Download Parkinson`s Disease: A World of Promise

Parkinson’s Disease:
A World of Promise
Sarah Click
Dr. Julie Gurwell
Spring 2006
Background
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Movement disorder
Affects over 1 million people usually middle
aged
2nd most common ND disorder behind AD
Background cont’d
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Progression due to loss of DA neurons in
the brain
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These neurons normally project into the striatum
and eventually cause inhibition of the STN
Without them, there is hyperactivity of this portion
of the brain that controls motor fxn
Background cont’d
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Cardinal symptoms
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Bradykinesia
Resting tremor
Stiffness
Postural instability
Standard criteria to
diagnose is 2 of these
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Other symptoms
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Dyskinesias
Depression
Sleep disturbances
Psychotic symptoms
Decrease in balance
performance and gait
Hoarseness
Hypophonia (motor)
Drug Therapy– reminders
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Overall goal is to increase DA
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Dopamine agonists
Inhibit breakdown
Anticholinergics
Limited long-term efficacy of drug treatment
Undesirable side effects
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Dyskinesias
Surgeries
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Three common
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Thalamotomy
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Pallidotomy
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Deep brain stimulation
Thalamotomy and Pallidotomy
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Local anesthesia
CT, MRI, or ventriculography
Location is determined by stimulation with an
electrode
Looking for the greatest effect on symptoms with
the least amount of side effects.
Once target is identified, a lesion is made
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This is permanent
Several lesions are normally made in different parts to
maximize effects
DBS
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The area targeted is
the subthalamic
nucleus (STN) or
globus pallidus
internus (GPi)
Procedure basically
the same
Lesion not created
Electrode remains
there
Why choose DBS?
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Main goals
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Increase motor functions
Increase ADL
Decrease need for levodopa
STN DBS
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Drapier et al. studied
27 patients that
underwent bilateral
STN DBS between
1999 and 2002
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19 men and 8 women
took part in the study
Goal was to determine
quality of life before and
after surgery
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Inclusion Criteria
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Age ≤ 75
Severe PD
Drug induced
dyskinesias
Exclusion Criteria
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Cognitive impairment
Marked cerebral atrophy
on MRI
Major depression before
surgery
Results of Drapier et al.
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Significant difference in the motor functions
between pre-op off-med and post-op offmed/on-stimulation conditions with p<0.001
L-dopa dosage decreased an average of
29%
Quality of life increased by 21.1% at followup
STN DBS cont’d
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Krause et al studied 27
patients that underwent
bilateral STN DBS in 1997
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Age range from 44-72
Symptom duration 7-25 yrs
Mean follow-up time ~29.8
months (range 23-55)
Goal similar to previous
study
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Inclusion criteria
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Patients with advanced PD
Severe pharmacological
side effects
Exclusion criteria
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None listed
Krause et al. Results
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3 patients lost to follow up due to
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Intraventricular hemorrhage
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Dysphagia and death
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Corrected by a temporary external ventriculostomy in which
the lead was not replaced
Patient had dysphagia before the surgery, stimulation made
it worse, so it was turned off
Patient died of suffocation unrelated to surgery 1 ½ yrs later
No comment on last patient (not by me, by the
researchers)
Krause et al. Results cont’d
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Significant improvement in ADL, dyskinesias, and fluctuations postsurgery
Sig. imp. in freezing after 1 yr, stable for 30 months
Off-medication motor score significantly improved by 40-44% &
stable
Motor score sig. imp. On-med/on-stim (p<0.04).
Tremor suppression much better with stimulation than with
medication (p<0.05)
Stimulation improved rigidity and bradykinesia more than the
medication alone could do in this trial, results stable
SIGNIFICANT DECREASE IN LEVODOPA-EQUIVALENT DOSE
BY 39% AT 1 YR FOLLOW-UP AND 30% AT 3 YR FOLLOW-UP
(P<0.05)
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This caused a decrease in fluctuations and dyskinesias
Adverse events in Krause et al. trial
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Intraventricular hemorrhage (n=1)
Dysphagias (n=3)
Pneumonia (n=1)
Transient hyperhidrosis (n=6)
Moderate dysarthria (n=3)
Lasting hyperkinesias (n=2)
Increased falling (n=4)
Increased libido (n=1)
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Maybe an alternative to Viagra?
Note: most adverse events were related to amplitude and could
be fixed if the IPG was turned down
Three Other studies’ results
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Sig. imp. in off-med scores by 39%
42% reduction in dyskinesias
Reduction in L-dopa Equiv. dose by 24%
(p<0.017)
Adverse Events:
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Intracranial hemorrage (n=1)
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Did not have to discontinue this study once resolved
Dyskinesias (n=1)
Paresthesias (n=1)
Apraxia of lid opening (n=1)
Mood change with apathy (n=1)
Pyschosocial factors in DBS
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One study showed a suicide rate of 4.3%
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Patients observed had PD, ET, primary and secondary
dystonias, or MS-associated tremor
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All but 1 were young men with a chronic neurological cond’n
Most had episodes of severe depression before or during
the course of the disease prior to DBS, but only 2 had frank
suicidal ideations or suicide attempts
Each of these patients showed significant improvement in
their motor function following DBS surgery
No sig. changes in medications or other attributing factors to
the lifestyle of the patients before each of the suicides
Need more extensive inclusion criteria
Pyschosocial factors in DBS cont’d
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Another study shows cognitive decline in patients
post-op
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Increased risk for cognitive impairment, without any early
signs of dementia, in the elderly
Suggested there might not be enough neurologic reserve
for the DBS to work in patients past a certain point
Also observed mental slowness
Medications were reduced in this study by 46% in
the older patients and 47% in the younger,
although they cited studies that showed
medication reductions of up to 100%
Pyschosocial factors in DBS cont’d
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Cognitive improvement observed in another
study
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No signs of suicide ideation (0/76 or 0% of
patients for all you math majors!)
Psychomotor speed and working memory was
sig. imp. with stim-on
No cognitive decrease at 1 year post-op in
attention, construction, initiation,
conceptualization, or memory scores
Conclusion
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DBS is a great alternative to high L-dopa
dosages
There are some side effects that should be
considered before deciding to have the
surgery
More emphasis should be placed on
psychological function before approving the
surgery
Getting Support
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American Parkinson Disease Association
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National Parkinson Foundation
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888-400-2732
www.apdaparkinson.org
800-327-4545
www.parkinson.org
Parkinson’s Disease Foundation
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800-457-6676
www.pdf.org
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