10/31/2019

1

DBS for Movement Disorders

Jay L. Shils, PhD, D.ABNM, FASNM, FACNSDirector of Intraoperative Neuromonitoring, Department of Anesthesiology, Rush University Medical

Center, Chicago, ILAssociate Professor, Department of Anesthesiology, Rush University Medical Center, Chicago, IL

COI Slide• Session Title: Practice guidance: Neurophysiologic Techniques for Improving DBS Lead Placement

and Post-Operative Optimization.• Name of Speaker: Jay L. Shils, PhD, D.ABNM, FASNM, FACNS• Disclosures

– Scientific advisory board: Medtronic ($5k-$50k), Globus (<$5k), Depuy Synthes (< $5k).– Scientific research: ANS (SJM) (an Abbott company) (no personal income from study – poster printing

coming from grant money). Neuromonitoring, Neuromodulation, Computational modeling (no commercialor governmental funding).

– Speakers Bureau: None– Stock Holder: None– Stock options: None– Company leadership/board of directors: (1) Engineurix (<$5k) (Neuroscience consulting), (2) Intellihat

(<$5k) (Neuromodulation device for memory), (3) Interstitial technologies (<$5k) (Neuromodulationchemical diffusion device).

– Product Royalties: Elsevier book editor (<$5k) – Subjects: neuromonitoring and neuromodulation.– Travel: None– Society leadership and IONM related boards: ASNM, ISIN, ACNS, ABNM– Patents: (1) Spinal cord implant systems and method, (2) Head worn brain stimulation device and method,

(3) Apparatus for trans-cerebral electrophoresis methods of use thereof, (4) Patient monitoring devices andsystems

– Employed by: Rush University Medical Center

• Some off label use of products will be discussed in this lecture• No commercial product names will be used in this presentation

1

2

10/31/2019

2

Functional Neuromodulation

• Motor Cortical Stimulation

• Spinal Cord Stimulation

• Deep Brain Stimulation

• Peripheral Nerve Stimulation

– Cranial Nerve Stimulation

• Functional Electrical Stimulation

• Micro-Arrays

• Closed versus Open loop stimulation

DBS Applications• Depression

– Subgenual Cingulate (Area 25)– Inferior Thalamic Peduncle– Ventral Capsule / Ventral Striatum– Nucleus Accumbens– STN– Medial Forebrain Bundle– Habenualr nucleus

• Epilepsy– Anterior nucleus of thalamus– Centromedian nucleus of thalamus– STN– Hippocampus– Responsive Neuromodulation

• OCD– Anterior Limb of the IC (HDE)– Dorsal-medial nucleus of the thalamus– Inferior thalamic peduncle– Limbic region of Caudate (Ventral Caudate)– Ventral Caudate/Ventral Striatum– STN– Nucleus Accumbens– Ventral capsule/ventral striatum– Inferior thalamic peduncle

• Tourette’s– CM-PF nucleus of the Thalamus– Anterior Thalamus– Anterior Internal Capsule– Nucleus Accumbens– Gpi

• Multiple Sclerosis Tremor– VIM

• Cluster Headaches– Posterior-medial hypothalamic nucleus

• Movement disorder (PD, ET, Dystonia (HDE))– STN, GPi, VIM– Motor Cortex– Peduculopontine nucleus

• Persistent vegetative state– Anterior Intralaminar Nucleus of the thalamus– GPi

• Eating Disorders– Ventromedial Hypothalamic nucleus

• Anorexia Nervosa– Subcallosal cingulate– Ventral striatum– Nucleus Accumbens

• Pain– Ventral Caudal nucleus of Thalamus– Periaqueductal gray– Ventromedial hypothalamus– Anterior capsule– Spinal Cord

• Respiratory Airway Relaxation in Asthma– Periaqueductal gray

• Addiction– Nucleus Accumbens

• Memory (Alzheimers)– Nucleus Accumbens– Hippocampus– Entorhinal cortex

Not FDA Approved

3

4

10/31/2019

3

IONM Modalities• Electrical stimulation evoked potentials

– Sensory

– Motor

• Task related evoked potentials– Limb movement

– Image processing

– Language processing

• Free running biologic signal recording– Single and multi-unit recordings

– Electroencephalograpy – surface and intracranial

– Electromyography

Keller CJ, et. al., Mapping human brain networks with cortico-cortico evoked potentials. Philosophical Transactions B. 2014;369(1653):1-14

