Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.

We evaluated whether patients with early-onset Parkinson's disease (EOPD) have a different clinical profile and pharmacological response than those with late-onset disease (LOPD). We performed a retrospective analysis and an acute pharmacological challenge with L-Dopa in 34 EOPD (age at onset between 21 and 40 years) and 34 LOPD (onset after age 60) patients. All patients completed a structured questionnaire cross-checked against medical record charts and underwent an acute levodopa test. Most significant differences were in the mode of onset, time of diagnosis, and degree of initial improvement. We did not observe differences with regard to motor fluctuations. The acute levodopa test showed no differences in latency to response onset between groups. However, the magnitude of the response was greater and the duration shorter in EOPD patients. Younger patients had greater reductions in bradykinesia scores, whereas posture/gait symptomatology was less responsive in older patients. The type and severity of dyskinesias also differed significantly between groups. Our findings suggest that central pharmacokinetics, pharmacodynamics, and possibly, nondopaminergic systems play a role in the age-related differences observed in Parkinson's disease.

We assessed the effect of sleep benefit on motor performance in Parkinson's disease (PD) and analyzed its relation to pharmacologic and sleep measures. The sleep benefit phenomenon-motor improvement after sleep before drug intake-in patients with PD has been addressed by questionnaire studies, but objective data are scarce. Ten PD patients with sleep benefit were pairwisely matched to 10 PD patients without sleep benefit for gender, age, PD symptom duration, and medications. We examined motor performance at night before sleep, during morning baseline state immediately after spontaneous awakening, and continuously after intake of the usual levodopa dose. Plasma levodopa concentrations were measured serially and all-night polysomnography was performed. Between night and morning evaluations, motor state improved slightly in patients with sleep benefit and deteriorated slightly in patients without sleep benefit. The difference between both groups proved to be significant. After levodopa induced "on" state, patients with sleep benefit had more severe interdose "off" than those without. Levodopa concentrations and polysomnographic findings were similar in both conditions, although there was a trend toward more abnormal sleep measures in sleep benefit patients. Sleep benefit is a small but significant phenomenon. It does not clearly relate to a specific sleep variable; however, patients with sleep benefit showed a different response profile to levodopa. Subjective perception or possibly sensory mechanisms could play an additional role in sleep benefit in PD.

The effect of isoniazid on levodopa-induced dyskinesias has been evaluated in 20 patients with Parkinson's disease, following a serendipitous observation that choreic dyskinesias induced by levodopa in one parkinsonian patient were markedly reduced during treatment with isoniazid for tuberculous infection. A mean average isoniazid dose of 290 mg was given without any change in current antiparkinsonian treatment. "Benefit of dose" choreic dyskinesias were markedly reduced in 18 patients within the first few weeks of treatment. This effect was accompanied by an intolerable worsening of parkinsonian signs. All patients returned to their basal situation after isoniazid interferes with the therapeutic action of levodopa and dopamine agonists. The precise mechanism by which this action occurred is not known, but several possible explanations are discussed.

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