Transcript Deep Brain Stimulation - Welcome to the North American

Deep
Brain
Stimulation
Punit Agrawal, DO
Movement Disorder Division
Department of Neurology
The Ohio State University
• This lecture reviews
DBS patient selection
and management with
a focus on approved
FDA indication for
Movement Disorders
– No conflicts of
interests to disclose
FDA Approved Indications
– Essential Tremor
• FDA approved in 1997
– Parkinson’s disease
• FDA approved in 2002
– Dystonia
• FDA approved (HDE*) in 2003
– Obsessive Compulsive Disorder
• FDA approved (HDE**) in 2009
• Medicare and Insurance reimbursed for FDA approved indications
*Humanitarian Device: Authorized by Federal (U.S.A) 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.
**Humanitarian Device: Authorized by Federal (U.S.A) law for use as an adjunct to medications and as alternative to anterior capsulotomy for treatment of
chronic, severe, treatment-resistant obsessive-compulsive disorder (OCD) in adult patients who have failed at least three selective serotonin reuptake
inhibitors (SSRIs). The effectiveness of this device for this use has not been demonstrated.
• Offers hope to severely impaired patients when symptoms are
intractable despite optimal medication and other available
therapies.
• > 22 years of safety
• > 80,000 DBS Implants worldwide
• >3000 published articles on DBS
• With proper patient selection, there is improvement seen with:
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Standard scales/measures of disease
Quality of life measures
Co-morbid conditions
Medication intake
Chronic care costs
DBS Target Sites for Movement
Disorders
Vim Thalamus:
Essential Tremor
Subthalamic Nucleus:
Parkinson’s disease
and Dystonia
Globus Pallidus:
Parkinson’s disease
and Dystonia
Movement Disorders Patient
Evaluation
– Movement Disorder Neurology
• Evaluate medications and disease
– Levodopa ON-OFF assessment in Parkinson’s
disease
– Neurosurgery
• Discuss surgery, implantable devices, risks
– MRI of the brain
– Neuropsychological testing
– Review and Discussion at Patient Management
Meeting
– Team recommendation
Approach to Improve Outcomes
• Multidisciplinary Team:
– Neurology, neurosurgery, psychiatry, psychology,
physical medicine and rehabilitation, neuroradiology,
neuroanesthesia, PT/OT/ST, social worker/case
manager.
• Proper Patient Selection
• Patient screening for appropriate candidates for DBS therapy
and education
• Realistic and proper expectations from DBS therapy
• Psychosocial assessment
Poor Candidates for DBS
• Significant dementia or cognitive impairment
– Neuropsychological compromise
• Untreated depression, anxiety, psychosis, or other co-morbid psychiatric
illness
• Unable to cooperate during surgical procedure
• Unable to cooperate during programming visits
• Unrealistic expectations of outcomes
• Co-existing medical problems that significantly increase risks of surgery
– Uncontrolled heart disease, lung disease, cerebrovascular disease,
uncontrolled hypertension, or diabetes.
• Significant structural abnormalities detected by brain MRI that would pose
higher risk of brain surgery
• Additional features suggesting poor candidates for parkinsonism
– Minimal or absent response to levodopa
– Atypical Parkinsonian syndromes
DBS for Tremor
• Severe debilitating medication refractory
tremor
Propranolol
Neurontin
Primidone
Keppra
Anticholinergic PD medications
• Resting Tremor > Postural Tremor > Intention
Tremor
• Expectations: Improve quality of life and that
it may not completely eliminate all tremor
• Target: VIM thalamic DBS
Tremor Outcomes with VIM Thalamic
DBS
- Essential tremor: 60-80% improvement
- MS, traumatic brain injury and cerebellar tremor: 50% improvement
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
40-50%
50%
PreOP
PostOP
>80% >75%
PD
ET
MS
PostTraumatic
DBS for Parkinson’s Disease
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Multiple prospective randomized controlled trials have
demonstrated benefits
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Tremor
Rigidity and bradykinesia similar to levodopa
Reduced motor fluctuations including less dyskinesia and
improved “ON” time.
Reduction in medications
Reduction in maintenance cost of disease
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10-20% of individuals with Parkinson’s disease may be
candidates for DBS therapy*
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Brain Targets: STN / GPi / VIM
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Aspects important with regards to patient education and
expectations
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*AAN
Not a cure and does not stop disease progression.
Does not reverse disease.
Does not prevent dementia.
May be minimally helpful for gait trouble, imbalance, or posture
changes.
Excluding tremor, minimal help of symptoms not responsive to
levodopa.