5

6

10/31/2019

4

Why Intraoperative Physiology• Structures are composed of multiple

functional components

• Cannot visually differentiate thesefunctional regions on todays imagining

• Need a functional measurement tool inthe operating room

• *MRI is still not accurate enough todetermine boarders

Optic

*Verhagen R; Schuurman PR; van den Munckhof P; Contarino MF; de Bie RM; Bour LJ. Comparative study of microelectrode recording-based STN location and MRI-based STN location inlow to ultra-high field (7.0 T) T2-weigthed MRI images. Journal of Neural Engineering. 13(6):066009, 2016 Oct 14.

Target Localization: MER Information

• Electrode Depth– Expectations

• Activity– Present– Absent– Robustness

• Activity Type– Single unit– Multi unit– LFP

• Single Unit Activity– Resting discharges– Background activity– Discharge pattern

• Tonic• Phasic / Arrhythmic• Bursting• Rhythmic

• Discharge Frequency Modulation– Modulated with active

movement– Modulated with passive

movement / somatic stimulation– Modulated with abnormal

movement

7

8

10/31/2019

5

Physiologic Testing Modalities

• Positive responses– Improvement of negative

manifestations of each diseaseand pharmacological treatments:

• Tremor

• Bradykinesia (Akinesia)

• Rigidity

• Dyskinesia

• Feeling “Happy”

• Parasthesia in painful area

• Adverse effects– Generation of new symptoms or

worsening of existing symptomsat “usable” stimulation levels

• Parasthesias

• Contractions

• Visual changes

• Visceral effects

• Single Unit Recordings• Use of single unit firing patterns to define structural

and functional boundaries - Mapping

• Electrical Stimulation• Map local response to electrical stimuli• Use external stimuli to evoked either

9

10

10/31/2019

6

General Considerations

• Patient State at Start of Surgery

• Last Medications

• Peripheral Issues– Bone/Muscle/Joint Problems

– Hearing Difficulty

– Vision Difficulty

• Degree of Speech Impairment

• Baseline Blood Pressure

• Respiratory Issues

The STN Target

POSTERIOR

ANTERIOR

INFERIOR / VENTRAL

SUPERIOR / DORSAL

LATERAL

MEDIAL

STN

SNr

CSTZi

11

12

10/31/2019

7

Axial / Coronal / Sagittal

Coronal

Sagittal

Axial

Stereotactic Accuracy: STN

• Size– ~ 10 mm (R-C)

– ~ 10 mm (M-L)

– ~ 6 mm (D-V)

• Location– > 90 mm of electrode

travel to STN fromextracranial ‘startposition’

Neighborhood Zona Incerta

Internal Capsule

Optic Tract

Medial Lemniscus

Ventral Thalamic Tier

Substantia Nigra (SNr)

Coronal – 3.0 Posterior to MCPSchaltenbrand-Wharren Stereotactic Atlas

Sagittal – 12.0 Lateral to MidlineSchaltenbrand-Wharren Stereotactic Atlas

12.0 mm from Midline 3.0 mm Posterior to MCP

13

14

10/31/2019

8

Wrist Kinesthetic Cell

15

16

10/31/2019

9

Does Every STN Cell Fire the Same Way ?

Multiple Single Units From One Patient

17

18

10/31/2019

10

Data Map – Trajectory Angle

1

10

20

1

10

20

1

10

20

19

20

10/31/2019

11

10.512.013.0

ThalamusSTNSNr

STN Stimulation and AE’sParesthesias and otherSensory Phenomena

Diplopia and otherOculomotor Phenomena

Affective Disorders

Motor Contractions

STN

21

22

10/31/2019

12

Intra-Operative Example

Data Map – Trajectory Angle

1

10

20

1

10

20

23

24

10/31/2019

13

Data Map – Trajectory Angle

1

10

20

Data Map – Trajectory Angle

1

10

20

25

26

10/31/2019

14

Where are you?

