Neurological Complications of EDS: Instability the craniocervical junction and cervical spine

Fraser C. Henderson Sr

Chief ,Neurosurgery Luminis Health, DCH,MD

Director, The Metropolitan Neurosurgery Group

Staff, University of Maryland Capital Region MC

Disclosures

◼ Scientific Board, Computational BioDynamics, LLC

◼ Inventor: Stress Injury Analysis Computer Simulation Model For Human Central Nervous System. Henderson. U.S. Patent # 6,980,922 doi 12/27/2005

◼ Inventor: Theory, method and Device for Determination of Abnormal Brainstem stress and subsequent neurological deficit. Henderson:

U.S. patent # 8858470 doi 01/29/2007

◼ Inventor : Mathematical Relationship of Strain, Neurological Dysfunction and Abnormal Behavior Resulting from Neurological Dysfunction of the Brainstem: Henderson FC, Newman JW:

U.S. Patent # 8556939 doi 01/08/2008

◼ Inventor : Craniospinal Fusion Method and Apparatus: Henderson US Patent # 8,182,511 doi 5/29/2012

◼ Consultant , Life Spine , Inc

26 y.o. woman, formerly a vocalist

◼ Masters in music at Cambridge◼ MVA 2009, bedrest since then◼ Headache (8/10) and diffuse joint pains◼ Nausea◼ Memory and cognition problems◼ Visual blurring, photosensitivity, hyperacusis◼ Dizziness, episodes of syncope, POTS◼ Weakness, imbalance, incoordination◼ Unstable joints with frequent subluxation◼ unable to walk > 20 feet◼ Urinary urgency , incontinence

Chiari Malformation Type 1, Basilar invagination, Atlantoaxial instability, cervical segmental instability

Ligamentous laxity results in deformation of the nervous system in EDS

Van Depaepe A, Malfait F: , Clin Genet : 82: 1–11, 2012Voermans et al, Annals of Neurol, 2009

In assessing for the potential of basilar invagination and craniospinal instability : 3 radiological metrics

• Clivo-axial angle, CXA

• Grabb,Mapstone,Oakes measurement pB-C2

• Harris’ measurement, BAI

The Consensus Statement, Chiari Syringomyelia Foundation Multi-disciplinary Colloquium Craniocervical Hypermobility Francisco, Oct 19th, 2013

Clinical research common data elements (CDEs):Radiological metrics standardization for craniocervical instability.https://commondataelements.ninds.nih.gov/CM.aspx#66=Data_Standards.Updated 2016.Adopted by the NIH/NINDS CommonDataEquivalents 2018

flexion/ extension CT or MRI recommended where possible

1. Clival-axial angle (CXA)

< 135◦>150 ◦

PATHOLOGICALNORMAL

Ventral brainstem compression – if the Grabb-Oakes measurement >9mm

Harris measurement Abnormal >12mm

Normally, the basion pivots over the mid odontoid, translational movement is < 1 mm

Weisel, Rothman, 1979 Werne, 1957 Fl White and Punjabi 1980 Fielding 1957 Menezes, 1990 Henderson 2017,2018

>1 mm translation between cranium and odontoid is Pathological (White,Panjabi,1990)

Harris measurement BAI = 12mm Harris measurement BAI = 7mm

Chronic Craniocervical instability translation >1 mm is pathological

Indications for cranio-cervical fusion stabilization

• exhausted non-operative treatment

• surgery is a last option

• disabling headache/neck pain >7/10

• Cervical medullary syndrome

• neurological deficits

• pathological radiological metrics

The cervical medullary syndrome

HeadachesDizziness, vertigo, tinnitus ImbalanceGait changesSensori-motor deficits Visual and auditory deficitsDysarthria, dysphagia , chokingAltered breathing , sleep apneaNausea, emesissyncope

Consensus conference , CSF, San Francisco, 2013

Operative Procedure

• SSEPs• Limited suboccipital

decompression, no duroplasty• Screw fixation per Goel• rib harvest T7 for fusion• Cut time 3 hours• EBL average <100ml

Craniocervical fusion stabilization

Iliac crest allograft soaked with bone marrow aspirate, incorporated into aperture of occipital plate

