CALM-PD (Comparison of the agonist pramipexole with levodopa on motor complications of Parkinson's disease) is a randomized, multicenter, double-blind, controlled clinical trial designed to compare the policy of initial treatment of pramipex ole with the policy of initial treatment with levodopa in early, symptomatic Parkinson's disease with regard to the development of dopamineragic motor complications. At 22 American and Canadian sites, 301 eligible subjects requiring antiparkinsonian therapy to treat emerging disability were enrolled in CALM-PD and randomized to (i) active pramipexole and placebo levodopa or (ii) placebo pramipexole and active levodopa. Subjects are being evaluated systematically at regular intervals during a 23.5-month period to determine if and when dopaminergic motor complications (wearing off, dyskinesias, "on-off " effects) occur. In addition, quality-of-life outcomes, economic outcomes, and functional imaging outcomes are being assessed in standard fashion with [I-123]beta-CIT and SPECT imaging throughout the trial. The study design contains many provisions to approximate routine clinical practice and to produce data about clinical effectiveness, tolerability, and cost to facilitate the evidence-based practice of neurology.

Article abstract-Over the past 15 years we have treated 526 patients with severe hyperkinetic movement disorders with tetrabenazine (TBZ), a monoamine-depleting and a dopamine-receptor-blocking drug. We report here the results in 400 patients with adequate follow-up. The response was rated on a scale of 1 to 5 (1 = marked improvement, 4 = no response, 5 = worsening) and was assessed initially and at the last clinic visit. The average duration of TBZ treatment was 28.9 months (+/- 31.1; range, 0.25 to 180 months). The global response rating of 1 (marked improvement) was recorded in 89.2% of 93 patients with tardive stereotypy, 83.3% of 12 with myoclonus, 82.8% of 29 with Huntington's disease, 80.5% of 82 with tardive dystonia, 79.3% of 29 with other movement disorders, 62.9% of 108 with idiopathic dystonia, and in 57.4% of 47 with Tourette's syndrome. The most common side effects included drowsiness (36.5%), parkinsonism (28.5%), depression (15.0%), insomnia (11.0%), nervousness or anxiety (10.3%), and akathisia (9.5%). The side effects were controlled with reduction in the dosage. TBZ is an effective and safe drug for the treatment of a variety of hyperkinetic movement disorders. In contrast to typical neuroleptics, TBZ has not been demonstrated to cause tardive dyskinesia. NEUROLOGY 1997;48: 358-362

Motor fluctuations associated with levodopa therapy are common problems encountered in the long-term treatment of Parkinson's disease (PD). Entacapone, a peripherally acting, reversible inhibitor of catechol-O-methyltransferase, slows the elimination of levodopa in humans by reducing the formation of 3-O-methyldopa. We conducted a placebo-controlled, double-blind, parallel-group, multicenter trial of entacapone in PD patients with motor fluctuations. Two hundred five patients were randomized to receive either entacapone 200 mg or matching placebo with each dose of levodopa and were followed for 24 weeks. The primary measure of efficacy was the change in percentage of ''on'' time (relief of parkinsonism) while awake, as recorded by subjects at home in diaries completed at 30-minute intervals. At baseline, patients averaged approximately 10 hours of ''on'' time per day while awake (60.5% ''on'' time), and entacapone treatment increased the percent ''on'' time by 5.0 percentage points. The effect of entacapone was more prominent in patients with a smaller percent ''on'' time (<55%) at baseline, and increased as the day wore on. Entacapone is effective at increasing the duration of response to levodopa and at relieving parkinsonism in patients experiencing motor fluctuations and was well tolerated during the 24 weeks of treatment.

To study the relation between essential tremor (ET) and Parkinson's disease (PD), we compared the frequency of familial tremor in relatives of patients with PD (N = 391), ET (N = 140), and the combination of ET and PD (N = 125) with the frequency in patients with progressive supranuclear palsy (PSP) (N = 99) and normal age-matched controls (N = 104). Tremor was present in 96 (5.1%) of 1,874 parents and siblings of patients with PD, 152 of 650 (23.4%) relatives of patients with ET, 91 (20.7%) of 439 relatives of patients with ET-PD, 12 of 462 (2.6%) relatives of patients with PSP, and 10 of 448 (2.2%) relatives of normal controls. The high frequency of familial tremor among relatives of patients with PD, and especially those with the ET-PD combination, compared with relatives of patients with PSP or of normal controls suggests that there is an association of PD and familial tremor. Since the most common form of familial tremor is ET, our study provides support for the notion that ET and PD are pathogenetically related. We also found that parents with tremor lived on the average 9.2 years longer than those without tremor. The association of familial tremor with significantly increased longevity suggests that familial tremor confers some anti-aging influence. Alternatively, tremor may be a simple byproduct of the aging process.