• Track 1 results

– Large segment of thalamus

– Large quiet zone

– ? STN in the background

– SNr activity deep

• Patient alert and responsive the whole tract

12.0 mm Lateral

12.0

Large Seg. ThalamusLarge Quiet Zone? STNSNr

distance betweenSTN and SNr

No ThalamusLarge Quiet Zone? STNSNr but distancebetween STN and SNr

Is this a potentiallygood trajectory?

Is this a potentiallygood trajectory?

27

28

10/31/2019

15

12.0

Why wont thisTrajectoryWork for the fit ?

The angle is fixed bythe surgeon on thestereotactic frame

12.0 mm Lateral

10.5 mm Lateral

Large Seg. ThalamusLarge Quiet Zone? STNSNr but distancebetween STN and SNr

Large Seg. ThalamusLarge Quiet Zone? STNSNr and STN close

Is this a potentiallygood trajectory? Is this a potentially

good trajectory?

29

30

10/31/2019

16

9.0 mm Lateral

9.0

Large Seg. ThalamusLarge Quiet Zone? STNSNr but distancebetween STN and SNr

Moderate Seg.ThalamusLarge Quiet Zone? STNSNr but distancebetween STN andSNr

Is this a potentiallygood trajectory? Is this a potentially

good trajectory?

What do you do next?

• There are at least 4 reasonable trajectories

• Do you perform a second recording tract?

– Let us say the patient is getting very agitated and thesurgeon is pushing to move forward with no secondrecording trajectory or to give anesthetic

• Can the STN / SNr distance tell us something ?

12.0 10.5 9.0

The medial locations(9.0 and 10.5) thedistance is about thesame but for the 12.0laterality the distance ismuch smaller – giventhere was a largedistance between STNand SNr 9.0 or 10.5seems most appropriate

31

32

10/31/2019

17

GPi Surgeries

• Ablation

– Place a ThermalLesion in thePosterior-Ventral-Lateral Portion of theGpi

• DBS

– Place a StimulatingElectrode in the sameArea

Optic

GPi

GPe

Putamen

Axial / CoronalCoronalAxial

Late

ral

Med

ial

Med

ial

Late

ral

Anterior

Posterior Ventral

Dorsal

33

34

10/31/2019

18

Intraoperative Neurophysiology

• Find GPi

• GPe / GPi Size Relationship

• Sensory Motor Region

– Posterior-Ventral-Lateral

• Activity

• Disease

• Prior Movement Disorder Surgery

• Internal Capsule

• Optic Tract

Optic

GPi

GPe

Putamen

GPi

JLS 2015

35

36

10/31/2019

19

GPi Stimulation AE’s

Depression ???

Poor Motor Control

Muscle Contractions

Vision Effects

GPi

Different Disease Different Patterning

37

38

10/31/2019

20

GPi MER Recording: DYT-1

Dexmedetomidine(Presedex)

Propofol

No Anesthetic

STN on dex(0.7g/kg/hr)-Pt. J; Side 1 STN on prop. (20g/kg/min) – Pt. J; Side 2

Agent # of Patients Total # of Cells Average # of Cells perPatient

No Anesthetic 3 22 7.3

Propofol 3 11 3.7

Dex. 2 14 7.0

GPi on dex (0.7g/kg/hr)-Pt. M; Side 1 GPi on prop. (20g/kg/min)-Pt. G; Side 1

Dexmedetomidine vs. Propofol MER

39

40

10/31/2019

21

ExampleIntra-Operative Management

Striatum – Similar to PD

GPe – Pre and Post Electrode Conditioning - Similar to PD – 52 to 70 Hz firing

Recordings

41

42

10/31/2019

22

Ankle Accel.

Wrist Accel.

Quad

Tricep

Bicep

Where are we?Is there any information here?

Ankle Accel.

Wrist Accel.

Quad

Tricep

Bicep

What do we hear and see?

