Deprenyl in the treatment of symptom fluctuations in advanced Parkinson's disease.

Deprenyl, a selective inhibitor of monoamine oxidase, type B, which is free of the "tyramine effect," may ameliorate symptom fluctuations in advanced Parkinson's disease (PD). We randomized 96 patients with marked symptom fluctuations at three centers to receive either deprenyl 5 mg b.i.d. or placebo in parallel fashion in addition to a previously optimized levodopa/carbidopa (Sinemet) regimen. Disability was recorded hourly at home by patients 3 days weekly during the 2-week baseline and the 6-week treatment period. Disability during the "on" state was assessed each week by examination. Mean hourly self-assessment of gait improved in 28 of 50 patients (56%) receiving deprenyl (mean degree of improvement 0.25 points on a 0-2 scale) and in 14 of 46 (30.4%) taking placebo (mean 0.15). Mean hourly overall symptom control improved in 29 (58%) taking deprenyl (mean 0.34) and in 12 (26.1%) taking placebo (mean 0.15) (p less than 0.01 for each parameter). No significant improvement occurred in the objective quality of the "on" state with deprenyl. Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group. Adverse effects included nausea, light-headedness, dyskinesias, and hallucinations, all of which abated after the Sinemet dose was reduced. We conclude that deprenyl is of moderate benefit in a majority of patients with symptom fluctuations complicating PD and is generally well tolerated.

Familial aspects of CT scan abnormalities in chronic schizophrenic patients.

To investigate the possibility that lateral cerebral ventricular size may be under genetic control, we compared the computed tomography (CT) scans of 17 healthy siblings from 7 normal sibships. The CT scans of 10 chronic schizophrenic patients and 12 of their nonschizophrenic siblings were also compared. A trend was found for a correlation of ventricular size between siblings in the healthy sibships (ICC = 0.25, p = 0.1) but not in the schizophrenic sibships (ICC = -0.05). In each sibship the schizophrenic patient had the largest ventricles; in seven cases they exceeded the normal range. Although the discordant siblings were all well within the normal range, their ventricles were larger (p = 0.001) than those of the controls. The findings suggest a genetic component to ventricular size in healthy individuals and that CT findings in schizophrenics are not coincidental familial traits but markers of the illness. The implications of the findings in the discordant siblings are discussed.

Sodium valproate in the treatment of cerebellar disorders.

Because of the high concentrations of gamma-aminobutyric acid (GABA) in the cerebellar cortex and nuclei, an attempt was made to enhance GABAergic transmission in patients with cerebellar disease. Maximum tolerated doses of sodium valproate, a drug which inhibits the degradation of GABA, failed to influence cerebellar deficits in a double blind crossover study on six patients.

Structural abnormalities in the cerebral cortex of chronic schizophrenic patients.

Enlarged cerebral ventricles in chronic schizophrenic patients suggest a process of mild cerebral atrophy occurs in some. To see if this process involves the cerebral cortex, the widths of the Sylvian fissure, the interhemispheric fissure, and three cortical sulci were measured blindly on computerized tomography (CT) scans of 75 chronic psychiatric patients and 62 asymptomatic volunteers, all less than 50 years of age. A total of 19 of the 60 patients with chronic schizophrenia had at least one abnormality. All 15 patients with other diagnoses were within the control range. Comparing those chronic schizophrenic patients with abnormalities to those without them, there were no significant differences in age, length of illness or treatment, and length of hospitalization. From this and ventricular size data, two thirds of the chronic schizophrenics had some cerebral structural abnormality. Ventricular enlargement did not correlate significantly with cortical abnormalities. Therefore, more than one etiology may account for the structural abnormalities found in chronic schizophrenic patients.

Lateral cerebral ventricular enlargement in chronic schizophrenia.

To investigate if cerebral ventricular enlargement is associated with chronic schizophrenia, computerized tomography scans from 73 psychiatric patients were compared with 56 asymptomatic volunteers all less than 50 years old. Ventricular size was significantly greater in the subgroup of 58 chronic schizophrenic patients than in the controls. Of the chronic schizophrenic patients, 40% were outside the control range; 53% exceeded 2 SDs of the control mean. Neither duration of illness nor length of hospitalization correlated with ventricular size. The 44 chronic schizophrenic patients who had never been treated with electroshock therapy (EST) had larger ventricles than controls. A group of seven nonchronic schizophrenic patients also had enlarged ventricles; the eight patients who were either schizoaffective or nonschizophrenic did not differ from controls. This study shows that lateral cerebral ventricular enlargement is associated with chronic schizophrenia; it suggests that this is not a result of treatment.

Thrombocytopenia associated with sodium valproate treatment.

The administration of sodium valproate to 30 patients in daily doses of 1,200 to 3,000 mg was associated with a significant reduction of the platelet count. Thrombocytopenia without any concomitant bleeding abnormalities occurred in 10 of the patients. Platelet counts returned to baseline levels after withdrawal of the drug.