Functional Neurosurgery Managing Parkinson s Disease with

1
Functional Neurosurgery

• Managing Parkinsons Disease with Deep Brain
  Stimulation

Ravi Vissapragada
2
Case Introduction

• P.R 63 yo male suffering with Parkinsons
  disease for 15 years attending Neurology for
  worsening Parkinsons disease and drug related
  dyskinesia
• Seen in clinic for a Deep Brain Stimulation
  procedure consult

3
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

4
History

• Drugs
• Amantadine, Carbidopa-Levodopa,
  Oxycodone-Acetaminophen, 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

5
UPDRS

• Unified Parkinsons 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

6
Examination

• Vitals
• To 97.4
• BP 148/86
• HR 68
• RR 16
• SaO2 95 on 2L
• General inspection
• 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

7
Laboratory Results

• Blood work
• Hb 13.9
• RBC 4.79
• Hct 43.4
• MCV 91
• WBC 5.8
• Differential
• 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
• Urea 12
• Creatinine 0.7
• Na 141
• K 4.1
• Cl- 105
• HCO3 26
• Anion gap 14
• Glucose 113

8
Coronal View of Subthalamic Nuclei
9
(No Transcript)
10
Implanted Micro-electrodes before and after
surgery
11
Parkinsons Disease
http//medicaltechnologyavenue.blogspot.com/2008/1
2/parkinson-twitch.html
12
Parkinsons 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

13
Cortex
Striatum (Ach)
Globus Pallidus (ext. segment)
Substantia Nigra Pars Compacta
?
Subthalamic Nucleus
Thalamus VA, VL
14
Guidelines for Treatment of Parkinsons
Disease-Jankovic and Aguilar.

• Ensure correct diagnosis
• Determine level of motor, mental, sensory,
  autonomic, and other impairments
• Educate the patient about the disease and
  importance of mental and motor activity
• Consider putative neuroprotective agent(s)
• Select the most appropriate symptomatic therapy,
  targeted to the most troublesome symptoms
• Consider surgery (Deep Brain Stimulation) in
  patient who are levodopa-responsive but their
  levodopa-related motor complications cannot be
  managed adequately with medication adjustments
• Therapy must be customized and tailored to the
  individual needs of the patient

15
Deep Brain Stimulation

• Surgical procedure to implant device to stimulate
  subthalamic nucleus in the basal ganglia
• Applications
• Parkinsons disease
• Dystonia
• Essential Tremor
• Major Depression
• Tourettes Syndrome

http//blog.bioethics.net/2009/02/dbs-for-ocd-omg/
16
Deep Brain Stimulation in Parkinsons 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 gt 85 years
• Non-idiopathic Parkinsonism
• Shy-Drager, PSNP, OPCA, Arteriosclerotic
  Parkinsonism (lacunar infarcts)

17
Deep Brain Stimulation Procedure

• Done in 2 stages
• Stage 1
• 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

18
Potential Complications

• Intracerebral Hemorrhage 1
• Wound Infection 3-5
• Lead Fracture
• Battery Failure

19
Literature Overview
20
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 gt 21yrs Exclusion criteria
atypical syndromes, previous surgery for PD,
surgical contraindications, active alcohol or
drug abuse, dementia, or pregnancy
21
Results
22
A Randomized trial of Deep Brain Stimulation for
Parkinsons DiseaseDeuschl et al. 2006

• European study
• Randomized-pairs trial of 156 patients with
  advanced Parkinsons and severe motor symptoms
• Deep Brain Stimulation vs. Medical Management
• Measured QoL from baseline to six months
• PDQ-39 (Parkinsons Questionnaire)
• UPDRS part III
• Exclusion criteria
• Age lt 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

23
Results
24
(No Transcript)
25
Expectation and the Placebo Effect in Parkinsons
Disease Patients with Subthalamic Nucleus Deep
Brain StimulationMercado et al.

• 10 patients with idiopathic Parkinsons Disease
  and bilateral subthalamic nucleus deep brain
  stimulation procedures selected
• UPDRS III (motor) Scores obtained in 4 situations
  (off medication)
• 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

26
Five-Year Follow up of Bilateral Stimulation of
the Subthalamic Nucleus in Advanced Parkinsons
DiseaseKrack et. al

• 5 year prospective study
• 49 consecutive patients with bilateral
  stimulation of subthalamic nucleus
• Assessed at 1 year, 3 years, 5 years
• On medication (levodopa)
• Off medication
• UPDRS III used to motor function scores
• 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

27
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

28
Post-Operative Details

• 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
• 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

29
Thank you
30
Acknowledgements

• Dr. Papavassiliou
• Dr. Fred Lam
• Dr. Andrey Zinchuk
• Dr. Chen

31
Bibliography

• Rodriguez RL. Pearls in Patient Selection for
  Deep Brain Stimulation. Neurologist. 2007
  Sep13(5)253-60
• M. S. Greenberg. Surgical Treatment of
  Parkinsons Disease. Handbook of Neurosusrgery
  6th Ed., 15.2365-6, 2006
• Deuschl et al. A Randomized Trial of Deep Brain
  Stimulation for Parkinsons Disease. N Engl J Med
  2006355896-90
• Jankovic, Aguilar. Current approaches to the
  treatment of Parkinsons Disease.
  Neuropsychiatric Disease and Treatment 20084 (4)
  743-75
• Weaver et al. Bilateral Deep Brain Stimulation vs
  Best Medical Therapy for Patients With Advanced
  Parkinsons Disease A Randomized Controlled
  Trial. JAMA. 2009301(1)63-73
• Temel. Blokland.The functional role of the
  subthalamic nucleus in cognitive and limbic
  circuits. Progress in Neurobiology 76 (2005)
  393-413.
• Mercado et al. Expectation and the Placebo Effect
  in Parkinsons Disease Patients With Subthalamic
  Nucleus Deep Brain Stimulation. Movement
  Disorders. 21 (2006). 1457-1461.
• Krack et al. Five year Follow-up of Bilateral
  Stimulation of Subthalamic Nucleus in Advanced
  Parkinsons Disease.