Hospital outcomes

◼ surgical cohort= 50 surgical patients non-surgical comparison cohort =22

◼ mean hospital LOS = 4 days

◼ no intra-operative complications

◼ 6 unplanned reoperations related to poor wound healing, of which 1 underwent revision of fusion

At follow-up, surgical cohort reported taking less pain medication (p-value = 0.001)

Pre-post surgery symptom improvement)

NEUROLOGICAL ▪ Dizziness /

lightheadedness▪ Presyncope ▪ syncope▪ Headache▪ Neck pain▪ Concentration

difficulties ▪ Nausea / vomiting ▪ Incoordination

CONSTITUTIONAL • Fatigue

MUSCULOSKELETAL• Joint pain • Neck pain on bumpy

roads • Muscle pain at rest

Symptoms reaching statistical significance p<0.001

pre-post surgery symptom improvement

NEUROLOGICAL ▪ Vertigo ▪ Dystonias▪ Memory loss▪ Double vision▪ Photosensitivity▪ Facial numbness▪ Leg weakness▪ Arm weakness▪ Speech difficulty▪ phonosensitivity

MUSCULOSKELETAL• Cramps, stiff muscles• Pain in legs while

walking

GASTROINTESTINAL • Abdominal pain• Bloating• Constipation• Heartburn, GERD• Diarrhea

DYSAUTONOMIAstatistical significance ( p < 0.05)lpitations• Chest tight, pain at

rest• Chest pain on

exertion• Short breath at night• Short breath at rest• Fingers change color

(Raynaud-like phenomena)

• Heat intolerance• Elevated

temperature

Karnofsky Performance Score

p-value = 0.044

p-value = 0.033

70 Cares for self; unable to carry on normal activity or to do active work.

60 Requires occasional assistance, but is able to care for most of his personal needs.

50 Requires considerable assistance and frequent medical care.

40 Disabled; requires special care and assistance.

Patients reported high satisfaction with their surgery.

“In looking back, I would still choose to have the cranio-cervical surgery.”

Atlanto-axial instability

Alar ligament incompetence is a cause of AAI

• rotational movement (23-39°) restricted by contralateral alar ligament

• “.. overstretching or rupture of the alar ligaments can result in rotary hypermobility or instability”

- Harold HoffmanDvorak JRI, Panjabi M, Gerber M, Wichmann W. CT Functional diagnostics of the Rotary Instability of Upper Cervical Spine , Spine ,1987

86% of patients RA exhibit anterioratlantoaxial subluxation (AAS) stroke and sudden death due vertebrobasilar insufficiency Anterior AAS is the most common form (80%)

BUT in EDS the subluxation is lateral

AAI dx by open mouth views on DMX or CT

Lateral translation

Alar ligament incompetence demonstrated by stressing the alar ligaments with rotation of the cervical spine

neck rotated to left, angle subtended by C1 upon C2

Therefore , the C1-C2 angle is 45 °

N N

>80% facet subluxation = unstable

UNSTABLE

>80% loss of facet overlap

Atlanto-dental interval normal

Unilateral facet subluxation

facet joint not subluxed

Mechanical deformative stress

Altered vertebro-basilar circulation

Indications for C1C2 fusion stabilization

• Occipital neuralgia• Posterior circulation sx - altered vision - pre-syncope or syncope• intermittent dysesthesias • Nausea• Tinnitus• Impaired memory and

concentration

• Tenderness over C1C2• Hyperreflexia• Diffuse hypoesthesia to

pinprick• Dysdiadochokinesia,

unsteady gait, Romberg• Imaging of subluxation -

- neck rotation - lateral tilt - Impaired vertebral artery flow

Occipital Neuralgia

• Severe suboccipital h/ache

• misdiagnosed as tension headache or migraine

• worse with neck movement, extension , bumpy ride

• neurological exam intact

Fusion with structural allograft infused with bone marrow

Treatment requires careful positioning of screws for stabilization

P =0.003 P < 0.003

Headache and neck pain

Statistically significant improvement in Syncope , presyncope and lightheadedness

P = 0.008

P= 0.018

Karnofsky performance scale

Overall improvement in 65%, no significant improvement in 35%

EDS: premature DDD and osteoarthritis

• Early-onset of cervical spine DDD and osteoarthritic changes

Grahame R. Clinical conundrum. Br J Rheumatol.1989 ;28:320.

