Transcript Functional Neurosurgery

Functional Neurosurgery
Managing Parkinson’s Disease with
Deep Brain Stimulation
Ravi Vissapragada
Case Introduction
• P.R: 63 yo male suffering with Parkinson’s
disease for 15 years attending Neurology for
worsening Parkinson’s disease and drug
related dyskinesia
• Seen in clinic for a Deep Brain Stimulation
procedure consult
Presenting Complaint
• P.R signs of parkisonism began 15 years ago
• First noted in gait examination in a diminished arm swing noted on
the left side
• P.R started on Sinemet (carbidopa-levodopa)
• Also treated with Mirapex (Pramipexole)
• Needed increasing doses and tightened dose intervals, leading to
prominent dyskinesia
• Decreasing Sinemet and Mirapex worsened the effect of the
disease and was not tolerable
History
• Drugs:
– Amantadine, Carbidopa-Levodopa, OxycodoneAcetaminophen, Parsitan, Pramipexole, Simvastatin,
Sotalol, Zolpidem, Aspirin, Docusate
• Allergies:
– Atorvastatin (Lipitor)
• PMHx
– Diabetes Mellitus Type II
– Coronary Artery Disease
– Paroxysmal Atrial Fibrillation
• PSHx
– Lumbar fusion
• FHx
– Heart disease
• SHx
– Retired gentleman, lives with wife
UPDRS
• Unified Parkinson’s Disease Rating Scale (UPDRS)
motor score off the medication was 22 and on
medication was 6
– Higher score indicates more disability
– Highest motor score = 108
– 22 = Minimal to mild disability overall with moderate
disability in some areas
Examination:
• Vitals:
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To – 97.4
BP – 148/86
HR – 68
RR – 16
SaO2 – 95% on 2L
• General inspection:
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Appearing well
Oriented to time and place
Language fluent
Noticeably cervical and upper
extremity dyskinesias
• Neurological Exam:
– Extraocular movements intact,
without nystagmus. Gaze midline,
without roving eyemovements
– Sensation to light touch intact and
symmetric in all divisions of face
bilaterally, without numbness
– Face symmetric, no weakness of
facial musculature
– Tongue midline. Extends without
fasciculations
– Palate elevates symmetrically
– Shoulders elevate 5/5 bilaterally
– Sensory: Sensation to light touch
– Motor: No drift, No asteryxis
– Mild rigidity in all limbs
– Full strength bilaterally
– Reflexes = 2+
– Coordination intact
Laboratory Results
• Blood work:
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Hb: 13.9
RBC: 4.79
Hct: 43.4
MCV: 91
WBC: 5.8
Differential:
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Neutrophils: 65.9%
Lymphocytes: 25.5%
Monocytes: 4.9%
Eosinophils: 2.8%
Basophils: 0.8%
• Coagulation:
– Plt Ct: 209
– PT/PTT were not obtained day
of procedure, but were
normal earlier
• Renal Function:
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Urea: 12
Creatinine: 0.7
Na+: 141
K+: 4.1
Cl-: 105
HCO3: 26
Anion gap: 14
• Glucose: 113
Coronal View of Subthalamic Nuclei
Implanted Micro-electrodes before and after surgery
Parkinson’s Disease
Mohammed Ali and Micheal J. Fox
http://medicaltechnologyavenue.blogspot.com/2008/12/parkinson-twitch.html
Parkinson’s Disease
• Type of movement disorder
• Characterized by:
– Bradykinesia
– Rigidity
– Tremors
• Pathophysiology:
– Degeneration of dominergic cells in the pars compacta of substantia
nigra
– Projects to the striatum to participate in the Direct/Indirect Pathway
Cortex
Indirect
Glutamate
Globus Pallidus
(ext. segment)
GABA/Enkephalin
Striatum
(Ach)
GABA/
Substance P
Direct
GABA
?
