Deep Brain Stimulation for
Movement Disorders
Esmiralda Henderson, M.D.
Mercy Medical Center
Neurological Surgery
Disclosures
• No financial relationships.
• Investigational treatments will be discussed.
Overview
• Deep brain stimulation (DBS) uses a surgically
implanted medical device, similar to a cardiac
pacemaker, to deliver a carefully controlled
electrical stimulation to precisely targeted
areas in the brain.
• It works by electrically stimulating specific
structures in a neural circuit that is involved in
producing unwanted symptoms.
Overview
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Parkinson’s Disease – FDA approved, 2002.
Essential Tremor – FDA approved, 1997.
Dystonia – FDA approved (HDE), 2003
Other conditions: Chronic pain, OCD (HDE,
2009), depression, Tourette's disease,
Alzheimer’s, obesity, addiction, cluster
headache, secondary tremors.
Neuromodulation
Dystonia
Parkinson’s disease
Essential
Tremor
Chronic Migraine *
Chronic Pain
RSD
Failed back
Gastroparesis
Obsessive Compulsive Disorder
Depression
*
Epilepsy *
Bradycardia
Heart Failure
Tachycardia
Angina
Obesity *
Bowel Disorders *
Interstitial Cystitis *
Urinary Incontinence
History of stereotactic surgery
and
deep brain stimulation
Progression
• Understanding that deep brain structures are
involved in the movement disorders.
• Destruction of structures.
• Stereotactic focused destructions.
• Delineating the circuits involved in the
disease.
• Focused deep brain stimulation.
Meyer’s approach to the basal ganglia. (Meyers R. The surgery of the hyperkinetic disorders. In:
Vinken PJ, Bruyn GW, eds. Diseases of the Basal Ganglia. New York: North-Holland Publishing,
1968: 844-878.)
The Horsley-Clarke Stereotactic Device was first reported in Brain (31:45-124, 1908)
First DBS implants
• 1975 – fist chronic therapy
via DBS by Russian
neuroscientist Natalia
Bekhtereva.
• Stimulation at high
frequency inhibited activity
of the tremor causing area
of the brain. Effects were
similar effects to the
ablation with reversibility of
the therapy.
Pacemakers:
1957
Model 5800
1957
History
• 1980’s - deep brain stimulation for tremor is
systematically used in France and popularized
by Dr. Alim Benabid.
Present
• > 100,000 DBS implants worldwide.
• >7000 published articles on DBS.
• Well established safety profile for three
decades.
• Technological evolution.
• Therapy that is reversible and adjustable.
A
B
D
C
A
B
D
C
DBS
electrical stimulation
A
B
D
C
Candidate Selection via
Multidisciplinary Approach
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Neurologist
Movement Disorder Neurologist
Neurosurgeon
Neuropsychiatrist/psychologist
Neurophysiologist
PM&R
Specialized OR suite
Parkinson’s Disease
• Neurodegenerative disorders that begins with the
destruction of substantia nigra pars compacta.
• Progressive loss of dopamine results in abnormal
electrical activity in the brain.
• Medications help, but many of patients become
treatment resistant over time.
• 50,000-60,000 new cases each year.
• Over one million people who currently have PD.
Parkinson’s Disease
• Motor symptoms:
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Tremor (resting)
Rigidity (stiffness)
Akinesia/bradykinesia (absence/slowness of movements
Gait shuffling, freezing.
Postural instability.
• Non-motor symptoms: dementia, impulsivity,
depression – late stages.
Patient Selection –Parkinson’s Disease
• Idiopathic PD
• Bradykinesia, tremor, rigidity – maximized on
medical management with poor symptomatic
control.
• Medication response: >30%.
• Significant tremor that never responded to
medications.
• ON/OFF fluctuations and bothersome
dyskinesias.
Disease Severity
Mild
Signs of levodopa
“wearing-off”
Patient Symptoms
Treatment
Moderate
Agonists
Levodopa, COMT
inhibitors, others
Severe
Dyskinesia,
“On-Off”
Motor
Fluctuations
DBS
Postural Instability, Freezing,
Falls, Dementia
Target
Hamani C et al. Brain 2004;127:4-20
Essential tremor
• Very common.
• Prevalence – 0.4-5.5%, in population over 65 –
up to 14%.
• Often under-diagnosed and undertreated.
• Progressive.
• 50% of patients fail medical management.
Essential Tremor
• It is characterized by an action or postural tremor
in the frequency range of 4 to 12 Hz.
• Alcohol transiently diminishes tremor amplitude
in 50% to 90% of cases, although this may worsen
after the effect of alcohol has worn off.