Does not help non-motor symptoms.
Guideline Summary for Patients and their Families: Medical and Surgical Treatment for
Motor Fluctuations and Dyskinesia in Parkinson Disease, 2006
PD with DBS Off verse On
Good PD Candidates
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Clear diagnosis of idiopathic Parkinson’s disease
• Atypical Parkinson’s or Parkinson’s like syndromes do not improve
with surgery
Good response to levodopa with levodopa challenge showing at least 33%
improved UPDRS motor score
Issues include one or more of the following
– 1) Significant Motor fluctuations and/or disabling dyskinesia
– 2) Disabling tremor despite optimal medication treatment:
Levodopa
Selegiline/rasagiline
Amantadine
Ropinirole/Pramipexole
Benzodiazepines
Parsitan/benztropine/trihexyphenidyl
– 3) Medication Intolerance
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Stable cognition (absence of significant dementia)
Realistic expectations and good family support
No co-morbid psychiatric/behavioral problem
Greater than 5 years of disease duration
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.
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%
*Results for STN
Economic Benefits of DBS
Cost Analysis in PD: Multiple comparisons of medical resource use before and
after DBS show that DBS significantly reduces the cost of care
DBS reduces the daily dosage of levodopa and dopamine agonists,
significantly reducing drug costs by 12 months (Spottke et al, 2002)
DBS for Dystonia
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Most effective for primary dystonia
• Generalized, segmental, hemi-dystonia, and focal dystonia including cervical
dystonia
– DYT -1
• Secondary dystonia such as those caused by trauma or metabolic disorders can be
less responsive to DBS therapy with inconsistent results
– Those with structural lesions can worsen
– Tardive dystonia are exceptions with often good response
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Significantly impairment of normal activities and quality of life
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Failed maximal combinations of medication trials:
- Muscle relaxants
- Benzodiazepines
- Anticholinergics
- Levodopa
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Failure of botulinum toxin therapy or the dystonia affects too large of an area for this modality
of treatment
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Ages 7 and older
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Targets
– Globus pallidus internus (Gpi)
– Thalamus
• Vop,Voa
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Outcome 23-91% improvement
•Double blind, class I study
•40 pts with GPi DBS randomized to
Stimulation or Sham for 3 months
•At 3 months, all patients received open label
active stimulation until the 6-month outcome
measure
•Stim ON: 15.8±14.1points
Sham: 1.4±3.8 points (P<0.001)
•BFMDRS score reduction
OCD Candidates for DBS
– The most severely disabled patients
– 5 years of disease
– Multiple medication and behavioral therapy
resistant
– Predominant contamination behaviors
– Requires multidisciplinary team for patient
selection including psychiatry, psychology,
neuropsychology, neurosurgery, and ethics.
DBS for Obsessive Compulsive Disorder
60% of Patients with severe end stage OCD were responders with DBS
Improvement in OCD scores (YBOCS), Quality of life (GAF)
And depression (HAM-D)-------Led to new indication for depression
FDA approval US-HDE 2009
DBS for OCD
• Clinical Trial:
– The most severely disabled patients
– 5 years of disease, multiple medication resistant, 20 inpatient admissions
• Results-- 60% of patients were significantly
improved
– Decreased obsessions, compulsion, improved functioning,
– Improved self care, social and occupational functioning,
Quality of life, functioning, working, dating, getting
married, living independently
Surgical Procedure
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Brain imaging
Computerized guidance
Micro-robotics
Electrical recording of
brain function
mm precision
Direct targeting
RN
STN
SNr
RN
SNr
STN
Anatomical Atlas morphing and Targeting
Physiological Mapping
• Microelectrode recording
(MER)
• microstimulation
• Macrostimulation with DBS
electrode
Intraoperative mapping
Intra-operative DBS Testing
Potential Complications/Risks
– Hemorrhage (inherent in any stereotactic procedure);
may be silent or symptomatic
– Transient confusion
– Infection (typically occurs at neurostimulator site
in chest when it does occur)
– Device related
– Stimulation related
• Usually can be minimized or eliminated
by adjusting stimulation settings
• Reversible paresthesia, dysarthria,
muscle contraction
Overview of
Programming
• Anode/Cathode
• Variables
– Contacts – 4 for each
electrode
– Amplitude
– Rate
– Pulse Width
– Monopolar vs Bipolar
– Constant Current vs
Constant Voltage
• Soft Start
• Impedance
• Battery Status
DBS Lead Electrode Selection
0
1
2
3
Lead
Electrodes
3
2
1
0
off
(+) positive
off
off
(-)
off
Unipolar
* The negative electrode exerts the therapeutic effect
Bipolar
3
2
1
0
off
(+)
(-)
off
Monopolar vs Bipolar
• Bipolar stimulation can limit the spread and is
beneficial to shaping field of stimulation
Stimulation Parameters
Pulse Width
(sec)
duration of each stimulus
Amplitude
(Volts)
intensity of stimulation
Rate
(Hertz)
number of pulses
per second
Movement Disorder DBS
Management
• DBS programming goal
– Deliver the therapy to the brain target of interest with avoiding
stimulation of surrounding structures
• Typically, initial programming of DBS is 2 - 4 weeks after DBS
electrode implant
• Subsequent programming can be every 2-8 weeks for the first 3
months, and then every 3-6 months thereafter
• Commonly takes 6 months to obtain the best settings
• Many patients will require concurrent medication adjustments
Systematic Approach: Initial
Programming
• Identify patients prominent symptoms and review
expectation of DBS.
