Parkinson’s Disease: A World of Promise
Sarah Click
Dr. Julie Gurwell
Spring 2006
Background Movement disorder Affects over 1 million people usually middle
aged 2nd most common ND disorder behind AD
Background cont’d Progression due to loss of DA neurons in
the brain 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 Cardinal symptoms
Bradykinesia Resting tremor Stiffness Postural instability
Standard criteria to diagnose is 2 of these
Other symptoms Dyskinesias Depression Sleep disturbances Psychotic symptoms Decrease in balance
performance and gait Hoarseness Hypophonia (motor)
Drug Therapy– reminders Overall goal is to increase DA
Dopamine agonists Inhibit breakdown Anticholinergics
Limited long-term efficacy of drug treatment Undesirable side effects
Dyskinesias
Surgeries Three common
Thalamotomy
Pallidotomy
Deep brain stimulation
Thalamotomy and Pallidotomy 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
This is permanent Several lesions are normally made in different parts to
maximize effects
DBS 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? Main goals
Increase motor functions Increase ADL Decrease need for levodopa
STN DBS Drapier et al. studied
27 patients that underwent bilateral STN DBS between 1999 and 2002 19 men and 8 women
took part in the study Goal was to determine
quality of life before and after surgery
Inclusion Criteria Age ≤ 75 Severe PD Drug induced
dyskinesias Exclusion Criteria
Cognitive impairment Marked cerebral atrophy
on MRI Major depression before
surgery
Results of Drapier et al. Significant difference in the motor functions
between pre-op off-med and post-op off-med/on-stimulation conditions with p<0.001
L-dopa dosage decreased an average of 29%
Quality of life increased by 21.1% at follow-up
STN DBS cont’d Krause et al studied 27
patients that underwent bilateral STN DBS in 1997 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
Inclusion criteria Patients with advanced PD Severe pharmacological
side effects
Exclusion criteria None listed
Krause et al. Results 3 patients lost to follow up due to
Intraventricular hemorrhage Corrected by a temporary external ventriculostomy in which
the lead was not replaced Dysphagia and death
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 Significant improvement in ADL, dyskinesias, and fluctuations post-
surgery 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)
This caused a decrease in fluctuations and dyskinesias
Adverse events in Krause et al. trial 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)
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 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:
Intracranial hemorrage (n=1) 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 One study showed a suicide rate of 4.3%
Patients observed had PD, ET, primary and secondary dystonias, or MS-associated tremor
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 Another study shows cognitive decline in patients
post-op 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 Cognitive improvement observed in another
study 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 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 American Parkinson Disease Association
888-400-2732 www.apdaparkinson.org
National Parkinson Foundation 800-327-4545 www.parkinson.org
Parkinson’s Disease Foundation 800-457-6676 www.pdf.org
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