Deep Brain Stimulation for Essential Tremor

Mya Schiess, MD Professor of Neurology Albert Fenoy, MD Assistant Professor of Neurosurgery

Essential Tremor (ET)

• Tremor is the most common movement disorder

• ET-roughly 5% prevalence in the general population

• Advancing age is a risk factor

• >60 years – prevalence is 9%

• Highest incidence - 6th – 8th decades

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Essential Tremor • Positive family history Benign Familial Tremor

• Male >Female

• Involuntary, rhythmic, oscillatory movement

• Alcohol reduces tremor in 50-90% of cases

– Most often a kinetic tremor (specific action)

– Upper extremities (arms and hands)

– Head – “yes-yes” or “no-no”

– Voice, tongue and chin

– Lower extremities (legs)

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Characteristic Features

• Postural and kinetic tremor with a variable amplitude and a frequency.

• Present during voluntary movement

• Over time may increase in severity and distribution

• Co-occurrence of cerebellar features like ataxia

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Treatment Options >>>>>>> Lifestyle changes

• Avoid or minimize exacerbating factors (e.g. stress, tremor provoking drugs).

• Consider limiting Caffeine-containing beverages

• Alcohol reduces the amplitude of ET in 2/3 of patients

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Pharmacologic Approaches

• 30 to 70 % improvement in tremor control at best

• Drug side effects potential to exceed benefit or worsen with increasing need to escalate dose

• 1st line Beta-blockers such as propranolol (Inderal®)

• 1st line Primidone (Mysoline®)

• Combination primidone/propranolol therapy

• 2nd Line Topirimate; Gabapentin

• Calcium channel blockers

• Carbonic anhydrase inhibitors

• Botulinum toxin type A (BOTOX®)

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When Should DBS therapy be considered ?

Best candidates:

• Moderate to severe tremor: Distal hand tremor and higher frequency .

• Tremor is refractory to medical management

• Limited benefit due to medication side effects.

• Tremor impairs activities of daily living or impacts quality of life

.

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DBS Approved Indications

• DBS Therapy is approved for the treatment of symptoms due to: – Essential Tremor

• FDA approved in 1997

– Parkinson’s disease

• FDA approved in 2002

– Dystonia

• FDA approved (HDE*) in 2003

*Humanitarian Device: Authorized by Federal Law for the use as an aid in the management of

chronic, intractable (drug refractory) primary dystonia, including generalized and segmental

dystonia, hemidystonia, and cervical dystonia, for individuals 7 years of age and older.

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Targets for Tremor Control

• VIM- thalamus : widely used, beneficial in upper extremity tremor.

• Bilateral VIM associated with higher prevalence of dysarthria, dysphagia and balance problems (used to achieve better results in head and voice tremor)

• Dentato-rubral tract (DRT) - available option for axial and cerebellar outflow tremor that are poorly responsive to VIM.

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DBS efficacy for ET

• 70-90% of Essential Tremor patients experience total or significant suppression of disabling tremor *

• Stimulation-induced adverse effects include transient paresthesia, dysarthria, and disequilibrium – Many of the side effects are temporary or

improved with adjustment of electrical parameters

* Data on File. Medtronic, Inc.

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Mya Schiess, MD Professor of Neurology Albert Fenoy, MD Assistant Professor of Neurosurgery

DEEP BRAIN STIMULATION FOR PARKINSONS DISEASE

Parkinson’s Disease The Basics

• What is Parkinson’s disease? 2nd most common neurodegenerative disorder after Alzheimer’s Dementia

• SLOWLY progressive • Chronic disorder • Affects an individual over 40 years of their lifespan • Very treatable, not yet curable • Non-motor symptoms precede the motor symptoms by years

to decades • No known biomarker for disease diagnosis or progression

Clinical symptoms develop after 70-80% of striatal dopamine is depleted

Corresponds to 30-50% cell death of dopaminergic neurons

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• Affecting 0.7% of people ≥ 65 years of age worldwide