• Inspect and palpate hardware
• Monopolar review – should be done with every initial
programming and when side effects suspected:
– With constant rate (130) and pulse width (90) assess individual
contacts with monopolar settings with regards to threshold of
stimulation and apparent improvement of symptoms while slowly
increasing the amplitude
• Useful to identify anatomy and position within the target nuclei
• Useful for future programming sessions and trouble shooting
• Trial of bipolar vs monopolar if low threshold
• Check impedances and battery
• Educate patient on use of patient programmer and/or
recharger if applicable
Systematic Approach: Subsequent
DBS Programming
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Identify any problems or side effects related to DBS
Inspect and palpate hardware
Check impedances, battery and for activations
Adjust DBS parameters: common strategy is to make one parameter
change with little adjustments to other parameters.
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Adjust amplitude with little or no change in rate or pulse width
Adjust rate with little or no change to amplitude or pulse width
Adjust pulse width with little or no change to amplitude or rate
Change bipolar and assess for threshold with resetting at tolerable level
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For PD, best to program with patients in the “Off” state
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If PD, have patient take typical dose of PD medications and wait for
medications to have taken effect
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Adjust medication if indicated
DBS Common Settings
• Settings for different indications and target
PW (µs)
Rate (Hz)
STN – PD
60-90
130-185
GPi - PD
90-120
130-185
VIM Tremor
60-90
100-185
GPi Dystonia
120-450
60-145
DBS Problem Solving
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No improvement
Contracture/slurred speech
Review anatomical location of
Persistent numbness
stimulation with monopolar review
Double vision
Visual disturbances
Dyskinesia
Autonomic symptoms
Regional STN Anatomy
– Target is the dorsal-lateral
portion of STN
• Medial lemniscus – posterior
– Stimulation can cause
intolerable paresthesia
• Internal Capsule – anterior,
lateral and ventral
– Stimulation can cause tonic
contracture
• CN III – medial caudal
– Stimulation can cause diplopia
• Hypothalamus – medial rostral
– Stimulation can cause
autonomic symptoms
• Ventral Medial STN
– Stimulation can cause mood
changes
IC = internal capsule
STN = subthalamic nucleus
ML = medial lemniscus
RN = red nucleus
Regional VIM Anatomy
– Internal Capsule – ventral
and lateral
• Stimulation can cause tonic
contracture
– Ventral Caudal (Vc)
thalamus (sensory relay) –
posterior
• Stimulation can cause
intolerable paresthesia
– Ventral Oralis Posterior
(Vop) thalamus – anterior
• Stimulation may cause no
effect on tremor
Vo = ventral oral (pallidal relay)
Vim = ventral intermediate
(cerebellar relay)
Vc = ventral caudal (principle
somatosensory nucleus)
IC = internal capsule
Regional GPi Anatomy
• Internal Capsule posterior
– Stimulation can cause
tonic contracture
• Optic Tract – ventral
– Stimulation can cause
visual disturbances
GP = globus pallidus
IC = internal capsule
OT = optic tract
Long term Maintenance
• No MRI other than of the head with use of specific restrictions.
• Avoid activities that cause excessive torque on the neck
• Awareness of electromagnetic fields that can cause DBS devices to
turn on/off.
• Battery drain – monitor battery status
• Watch for signs of skin breakdown or irritation around DBS
hardware, and inspect for signs of disconnections or lead wire
migration
• Check and reset activations with each programming session, and
check impedance levels.
• If concern for device failure, check unit if on/off, number of
activations, battery status, hardware malfunction (imaging), and
impedances