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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