• Incidence increases with age

• Men are slightly more affected

• Men : women 3:2

• Average age at diagnosis: 55-60 yrs

• Majority of cases (90%) are sporadic

De Lau & Breteler, Lancet Neurology 2006

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Parkinson’s Disease (PD): Cardinal Features and Clinical Manifestations

Motor Signs

• Bradykinesia

• Tremor at rest

• Rigidity

• Postural instability

Clinical Manifestations

• Decreased arm swing

• Hypomimia

• Hypophonia

• Micrographia

Jankovic J. Handbook of Parkinson’s Disease, 4th ed. 2007:49-76. Jankovic J. J Neurol Neurosurg Psychiatry. 2008;79:368-376.

Morgan J et al. Handbook of Parkinson’s Disease 4th ed, 2007:29-47.

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Nonmotor Symptoms Play an Important Role in Clinical Manifestations of PD

• Anxiety

• Constipation*

• Depression*

• Dementia

• Drooling

• Excessive daytime sleepiness

• Fatigue *

• Hyperhidrosis

• Olfactory dysfunction*

• Orthostatic hypotension

• Pain

• Psychosis

• REM sleep behavior disorder (RBD)*

• Sexual dysfunction

• Urinary urgency

*Although nonmotor symptoms occur throughout the course of PD, certain nonmotor

symptoms are considered “premotor” because onset may precede the emergence of motor

symptoms by years

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Parkinson’s Disease Treatment: Continuum of Interventions for Motor Symptoms

Modified from Giroux, ML et al. Cleveland Clinic Foundation 2005

Signs of levodopa “wearing-off”

Dyskinesia, “On-Off”

Motor Fluctuations

Postural Instability, Freezing, Falls, Dementia

DBS

Mild Moderate Severe

Levo-dopa, MAO inhibitors, COMT inhibitors, DA agonists

Treatment

Patient Symptoms

Disease Severity

MAO inhibitors

DA Agonists

DBS plus Levo-dopa, or DA agonist, ACH esterase inhibitor Duopa dopamine Pump

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TREATMENT GOALS

• The main goal is to improve quality of life- symptomatic.

• Ideally, treatments would be “neuroprotective” or “neuroregenerative”

• Currently available treatments – medical, surgical, and non-pharmacological – are very effective

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Physical Activity and Nutrition

• Aerobic activity-at least 30 min (Biking, Running, Tai chi, Dancing, Strength training,

Stretching, Yoga, Swimming, Boxing) • Associated with better cognitive and motor scores and with longevity

• Vitamin B12 and D3 deficiency

• Uric acid levels in men-major role in neuroprotection.

• Eating a fiber-rich diet with plenty of fluids; BEST Diet – Mediterranean Diet

• Physical & Occupational Therapy and Speech/Voice Therapy

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Medications • Dopamine:

Carbidopa/levodopa (Sinemet, Sinemet CR, parcopa)

Levodopa/carbidopa/entacopone (Stalevo)

Rytary

Duodopa

• Dopamine agonists – pramipexole (Mirapex), ropinirole

(Requip), bromocriptine (Parlodel), apomorphine (Apokyn),

rotigotine patch (Neupro)

• MAO-B inhibitors – selegiline (Eldepryl, Zelapar), rasagiline

(Azilect)

• COMT inhibitors – entacapone (Comtan), tolcapone (Tasmar)

• Amantadine (Symmetrel)

• Anticholinergics – trihexyphenidyl (Artane), benztropine

(Cogentin)

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When Should DBS Therapy be Considered?