Subthalamic
Nucleus
Glutamate
Globus Pallidus
(int. segment)
Dopamine
Substantia Nigra
Pars Compacta
Substantia Nigra
Pars Reticulata
GABA
Thalamus
VA, VL
Legend
Excitatory
Inhibitory
Net effect:
Inhibitory
Supplementary
Motor Area
Net effect:
Excitatory
Guidelines for Treatment of Parkinson’s DiseaseJankovic and Aguilar.
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Ensure correct diagnosis
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Determine level of motor, mental, sensory, autonomic, and other impairments
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Educate the patient about the disease and importance of mental and motor
activity
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Consider putative neuroprotective agent(s)
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Select the most appropriate symptomatic therapy, targeted to the most
troublesome symptoms
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Consider surgery (Deep Brain Stimulation) in patient who are levodopa-responsive
but their levodopa-related motor complications cannot be managed adequately
with medication adjustments
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Therapy must be customized and tailored to the individual needs of the patient
Deep Brain Stimulation
• Surgical procedure to implant device to stimulate subthalamic
nucleus in the basal ganglia
• Applications:
– Parkinson’s disease
– Dystonia
– Essential Tremor
– Major Depression
– Tourette’s Syndrome
http://blog.bioethics.net/2009/02/dbs-for-ocd-omg/
Deep Brain Stimulation in Parkinson’s
Disease
• Indications:
– Refractory to medical therapy after trial with multiple agents
– Patients with levodopa induced dyskinesias
– Patients suffering primarily from rigidity and bradykinesia
• Contraindications:
– Significant dementia
• DBS noted to cause cognitive impairment
– Increased risk of intracerebral hemorrhage
• Coagulopathy, hypertension, anti-platalet therapy that cannot be withheld
– Ipsilateral hemianopsia: risk of contralateral optic nerve injury
– Age > 85 years
– Non-idiopathic Parkinsonism
• Shy-Drager, PSNP, OPCA, Arteriosclerotic Parkinsonism (lacunar infarcts)
Deep Brain Stimulation Procedure
• Done in 2 stages
– Stage 1:
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Stereotactic frame put on patient (under sedation)
Stereotactic MRI
Trajectory identified
Burr Hole made
Dura dissected
Probe passed down
Testing begins after passing the probe down to subthalamic nuclei
– Monitoring by sending electrical impulses through the tip of the probe to
identify the correct location to place micro-electrode
– Also monitoring by testing clinical effects of stimulation
• Electrode placed and lead left under the scalp
• Repeated on contralateral side if bilateral DBS
– Stage 2:
• Attaching the lead to the battery
Potential Complications
• Intracerebral Hemorrhage: 1%
• Wound Infection: 3-5%
• Lead Fracture
• Battery Failure
Literature Overview
Bilateral Deep Brain Stimulation vs. Best Medical Therapy
Weaver et al. 2009
• Compares 6-month outcomes for patients with PD who received DBS
or the best medical therapy
• RCT of 255 patients with PD (Hoehn and Yahr stage ≥ 2*) stratified by
age and study site**
• Bilateral DBS of subthalamic nuclei or globus pallidus
• Best medical therapy: actively managed by movement disorder
neurologists
• Measuring outcome:
– Time spent in the “on” state without troubling dyskinesia
– “On” state defined as “good motor control with unimpeded motor function”
– Measured primarily using motor diaries, motor function, QoL, cognitive
function, and adverse events
*Hoehn and Yahr stage ≥ 2: Bilateral symptoms, minimal disability, posture and gait affected
** Patient Selection: Stage 2 or greater off medication, but have symptoms (motor fluctuations and dyskinesias) on medications, must be
responsive to Levodopa, experince ≥ 3 hrs/24 hrs, were receiving medical therapy for 1 month or longer, aged > 21yrs
Exclusion criteria: atypical syndromes, previous surgery for PD, surgical contraindications, active alcohol or drug abuse, dementia, or pregnancy
Results
A Randomized trial of Deep Brain Stimulation for Parkinson’s
Disease
Deuschl et al. 2006
• European study
• Randomized-pairs trial of 156 patients with advanced Parkinson’s
and severe motor symptoms
• Deep Brain Stimulation vs. Medical Management
• Measured QoL from baseline to six months
– PDQ-39 (Parkinson’s Questionnaire)
– UPDRS part III
• Exclusion criteria
– Age < 75, no dementia/psychiatric illnesses, symptoms must be limiting
daily functioning
• Optimized medical care provided by Neurologists specializing in
movement disorders
• Bilateral Deep brain stimulation of subthalamic nucleus using
stereotactic imaging and standard microelectrode sampling
techniques
Results
Expectation and the Placebo Effect in Parkinson’s Disease
Patients with Subthalamic Nucleus Deep Brain Stimulation
Mercado et al.
