A total of 335 patients with early Parkinson's disease (PD) were enrolled in a multicenter, randomized, double-blind trial designed to assess the efficacy and safety of pramipexole. Entry was restricted to patients with idiopathic PD who were not receiving levodopa. Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication. This was followed by a 24-week period of maintenance therapy. The mean daily dose during the maintenance period was 3.8 mg. Pramipexole significantly reduced the severity of PD symptoms and signs compared with placebo, as measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale at week 24 compared with baseline (p < or = 0.0001). Differences between the active drug and placebo groups emerged at week 3 (1.5 mg/d) in the ascending-dose interval and persisted throughout the maintenance phase (p < or = 0.0001). The majority of patients completed the study (pramipexole 83%, placebo 80%). In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients. No clinically significant changes were noted in blood pressure or pulse rate. Overall, these results indicate that pramipexole is safe and effective in the treatment of early PD.

Patients with Parkinson's disease may have more difficulty performing repetitive motor acts than single motor acts because of bradykinesia and skeletal muscle rigidity. We thought that repetitive ventilatory tasks might be similarly limited and that this dysfunction would likely contribute to respiratory muscle fatigue. We studied 9 patients with Parkinson's disease who had no evidence of restrictive or obstructive lung disease and 5 normal age-matched control subjects who performed repetitive, forced inspiratory resistive-loaded tasks. The time a given mean airway opening pressure could be sustained, the incremental oxygen cost of breathing, and the work rate of breathing (W) were measured. Although maximal static inspiratory pressures were comparable in both groups, 8 of the 9 patients could not sustain as high a W in the resistive-loaded tasks as could the normal control subjects (41.0 +/- 23.0 versus 67.7 +/- 29.1 J/min; mean +/- SD, p less than 0.01) and the efficiency of breathing was reduced (2.0 +/- 0.8 versus 3.8 +/- 1.4%; p less than 0.01). These findings are similar to derangements of task performance by peripheral skeletal muscle groups in Parkinson's disease.

Smooth pursuit eye movement (SPEM) dysfunction is a putative genetic marker for schizophrenia, but it has also been described in major depression. The authors longitudinally evaluated effects of clinical state on SPEM quality in patients with depression. Prior to ECT, SPEM abnormality characterized 42% of 24 severely depressed patients, 60% of 30 schizophrenia patients, and 5% of 20 control subjects. SPEM was significantly correlated to Hamilton Rating Scale for Depression scores (r = 0.49, P = 0.02) in the depressed patients. Although SPEM was transiently disrupted by an acute ECT treatment, it improved during the treatment course. This improvement of SPEM quality with clinical recovery suggests that SPEM abnormality may be a state marker in severe major depression, in contrast to its invariable trait nature in schizophrenia.

Odor discrimination deficits were found in 80% of 20 schizophrenia patients and in none of the 20 age- and sex-matched comparison subjects. Olfactory discrimination was reliably measured in the patients. Twelve patients in this study also had smooth pursuit eye movement (SPEM) qualitatively recorded. The olfactory discrimination scores were highly correlated to SPEM but not to other clinical measures. This correlation suggests a shared neurobiology, possibly involving working memory.