Lewkonia RM. Does generalized articular hypermobility predispose to generalized osteoarthritis? Clin Exp Rheumatol.1986 ;4:115–119.

Cervical instability / stretch myelopathy

Physiological tethering through deformity Benzel ,Neurosurg 2007

Henderson et al, Neurosurg 56 :1101-1113, 2005

White and Punjabi, 1990

Cervical Segmental instability C45

NORMAL On standard MRI

Abnormal on dynamic MRI

Symptoms of high cervical instability may mimic some sx of CCI

◼ Headache◼ Nausea◼ Poor memory ,

concentration◼ Change in gait

◼ Neck shoulder pain◼ Interscapular muscle pain

(rhomboid mm)◼ Arm sensory and motor

changes◼ Dyspnea◼ Convergence fatigue

Clinical Instability ≥5 = unstable

2 points each

◼ Sagittal plane displacement > 3.5 mm • sagittal plane angulation > 11 degrees • Spinal cord damage 1 pt each◼ Stenosis Sagittal diameter < 13 mm ◼ Abnormal disc narrowing ◼ Nerve root damage

Headaches due to tethered cord

• 50% tethered cord pts report “ pulling down the back of the head”

• Headache worsens with traction , straight leg raising, neck flexion

• Moderate severe pain

Tethered cord syndrome• Low back pain• Leg weakness, sensory loss , pain• Neurogenic bladder• Sometimes rectal incontinence

• Urodynamic findings• Radiologic findings: fatty filum, low conus

Tethered cord syndrome (may be radiologically occult)

Vascular problems

Potential for vasculopathy

◼ vEDS◼ cEDS 1subtype heterozygous variant of COL1A1, encoding the alpha-1 chain of type I collagen

◼ Classic-like EDS (tenascin X ) ◼ Kyphoscoliotic EDS (kEDS), congenital

hypotonia, rupture or aneurysm of medium-sized arteries.

EDS vascular complications

◼ Dissection of right renal artery

◼ vascular type v EDS (Col 3A1)

◼ Classic –like cl EDS (Tenascin x)heterozygous variant of COL1A1, encoding the alpha-1 chain of type I collagen

◼ Kyphoscoliotic EDS ( kEDS) PLOD 1 or FKBP14 genes

Vertebral artery kinks and carotid dissection

Vertebral artery loops, dissection

Normal VA

Hypercoagulability, sinus thrombosis and decreased venous drainage

Sinus thromboses

◼ left transverse sinus thrombosis

◼ sinus rectus thrombosis◼ SX: Headache,

confusion, personality change, leg weakness, incontinence, coma

◼ Dx: CTA

◼ Treament: Lovenox 1 mg/kg SQ bid

Vascular congestion

• obstruction of venous flow – transverse sinus stenosis - jugular compression• venous congestion • increased bleeding

• Preserve perivertebral venous drainage

◼ Thank you for your attention !!

Acknowledgements

◼ Clair Francomano MD, JHI◼ Myles Koby MD, NIH, Doctors Hospital◼ Peter Rowe MD,JHI◼ Rodney Grahame, Professor of Rheumatology, London Univ◼ Alan Pocinki MD, George Washington University◼ Ed Benzel MD- Prof, Chair Neurosurg ,Cleveland Clinic◼ Robert Gerwin MD Assoc Prof, JHI◼ Alex Vaccaro MD- Prof Neurosurg Ortho, TJU◼ Stephen Mott MD Assoc Prof Peds Neurol, Dartmouth◼ Joel Berry PhD – Prof Chair Mech Eng, Kettering Univ ◼ Mark Alexander MD , Director Neuroradiology Bethesda MRI◼ Jonah Murdoch, MD, GUH,DCH◼ Jessica Adcock BS,MS◼ William Wilson IV, Yale Univ◼ Kelly Tuchman BA, ASN