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What you do in the early stages matter in the long run. Even a single dose of Levodopa (LD) can sensitize
the patient for motor complications (?)
Celebrities with PD Billy Graham, Pope JP II, Mohammad Ali
Parkinson plus : progressive supranuclear palsy, multiple system atrophy, cortical-basal ganglionic
degeneration, Alzheimer disease, dementia with Lewy bodies (DLB)
Brain Bank criteria for PD diagnosis
First diagnose parkinsonism, then look for all the causes, exclude PD Plus, then diagnose PD
The tremor of PD is resting mainly, 4-6/second. Postural tremor is 12-16/s. Jaw, tongue, head, feet can
be affected in PD and if they are affected add weight to the diagnosis.
Bradykinesia means decrease in rate and amplitude of movements hypomimia, decreased blinking,
drooling of saliva because of decreased swallowing.
Rigidity is enhanced by using the other limb at the same time.
Postural instability is a late feature in PD, if it is there early stages think of P Plus. Early falls is also
against the diagnosis of PD
Asymmetry is the rule in PD. If symmetrical think of PSP, VP, MSA, DIP (P plus)
Other features unfavourable for PD are: broad-based gait, early cognitive dysfunction, dyspraxia, cortical
sensory loss, early autonomic dysfunction, cerebellar signs, UMNL, supranuclear gaze palsy, stridor, poor
response to LD, rapid progress, antecollis.
There is no specific test or investigation for PD
PD typically is unilateral, insidious in onset. Jaw and leg tremor, good response to LD. LD-induced motor
complications strengthen the diagnosis of PD
Is it important to diagnose PD correctly? It is important as the progress and prognosis, as well as lifespan
differ from those of Pplus. In MSA the lifespan expected is 3-5 years. P+ is considered a death sentence.
Motor fluctuation in PD
1. Wearing off of the drug effect seen a few years after the diagnosis. It is also attributed to
adverse effect of LD. In the early stages of PD LD works well even for a full day with one dose.
But as time goes on, the effect becomes less and less, shorter and shorter. The half life of LD is
60-90 min.
2. No effect or inadequate effect
3. Unpredictable motor fluctuations on-off phenomenon (diphasic dyskinesia) on means when
the patient is at the peak effect of LD, and off means when the LD has worn off. Dyskinesia can
occur 30 min to 60 min after a dose of LD
4. Freezing of gait
Dyskinesia can be very distressing and violent. Incidence is 10% cases in one year, 80% cases would
have it in 10 years. The explanation is based on the narrowing therapeutic window of LD on the
particular patient. When the drug level crosses above the window or below the window, dyskinesia
can occur. In the early stages of the disease the window is wide. As the disease advances the
window becomes progressively narrower. Moreover, to make things worse, the window is not
constant. It can change from day to day making it very difficult to adjust dosage to make the drug
level fall within the therapeutic window. Progress of the brain pathology and the pulse therapy of
LD are blamed.
The distressing symptoms are not confined to the motor component. Non-motor symptoms are
equally disturbing to the patient.
How to prevent motor complications (and non-motor complications)?
Now the trend is to postpone use of LD as long as possible. Start selegiline (MAO-B inhibitor) 5 mg
OD/BD (known to cause insomnia). Another useful drug is amantadine (antiviral) it has modest
effect. It is good for tremor due to its anticholinergic side effects. It can be used to ward off
dyskinesia for a few months. Benzhexol artane is another anticholinergic which can be used in
relatively younger and those who can tolerate the side effects. It has predominat effect on tremor
and some effect on bradykinesia. Dopamine agonists (DA) have moderate effect: bromocriptine,
ropinirole, pramipexol, pergolide. These drugs do not cause dyskinesia. However, if the patient is
symptomatic even with these drugs do not hesitate to start LD. LD is the most effective drug in PD.
With LD, dyskinesia is more in younger compared to older patients.
Anticholinergics side effects include: urinary obstruction, confusion.
Managing motor complications: Ask the patient to chart the events, dosing time, with food or not,
etc hour to hour in detail. Study the chart and adjust the LD dosage. Ask the patients preference
dyskinesia or immobility? LD is best absorbed on empty stomach. Keep it 30-60 min pre or 60 min
post meal. Replace LD with Stalevo a combination of LD, carbidopa and entacapone or add
Comtan (entacapone). Avoid wide fluctuations of the LD level in blood. Restrict it within the
therapeutic window. Below on and above off range. Frequent smaller dosing with immediate
release formulation is advisable as its effect is more predictable. Avoid slow-release formulations.
Levetiracetam or amantadine can be added. Even liquid LD 1000 mg in 1 L water plus 1 g Vit C can
be used to adjust dose more accurately.
Apomorphine injection / infusion, intrajejunal LD infusion (Slovay), deep brain stimulation are other
methods that can be tried. For early morning dystonia use nocte slow release drug.
Pramipexole is known to cause SE like pathological gambling and hypersexuality. Trivastal visual
hallucination. VH can occur in cognitive impairment or as SE of drugs like MAO B-inhibitors,
anticholinergics, dopamine agonists and lastly LD