SPOTLIGHT ON PARKINSON’S DISEASE: THE ABC’S …7 PARKINSONIAN SYMPTOMS AND DBS Predictors of Good Response Not DBS Responsive Idiopathic PD Atypical or Parkinson Plus Syndromes

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SPOTLIGHT ON PARKINSON’S DISEASE: THE ABC’S OF DBS

PARKINSON’S DISEASE

TUESDAY JUNE 26, 2018

WELCOME AND INTRODUCTIONS

Stephanie PaulVice President Development and MarketingAmerican Parkinson Disease Association

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PRESENTATION

Jill L. Ostrem, MDCarlin & Ellen Wiegner Endowed Professor of Neurology

Division Chief, UCSF Movement Disorder and Neuromodulation CenterWeill Institute of Neurosciences

University of California San Francisco

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Salary & Grant Support: Educational- Medtronic, Allergan, Boston Scientific AbbVie; Clinical Trials- St Jude Medical, Boston Scientific, Google, Cala Health, Medtronic

Honoraria: None

Speaker’s Bureau: None

Equity & Consulting Agreements: AbbVie, Adamas, Neurocrine, Medtronic

FINANCIAL DISCLOSURES

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• What is DBS?• Who is a candidate?• What is new in DBS for PD?

OUTLINE

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WHAT IS DEEP BRAIN STIMULATION?

• Surgical procedure used to treat a variety of neurological symptoms

• Does not damage the brain, instead influences electrical signals in brain circuits

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DBS LEAD ELECTRODE SELECTION AND STIMULATION PARAMETERS

* The negative electrode exerts the therapeutic effect

Unipolar

0123 off

off

(-)

off

(+) positive

Rate(Hertz)number of pulses per second

Pulse Width(µsec)duration of each stimulus

Amplitudeintensity of stimulation

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• The motor system is composed of interconnected loops• Motor cortex to basal ganglia to thalamus to cortex • System initiates and maintains desired movements while filtering out

undesired movements • In PD, loss of dopamine disrupts communication through these loops• DBS thought to break up the pathological signals

HOW DOES DBS WORK?

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Most Candidates:• Moderate/advanced PD disease• Levodopa-responsive• Experiencing motor fluctuations• Experiencing dyskinesia• “Failed” good control with medical

treatments

WHO IS A CANDIDATE FOR DBS?

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Minority:• Overall milder disease, but:

• Severe rest tremor resistant to levodopa

• Painful off-medication state dystonia• Severe dyskinesia with low doses

levodopa• Disability preventing employment

WHO IS A CANDIDATE FOR DBS?

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• Significant psychiatric illness• Psychosis• Depression

• Cognitive Impairment• Significant medical co-morbidities• Unrealistic goals and expectations

WHO ARE NOT GOOD DBS CANDIDATES?

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• Optimization of medications • Detailed motor testing (on and off

medications)• Neuropsychological testing• Psychiatric evaluation (in some cases)• Pre-operative Brain MRI

PARKINSON’S DISEASE CANDIDACY FOR DBS

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PARKINSONIAN SYMPTOMS AND DBS

Predictors of Good Response Not DBS ResponsiveIdiopathic PD Atypical or Parkinson Plus

SyndromesLD responsive, good ON function LD unresponsiveSymptoms not adequately controlled• Dyskinesia or motor fluctuations• Medication refractory tremor• Frequent or severe OFF periods• Off period disability from:

• Bradykinesia• Rigidity• Tremor• Dystonia

Severe disability during best ON time• Balance and gait impairment• Freezing of gait• Dementia• Depression or psychosis• Older Age?

Most non-motor symptoms

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Identify your patient specific PD symptoms you hope DBS will improve:

REALISTIC EXPECTATIONS FROM DBS

• Tremor• Slow movement • Stiffness• Dyskinesia• Falls/balance• Painful dystonia• Depression/Anxiety• Hallucinations

• Poor Speech• Poor Sleep• Freezing• Unexpected Off time• Medication side effects• Poor dexterity• Motor fluctuations

Are these symptoms DBS responsive?How levodopa responsive are these symptoms?Is tremor and/or dyskinesia in the top 3?