• The location varies. Approximately 90% of
patients have tremor in their upper extremities,
30% have a head tremor, 20% have a voice
tremor, 10% have a face or jaw tremor, and 10%
of ET patients may have a lower limb tremor.
Essential tremor subtypes
• Hereditary ET, for patients who fulfill consensus criteria for
definite or classic ET and also have a family of at least one
affected relative in the immediate family. The onset of
tremor in the patient and the family member must occur
prior to age 65 years.
• Sporadic ET, for patients who fulfill the consensus criteria
for definite or classic ET, but do not have an immediate
family member with ET, and whose age at onset of ET is
younger than 65 years.
• Senile ET, for patients who have definite or classic ET
according to consensus criteria, but who develop ET at or
after the age of 65 years. Patients may or may not have a
family history of ET.
Patient Selection – Essential Tremor
• Proper diagnosis.
• Tremor that is maximized on medical
management with poor symptomatic control.
• Medications are contraindicated or side
effects are intolerable.
• Tremor is severe enough to interfere with
ADLs, job duties, social interactions.
ET DBS
Target
Target: VIM
Axial View
DYSTONIA
• A syndrome of spontaneous sustained muscle
contractions, with frequently twisting and
repetitive movements, or abnormal postures.
• Third most common movement disorder
• Repetitive patterned movements
• Often exacerbated by voluntary motor activity
• Genetic component
– Autosomal dominant mutation
– DYT genes
Patient Selection - Dystonia
• Primary and secondary dystonia.
• Failed conservative management.
• Functional incapacitation.
• Children included.
General considerations
in patient selection
• Stable medical co-morbidities.
• Stable cognition and psychiatric illnesses.
• Good social support system and commitment
to programming sessions.
• No structural lesions.
Target
Hamani C et al. Brain 2004;127:4-20
Procedural Overview
In a frame-based system, the stereotactic arc is attached to the base of the frame.
MACHADO A G et al. Cleveland Clinic Journal of Medicine
2012;79:S19-S24
©2012 by Cleveland Clinic
Post Operative Course and Recovery
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Programming takes place 4
weeks after the original
surgery.
Lesion effect.
Patient has his/her own
programmer to chose different
programs and turn device on
and off.
Patients and caregivers are
educated on device use.
Outcomes – Parkinson’s Disease
• Level I evidence demonstrating efficacy
DBS Improvement in PD
“ON” Time Without Dyskinesias Improves from 27% to 74%
19%
27%
7%
49%
74%*
23%
Before Surgery
(n=96)
‘ON’ with Dyskinesia
6 Months After Surgery
Bilateral STN Activa® Implant
(n=91)
‘ON’ without Dyskinesia
‘OFF’
* The Deep-Brain Stimulation for Parkinson’s Disease Study Group. Deep-brain stimulation of the subthalamic nucleus for the
pars interna of the globus pallidus in Parkinson’s disease. N Eng J Med. 2001;345:956-63.
Medtronic DBS Therapy Clinical Summary, 2009
PD Motor Symptoms Improvement
Maintained After 5 Years
• In a 5-year study, DBS significantly improved OFF-medication
assessments of tremor, rigidity, and akinesia/bradykinesia
OFF-Medication Motor Score Improvements*
6-month
1-year
3 years
5 years
Tremor
79%
75%
83%
75%
Rigidity
58%
73%
74%
71%
Akinesia
42%
63%
52%
49%
Essential Tremor Outcomes
• Hand/arm tremor – 80% of patients have near
complete tremor relief. 20% have significant relief of
the tremor.
• Head/neck/trunk/voice tremor – 50-60% relief of the
tremor. May require bilateral implant.
• Follow-ups of several years are established with good
durability of the efficacy.
• If disease progresses, then stimulation may be easily
adjusted.
Dystonia DBS
• Improvement is not immediate – few months.
• Primary/Idiopathic-best results:
• DYT-1, generalized – 74%
• Cervical, when it comes to focal dystonia.
• Appendicular dystonia responds better than one with axial symptoms.
• Secondary-inconsistent results:
• Structural lesions – less responsive
• Tardive dystonia are exceptions – best responder
• Outcome 23-91% improvement.
Adverse Reactions
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Every surgery has risks.
Infection is most common: 3-4%.
Major complications <1%.
Hardware malfunctions.
Frontiers
• Same disease-new targets: pedunculopontine
nucleus (PPN) DBS for gait abnormalities in
PD.
• New technology – Medtronic Activa PC+S
• New movement disorders targeted –
Tourette's disease.
• MRI safety clinical studies.
Conclusion
• Multidisciplinary approach is essential.
• Deep brain stimulation provides significant
symptomatic relief and improves quality of life
in well selected patients with certain
movement disorders.
• Thank You!