• When, despite optimized pharmacotherapy, your patient experiences troubling motor symptoms, which may include:

Troubling dyskinesia

Motor fluctuations

Refractory tremor

Wearing off –Marked medication intolerance

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Deep Brain Stimulation

Neuromodulation therapy

Reversible

Minimally invasive

Stereotactically implanted electrode delivers high-frequency stimulation

>140,000 patients treated with DBS Therapy worldwide

>2000 scientific articles published on DBS

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Targeting

Imaging

Stereotactic targeting

Physiologic targeting - microelectrode recording & stimulation)

Facilitates programming

of optimal parameters

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DBS in PD

• Best predictor of outcome → RESPONSE to LEVODOPA

• Best candidates:

1. Clear diagnosis of idiopathic PD

2. Good and present response to levodopa: Pre-operative ON/OFF evaluation: at least 30 % improvement in motor UPDRS

3. Disabling symptoms, despite optimized pharmacotherapy

4. Motor fluctuations and/or disabling dyskinesias

5. Normal cognition (absence of dementia)

6. Realistic expectations and good family support

7. Access to programming of stimulators

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Poor Candidates for DBS

• Minimal or absent response to levodopa (except tremor)

• Significant cognitive dysfunction

• Untreated depression or other psychiatric disease

• Uncontrolled hypertension or bleeding diathesis

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Expected Outcomes: DBS for PD

With DBS, OFF-medication motor function becomes more like the best pre-op ON-state

OFF time-reduced by 5.2 hours

Dyskinesia -reduced by >75%

Motor fluctuations-lessened

Cardinal motor signs/symptoms improved

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DBS vs. Best Medical Therapy and Survival

DBS Best Medical Treatment

Mean Gain of “good” ON time in hours per day

4.6 hours “0” hours

Clinically meaningful motor function improvement

71% 32%

Quality of Life PDQ-39 scores

Improved No change

Neurocognitive performance

Mild decrement

Slightly improved

Weaver, et al JAMA, Jan 2009, (1)301:63-73

Ngoga et al ,JNNP; 2013

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Results of DBS Surgery for PD • GPi DBS

• Reduces contralateral tremor, rigidity, bradykinesia, dyskinesia, & dystonia

• Improves gait & balance

• Medication reduction- minimal

• STN DBS

• Reduces contralateral tremor, rigidity, bradykinesia, & gait/balance dysfunction

• May exacerbate dyskinesia acutely

• Substantial medication reduction common

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Potential Complications and Risks

• Surgery related (UTMOVE team less than 2%)

– Hemorrhage (inherent in any stereotactic procedure)

– Transient confusion

– Infection (typically occurs at neurostimulator site in chest when it does occur)

• Stimulation related

– Usually can be minimized or eliminated by adjusting stimulation settings

– Reversible paresthesia, dysarthria, muscle contraction.

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Components of Successful DBS Therapy

Appropriate patient selection

Accurate surgical DBS lead placement

Optimal DBS programming

Medication management in concert with DBS

Management of side effects

Patient education and support

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DBS : What the Future Holds

• DBS will be increasingly used for movement disorders patients

• Trends toward earlier intervention

4-7 years after diagnosis

**February 2016- FDA approved intervention with DBS in PD at 4 years

EARLY STIM clinical study, NEJM 2013 UTMOVE

Provide comprehensive clinical care for regional, state, national and international communities.

Largest movement disorders program in Texas and Louisiana with the most active DBS program in Texas with an average of 4-8 Stage I cases per month

Deep Brain Stimulation with Microelectrode Recording (MER) facilitates excellent programming outcomes

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Over 5000 patients seen per year

Multiple research projects on Essential tremor, Parkinsonism,

Huntington’s disease and Dystonia.

Partner with HAPS & TIRR - social services, support groups and

physical therapies.

Locations: UT MOVE UTP Clinic, Quentin Mease -Community Hospital ,UT MOVE– The Woodlands

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Our Physicians: • Mya Schiess, M.D. • Erin Furr-Stimming, M.D. • Raja Mehanna, MD • Allison Boyle, MD • Al Fenoy, MD (Neurosurgery) UT MOVE Clinic Direct Tel: 832-325-7080 or 832-325-7081 UT Professional Building Adult Neurology Clinic 6410 Fannin Suite 1014 Houston, Texas 77030

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Navigating the DBS Experience and Procedure

• Key contact person for questions, answers, scheduling post- op programming

• Mike Almaguer, RN at 832 325-7160

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