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CUSTOMIZED DBS FOR PD

Which device / Which lead? One or both sides?

Which surgical method?

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STN VS. GPI

Both targets - similar in improving motor symptoms and quality of life in PD

STN GPi

More commonly used target Easier for programming

More medication reduction Possibly less cognitive impact long term

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UPDATES IN DBS FOR PARKINSON’S DISEASE

• Updated indication for PD:• FDA approves DBS for earlier stage PD 2016 (>4 years

disease duration

• New DBS Manufacturers• Medtronic: Activa Series• Abbott: Infinity (US FDA approved 2016) • Boston Scientific: Vercise (US FDA approved 12/2017)

• New DBS surgical methods• Interventional MRI• Intra-operative CT

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Typical Progression and Clinical CourseTypical Progression and Clinical Course

Fahn. Ann NY Acad Sci. 2003;991:1-14.

0 3 8 15 20Years

OnsetDiagnosis

Therapy

Preclinical Phase

HoneymoonPeriod

Motor ComplicationPeriod

ResistantSymptoms

Cognitive Decline

-2 to -6

DBSTherapy ?

HOW EARLY SHOULD WE OFFER DBS FOR PD

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“DBS PD EARLY STIM TRIAL”

2 year long German trial; N= 251 PDEarly motor complications (mean disease duration 7.5 yr)Divided patients to DBS plus medication OR medication alonePrimary objective was measurement of quality of lifeDBS group improved quality of life scores by ~8 pointsBest medical therapy worsened by 0.2 pointsDBS superior in motor disability, activities of daily living, Sinemet-

related complications and on time.• DBS improves quality of life 19

Medtronic Activa System

NEW DBS SYSTEMS

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INFINITY™ ABBOTT/ ST JUDE MEDICAL DBS SYSTEM

• FDA approval 2016• Approved in Australia

and Europe• Constant current device• “Upgradeable” DBS

system- Bluetooth wireless

• Communicates with Apple digital devices

• Directional lead

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DIRECTIONAL LEAD

Intraoperative study, Pollo et al. found 43% less current needed for therapeutic benefit in directional lead

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VERCISE™ BOSTON SCIENTIFIC DBS SYSTEM

• FDA Approval 2017• Constant current device• 8 lead electrodes• Small rechargeable

battery• Fractional current delivery• MRI is not safe

Clinician Programmer

Charger

Remote Control

Charging Collar

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NEW SURGICAL METHODS

Traditional DBS Surgical Procedure

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• Developed at UCSF (ClearPoint system)

• Allows patients to be asleep during the procedure

• Surgical procedure is faster with fewer brain penetrations

Interventional MRI for DBS lead placement“Asleep DBS”

NEW SURGICAL METHODS

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Pros• Comparable efficacy• Accuracy Excellent• No MER

• Reduced brain penetrations

• No physiology expertise needed

• Patient asleep

INTERVENTIONAL MRI

Cons• Technique not readily

available• No intraoperative MRI• MRI suites used 24/7

• Reported outcomes limited to a few centers

• MRI visualization• GPI: Usually good• STN: not always great• VIM: not visible

• Bias of traditionalist: anatomically well placed leads can still be ineffective

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MRI SCANS IN DBS PATIENTS-MEDTRONIC SYSTEMS

• Previously only Head MRI’s were approved with SARs <0.1 W/kg (low frequency power limit)- DBS had to be turned “off”

• FDA approved Medtronic DBS systems for only full-body MRI Conditional Use. (Dec 9, 2015), new measurement

• DBS system can be left “on” now if in bipolar mode, can be done with any coil, 1.5T closed bore magnet.

