocky Piechowiak et al submitted

(1) University Institute of Diagnostic and Interventional Neuroradiology University of Bern Inselspital Bern Switzerland(2) CTU Bern and Institute of Social and Preventive Medicine (ISPM) University of Bern Switzerland(3) Department of Neurosurgery University of Bern Inselspital Bern Switzerland(4) Department of Neurosurgery Medical Center mdash University of Freiburg Germany

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Orthostatic headache

Dynamic Myelo-CT(repeated)

Diagnostic work-up Bern-Freiburg CSF-leak-protocol

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Myelography

Prooven CSF leakn=73

Study populationn=56

No extrathecal contrastn=45

No or inadequate brain MRIn=17

Patients evaluated for SIH n=118

Brain MRI

+ 60 healthy controls

+ 20 prosp validation

Predicting spinal CSF leaks based on brain MRI findings

Dobrocky Piechowiak et al submitted

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull extrathecal contrast after intrathecal application or

bull visualization during microsurgery

The gold standard for a CSF leak

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Qualitative Quantitative

Engorgement of venous sinus Pontomesencephalic angle

Distended inferior intercavernous sinus Suprasellar cistern

Pachymeningeal enhancement (smooth and diffuse) Prepontine cistern

Midbrain descent (subjective) Midbrain descent (iter to incisural line)

Superficial siderosis Venous-hinge angle

Subdural fluid collection Mamillopontine distance

Superior surface of pituitary (concave flat convex) Pituitary height

Tonsillar herniation (relating to McRae line)

Area cavum veli interpositi

2

2

2

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Dobrocky et al submitted

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull 4 mm

bull 5 mm

bull 65 mm

Suprasellar cistern

Prepontine cistern

Mamillo-pontine distance

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Coefficient

(95-CI)

OR

(95-CI)

p-value Score

Engorgement venous sinus 2middot95 (1middot18 to 4middot72) 19middot12 (3middot26 to 112middot30) 0middot001 2

Pachymeningeal enhancement 4middot04 (2middot50 to 5middot59) 57middot01 (12middot18 to 266middot78) lt0middot001 2

Subdural fluid collection 1middot54 (-0middot10 to 3middot17) 4middot65 (0middot90 to 23middot92) 0middot066 1

Suprasellar cistern (le4 mm) 3middot48 (2middot36 to 4middot60) 32middot32 (10middot55 to 99middot02) lt0middot001 2

Prepontine cistern (le5 mm) 1middot47 (0middot41 to 2middot52) 4middot34 (1middot51 to 12middot47) 0middot007 1

Mamillopontine distance (le 65 mm) 1middot13 (0middot07 to 2middot19) 3middot08 (1middot07 to 8middot90) 0middot037 1

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

patients dural

enhance-

ment

subdural

collec-

tion

venous

engorge-

ment

tonsillar

ectopia

(gt5 mm)

pituitary

enlarge-

ment

inferior

intercaver-

nous sinus

Venous

hinge

Mid

brain

descent

PMA

(in deg)

MPD

(in mm)

Suprasellar

cistern

Normal

imaging

Alcaide12 26 100 50 77 23 50 65 (35-

98)

50

Aslan17 34 68 41 62 27 59 50 8middot4 4middot9 0middot99

Tian18 26 88 38 28 54 17 47middot8

8middot7

5middot4 1middot6

Shankar15 17 71 65 41 71

Watanabe19 18 83 72 72 67 72

Farb11 15 95

Kranz20 99 53

with leak

83 75 61 7

Our study 56 83 54 65 5 47 95 (15) 27 49 11 5middot7 1middot7 3middot1 1middot9 0

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Predicting spinal CSF leaks based on brain MRI findings

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Predicting spinal CSF leaks based on brain MRI findings

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Cutpoint Sensitivity Specificity LR+ LR-

ge1 100middot0 40middot0 1middot7 0middot0

ge2 100middot0 73middot3 3middot8 0middot0

ge3 92middot9 93middot3 13middot9 0middot1

ge4 91middot1 98middot3 54middot7 0middot1

ge5 78middot6 98middot3 47middot1 0middot2

ge6 66middot1 100middot0 0middot3

Derivation cohort

LOW

INTER-MEDIATE

HIGH

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Validation cohort

Cutpoint Sensitivity Specificity LR+ LR-

ge1 1000 33middot3 1middot5 0middot0

ge2 1000 66middot7 3middot0 0middot0

ge3 1000 77middot8 4middot5 0middot0

ge4 1000 88middot9 9middot0 0middot0

ge5 818 88middot9 7middot4 0middot2

ge6 636 88middot9 5middot7 0middot4

LOW

INTER-MEDIATE

HIGH

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

No patient with a proven spinal CSF leak had

a normal brain MR score of 0 or 1

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Timing

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull Diagnostic criteria Low CSF pressure (lt60 mmCSF)(ICHD 3rd Version Cephalgia 2018)

bull Normal CSF pressure is common in up to 23 of patients(Kranz Cephalgia 2015 Beck J Neurosurg Spine 2017)

bull Lumbar infusion testing has proven to be a useful tool(Beck J Neurosurg Spine 2017)

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull Symptoms most severe initially

bull The orthostatic nature of the headachemay become less obvious over time (ICHD 3rd Version Cephalgia 2018 Ducros Lancet 2015 Tyagi Pract Neurol 2016 Lobo BMJ Case Rep 2013 Mokri Headache 2013 Schievink Headache 2011)

bull Opening pressure increases slowly withincreasing symptom duration(Kranz Cephalgia 2015)

Natural history of SIH

Kranz Cephalgia 2015

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Natural history of SIH

Subacute11-52 weeks

Chronicgt52 weeks

Acutele10 weeks

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Update - lumbar infusion test ndash ICM+

bull 137 lumbar infusion tests

bull 533 female

bull Mean age 49 years

bull 69 had proven spinal CSF leak

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Admitted for investigation of possible SIHn = 137

Proven CSF Leakn = 69

No proven CSF Leakn = 68

Chronic symptomsn = 19

Subacute symptomsn = 21

Acute symptomsn = 29

No SIH other Diagnosisn = 56

SIH withoutCSF Leak

n = 12

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Correlation coefficient = 0457 p lt 0001

10 52

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

ns ns

502 721 852

Update - lumbar infusion test ndash ICM+

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

295 785 1415

Update - lumbar infusion test ndash ICM+

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

same patients over time

0

2

4

6

8

10

12

14

Test 1 Test 2

Patient 1

Patient 2

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Type of headache acute vs subacute and chronic

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Type of headache and CSF paramter

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

117 066 041

ns ns

Update - lumbar infusion test ndash ICM+

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

bull Patients with different symptom duration show clearly different profiles of CSF

fluid dynamics

bull Longer symptom duration is associated with an altered CSF fluid dynamics

(normalization) and with atypical symptoms

bull Natural history what is the compensatory mechanism

Lumbar infusion testing over the course of SIH

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Spontaneous Intracrania l Hypotens ion

Thank you

Freiburg im Breisgau

Thank you

Freiburg im Breisgau