Andreas Neophytides

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.

Central amine metabolism in Alzheimer's disease: in vivo relationship to cognitive deficit.

Levels of the amine metabolites homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) were measured in the cerebrospinal (CSF) fluid of drug-free patients with Alzheimers disease and compared to levels in a group of controls. No significant differences were found in CSF HVA and MHPG, although the Alzheimers group was severely demented. Platelet monoamine oxidase (MAO) enzyme kinetics were measured and did not differ between controls and Alzheimer patients. The degree of dementia did not show any significant correlation with the levels of HVA or MHPG. It was concluded that, unlike previous reports in the literature, the dementia of Alzheimers disease was not related to changes in central catecholamine metabolism nor was it associated with increased platelet MAO activity.

Treatment of advanced Parkinson disease with pergolide.

Pergolide mesylate, a semisynthetic ergoline and a potent, long-acting central dopamine agonist, was tested in 13 patients with advanced Parkinson disease and diurnal oscillations in performance (“wearing-off” or “on-off” phenomena or both) whose response to levodopa had diminished considerably. Among all nine patients who completed the initial clinical trial, pergolide alone (two patients) or combined with levodopa (seven patients) had a marked antiparkinsonian effect. There was a significant reduction (p < 0.05) in rigidity, bradykinesia, gait disorder, and total Parkinson disease disability score. Pergolide had a marked effect in all the patients with “wearing-off” or “on-off” phenomena or both, resulting in a significant increase (p <0.01) in the duration of the time patients were “on.” The number of hours in which patients were “on” increased from 3.8 ± 0.5 (SEM) to 11.4 ± 0.8 (SEM). The mean daily dose of pergolide was 2.4 mg (range, 2 to 5 mg). Ten months later, all nine patients are doing well. Pergolide is an effective drug in patients with advanced Parkinson disease and reduces “on-off” phenomena.

Long-term efficacy of bromocriptine in Parkinson disease.

Twenty-eight patients with Parkinson disease (PD) were treated with bromocriptine for at least 2 years (mean, 2.8 years; range, 2 to 5 years). All of them had first been treated with levodopa (alone or combined with carbidopa, as Sinemet) for 7.4 years (range, 1 to 10 years). At the time bromocriptine was started, all were showing increasing disability. In these patients, attempts to increase levodopa resulted in adverse effects, and attempts to decrease levodopa resulted in increased parkinsonism. Bromocriptine (mean daily dose, 56 mg) was added to levodopa and resulted in improvement of at least one stage (Hoehn and Yahr scale) in 21 of the patients. After 2 years, five of these patients continue to maintain this improvement. The remaining patients, although there has been deterioration, maintain some of their original improvement. Bromocriptine, when added to levodopa, results in improvement that is maintained, in part, for at least 2 years. The ratio of bromocriptine to levodopa has to be periodically readjusted.

Brain metastases from ovarian cancer

Brain metastasis from ovarian carcinoma is a relatively rare phenomenon. At NYU Medical Center five patients were treated for this entity from 1982 to 1985. The stage at presentation ranged from stage I to stage III, and all patients had received or were receiving chemotherapy. Two patients had active disease elsewhere at diagnosis of brain metastasis, but three patients were otherwise NED. Three patients had solitary cerebellar disease, and two patients had multiple lesions. All patients were treated with whole brain radiotherapy to 3 000 cGy, with neurological improvement in three of the five patients.The central nervous system may need special consideration for prophylactic treatment in those patients with ovarian cancer who receive adjuvant chemotherapy.

Further studies with pergolide in Parkinson disease

Pergolide was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily reponding to levodopa. The group included 45 patients with on-off phenomena. Pergolide, when combined with levodopa, resulted in a 44% decrease in disability as assessed in the on period, a 15% decrease in disability as assessed in the off period, and a 148% increase in the number of hours in which patients were on (from 4.6 ± 0.3 hours to 11.4 ± 0.6 hours). All these changes were significant at 1%. Forty-one of the 56 patients (59%) improved when pergolide was added to levodopa. Mean dose of pergolide was 2.5 mg (range, 0.2 to 10.0 mg). Mean duration of the study was 13 months (range, 1 day to 34 months). Maximum improvement occurred within 2 months and began to decline, usually after 6 months. The major adverse effects necessitating discontinuing pergolide were the occurrence of an organic confusional syndrome (six patients), increased dyskinesias (four patients), and cardiovascular abnormalities (three patients). Nine patients discontinued pergolide because of a lack of effect or declining effect.

Lisuride in Parkinson disease Efficacy of lisuride compared to levodopa

Lisuride hydrogen maleate, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was tested in 10 patients with moderate to marked Parkinson disease whose response to levodopa had diminished. In the group of 10 patients, there was a significant reduction (p =z 0.05) in bradykinesia, gait disorder, and total Parkinson disease disability score when levodopa was replaced with lisuride. The mean dose of lisuride was 3.6 mg per day. Among the 10 patients, 5 were better on lisuride than on levodopa, and 4 continue on lisuride 1 year later. A decline in efficacy was noted in all four after a mean of 45 months. Adverse effects necessitating discontinuing the drug were mental changes in three patients and nausea in one patient. Lisuride, when used alone, has definite antiparkinsonian activity and is a promising new drug.

Cardiac effects of pergolide

We examined the effect of pergolide, a semi synthetic ergot alkaloid, alone or combined with carbidopa and levodopa (Sinemet), on the cardiac rhythm of 12 patients with Parkinsons disease. The patients were selected on the basis of severe Parkinsons disease and stable cardiac rhythm as determined by I to 5 days of Hoher monitoring. Monitoring was then carried out for an additional period of between 2 and 10 wk while the patients were on pergolide. Seven of the 12 patients had repetitive ventricular rhythms (RVRs). These were isolated, infrequent, and not associated with increases in premature ventricular contractions. The dose at which the RVRs occurred may be a function of the presence or absence of heart disease, but the significance of RVRs remains to be determined.

Long‐term treatment with pergolide Decreased efficacy with time

We studied the effect of pergolide (combined with levodopa) in 17 patients with Parkinsons disease, including 15 with “wearing off” or on-off phenomena, who had been taking pergolide for at least 2 years. Mean duration of the study was 27.8 months. All 17 patients improved initially, but the improvement later faded. Mean disability score, which decreased initially by 60% (significant), was decreased only by 20% after 2 years (not significant). Wearing off and on-off phenomena, which improved initially, became prominent again. Four patients lost all the improvement, nine patients lost much of the improvement, and four maintained much of the improvement. Mean dose of pergolide was 2.2 mg (range, 0.8 to 5.0 mg).

Lisuride combined with levodopa in advanced Parkinson disease

lisuride, a semisynthetic ergoline and potent central dopamine and serotinin agonist, was combined with levodopa in 20 patients with advanced Parkinson disease who were no longer responding satisfactorily to levodopa, including 14 patients with “on-off” phenomena. Every patient who completed the week trial improved significantly (p <0.01), with a decrease in all symptoms. The mean dose of lisuride was 2.4 mg per day. The dose of levodopa (mg of levodopa in Sinemet) was reduced from 1030 to 920 mg. Among the patients with “on-off” phenomena, there was a significant increase in the time in which they were “on” (mobile) from 4.6 to 9.6 hours. In 5 of 10 patients who have been on lisuride for at least 1 year, there has been no decline in efficacy.