• Fill out eligibility sheet- Medtronic help (1-800-707-0933), give to radiology staff

• Only applies if:• Activa portfolio DBS (Not Soletra, Kinetra, Active SC model

37602, and model 64001/2 pocket adaptors) – 2 prong connector/adaptor – beginning of 2009 – new systems will be all whole body eligible.

• No broken conductor (lead extension or pocket adaptor), standard IPG placement

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FUTURE ADAPTIVE DBS FOR PD

• Determine signals of parkinsonian state

• Signals that correlates with symptoms severity

• Signals that are modulated by medication/DBS

• New Medtronic IPG (Activa PC+S) allows for • Therapeutic stimulation • Recordings of brain activity

• STN/GPi using DBS lead

• An additional electrode (cortical or other)

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CLOSED-LOOP “ADAPTIVE” PARADIGM

Patient at homePAC

Frequency (Hz)

electrodesFreq

uenc

y (H

z)

PSD

coherence

elec

trod

es

Frequency (Hz)

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• Driven by high prevalence of neurological and psychiatric disorders, massive unmet medical needs in treatment options, robust R&D investments and technology developments

• Expanding DBS indications:

EXPANDING DBS INDICATIONS

• Epilepsy• Tourette’s Syndrome• Depression• Addiction • PTSD• Chronic Pain• Obesity

• Anorexia• Alzheimer’s Disease and Dementia• Tinnitus• Traumatic Brain Injury• Minimally Conscious State• Stroke Recovery• Headache

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UCSF MOVEMENT DISORDERS

NeurosurgeryPhilip Starr, MD, PhDPaul S. Larson, MDEdward F. Chang, MDDaniel Lim, MD, PhDKrzysztof Bankiewicz, MD, PhDCoralie De Hemptinne, PhDWhitney Chen, PhDDoris Wang, MD, PhD

NeuropsychologyCaroline Racine Belkoura, PhD

NursingMonica Volz, FNP, MSKaren Merchant, MSNSusan Heath, MS, RNGina Bringas-Cinco, RNAnnie Li Wong, NP

NeurologyJill Ostrem, MDNicholas Galifianakis, MDCaroline Tanner, MD, PhDMarta San Luciano, MDMaya Katz, MDIan Bledsoe, MD,MSJames Maas, MD, PHDChadwick Christine, MDMichael Aminoff, MDRobert Edwards, MDKen Nakamura, MD, PhDAlexandra Nelson, MD, PhDMichael Geschwind, MDAmy Viehoever, MD, PhDNijee Luthra, MD, PhDCameron Dietiker, MD

FellowsJessica Weinstein, MDKyle Mitchell, MDJennifer Choi, MDEthan Brown, MDMitra Afshari, MDMelissa Heiry, MDIdit Tamir, MD, PhD

Research /Support StaffSarah Wang, PhDKristen Dodenhoff, BAFarah KauserJoncarmen MergenthalerJanet AllenShatara BlackmonYasmeen GonzalezJeverly CalaunanKathleen Comyns, MPHSamantha Betheil, BACheryl Meng, MPH Danilo RomeroKanchi Mehta

PsychiatryAndrea Seritan, MD

Social WorkMonica Eisenhardt, LCSW

ChaplinJudith Long

Physical TherapyNancy Byl, PT, PhDHeather Bhide, PT

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QUESTION & ANSWER

Jill L. Ostrem, MDCarlin & Ellen Wiegner Endowed Professor of Neurology

Division Chief, UCSF Movement Disorder and Neuromodulation CenterWeill Institute of Neurosciences

University of California San Francisco

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CLOSING REMARKS

Stephanie PaulVice President Development and MarketingAmerican Parkinson Disease Association

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FOR ADDITIONAL INFORMATION, ANSWERS TO YOUR QUESTIONS, OR FOR ADDITIONAL RESOURCES

Please visit our websiteapdaparkinson.org

Or call us1-800-223-2732

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