Maybe a little slower than GPe from two slides prior(but average firing rate is the Same)

Less “Stuttering”

43

44

10/31/2019

23

Where is GPi is this recording ?

What is this activity?

Boarder UnitWe now have some

Spatial Information

45

46

10/31/2019

24

Where is GPi is this recording ?

What does this signify?

Coming out of GPi

Flashes of light

47

48

10/31/2019

25

Brain DictionaryThalamus STN GPi

Literature (what is important about MER)Umemura

• Investigated single tract MER findings• Compared to surgical outcomes• N=440 sides in 221 patients• Looked at:

– STN activity– the amount of STN traversed– Passive joint movements

• If 1st trajectory did not show enough STN theywould move 2mm in the direction indicated byfunctional mapping

Umemura a, Oka Y, Yamada K, et. al. Validity of single tract microelectrode recording in subthalamic nucleus stimulation. Neurol Med Chir (Tokyo).2013;53:821-827.

49

50

10/31/2019

26

LiteratureUmemura

• 2 patients had symptomatic ICH with hemiparesisand recovered within a year with rehabilitation

– Their PD symptoms improved

Umemura A, Oka Y, Yamada K, et. al. Validity of single tract microelectrode recording in subthalamic nucleus stimulation. Neurol Med Chir (Tokyo).2013;53:821-827.

LiteratureUmemura

• The second side wouldstart at the mirror of thefirst sides final trajectorynot at the stereotacticchosen coordinates

• The authors concludethat anterior/posteriormoves should beconsidered first beforetrying medial/lateralmoves

Umemura A, Oka Y, Yamada K, et. al. Validity of single tract microelectrode recording in subthalamic nucleus stimulation. Neurol Med Chir (Tokyo).2013;53:821-827.

51

52

10/31/2019

27

DBS vs BMT

• Compared DBS + Medication to Best MedicalTherapy

• N=156 patients with advanced PD– Baseline and at 6 months comparison

• Looked at– Motor scores

• UPDRS III

– Quality of life scores• PDQ-39

Deuschl G, Schade-Brittinger C, Krack P, et. al. A randomized trial of Deep-Brain stimulation for Parkinson’s disease. NEJM. 2006;355:896-908

DBS vs BMT

• All patients were pre-screened prior to DBS

• Acceptable candidates were randomized toDBS or best medical therapy

Deuschl G, Schade-Brittinger C, Krack P, et. al. A randomized trial of Deep-Brain stimulation for Parkinson’s disease. NEJM. 2006;355:896-908

53

54

10/31/2019

28

DBS vs BMT

Deuschl G, Schade-Brittinger C, Krack P, et. al. A randomized trial of Deep-Brain stimulation for Parkinson’s disease. NEJM. 2006;355:896-908

DBS vs BMT

Deuschl G, Schade-Brittinger C, Krack P, et. al. A randomized trial of Deep-Brain stimulation for Parkinson’s disease. NEJM. 2006;355:896-908

55

56

10/31/2019

29

DBS vs BMT

• Conclusion

• “In this six-month study of patients under 75years of age with severe motor complicationsof Parkinson’s disease, neurostimulation ofthe Subthlamaic nucleus was more effectivethan medical management alone.”

Deuschl G, Schade-Brittinger C, Krack P. A randomized trial of Deep-Brain stimulation for Parkinson’s disease. NEJM. 2006;355:896-908

Conclusion

• Physiologic target

• Changing surgical paradigm

• More complex field shaping leads

• MER versus other neurophysiologictechniques

• Intra-operative physiology is still necessary

57

58

10/31/2019

30

Special Thanks• Kenneth Casey, MD

• Michael Munz, MD

• Ron Alterman, MD

• Jeff Arle, MD, PhD

• Sepher Sani, MD

• Ryan Kochanski, MD

• Howard Hurtig, MD

• Mathew Stern, MD

• Amy Cholcher, MD

• Tanya Simuni, MD

• Michele Tagliati, MD

• John Rogers, MD

• Diana Apetauerova, MD

• Julie Leegwater-Kim, MD, PhD

• Leo Verhagen, MD, PhD

• Gian Pal, MD

Jay_l_shils@rush.edu

59