• 10 patients with idiopathic Parkinson’s Disease and bilateral subthalamic
nucleus deep brain stimulation procedures selected
• UPDRS III (motor) Scores obtained in 4 situations (off medication):
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Stimulus OFF: Patient aware
Stimulus OFF: Patient blind
Stimulus ON: Patient aware
Stimulus ON: Patient blind
• Results:
– OFF stimulus: patients who were aware had higher UPDRS
– ON stimulus: patients who were aware had lower UPDRS scores
Five-Year Follow up of Bilateral Stimulation of the
Subthalamic Nucleus in Advanced Parkinson’s Disease
Krack et. al
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5 year prospective study
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49 consecutive patients with bilateral stimulation of subthalamic nucleus
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Assessed at 1 year, 3 years, 5 years
– On medication (levodopa)
– Off medication
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UPDRS III used to motor function scores
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Results after 5 years:
– Motor function improved greatly off medication
– Dyskinesia improved markedly on medication
– Worsening akinesia, speech, postural stability, freezing of gait, and cognitive
function
Bottom Line
• Deep Brain Stimulation: Good or Bad??
– Factors:
• Patient
– Age, preference, symptoms, surgically fit
• Multidisciplinary team input
• Facing the facts:
• Improvement of all symptoms in the first year of DBS
• Including akinesia, gait, speech, postural stability
• Patients are usually elderly folk with multiple comorbidities and
debilitating symptoms
• Thus 1 year of symptomatic relief is a significant improvement
Post-Operative Details
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Surgery was well tolerated
No pain except at surgical sites
No confusion reported (by wife and daughter)
Exam:
– Awake, alert, and oriented to time and place 3.5 hrs post-surgery
– Vitals:
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To – 97.4
BP – 148/86
HR – 68
RR – 16
SaO2 – 95% on 2L
• No neurologic deficit noted
• Mild rigidity and bradykinesia noted
• No dyskinesia
Thank you
Acknowledgements
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Dr. Papavassiliou
Dr. Fred Lam
Dr. Andrey Zinchuk
Dr. Chen
Bibliography
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Rodriguez RL. Pearls in Patient Selection for Deep Brain Stimulation. Neurologist. 2007 Sep;13(5):253-60
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M. S. Greenberg.: Surgical Treatment of Parkinson’s Disease. Handbook of Neurosusrgery 6th Ed., 15.2:365-6,
2006
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Deuschl et al. A Randomized Trial of Deep Brain Stimulation for Parkinson’s Disease. N Engl J Med 2006;355:89690
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Jankovic, Aguilar. Current approaches to the treatment of Parkinson’s Disease. Neuropsychiatric Disease and
Treatment 2008:4 (4) 743-75
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Weaver et al. Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson’s
Disease: A Randomized Controlled Trial. JAMA. 2009;301(1):63-73
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Temel. Blokland.The functional role of the subthalamic nucleus in cognitive and limbic circuits. Progress in
Neurobiology 76 (2005) 393-413.
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Mercado et al. Expectation and the Placebo Effect in Parkinson’s Disease Patients With Subthalamic Nucleus Deep
Brain Stimulation. Movement Disorders. 21 (2006). 1457-1461.
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Krack et al. Five year Follow-up of Bilateral Stimulation of Subthalamic Nucleus in Advanced Parkinson’s Disease.