Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson's disease. A multicenter 5-year study. The CR First Study Group.

BACKGROUND: Motor response fluctuations and dyskinesias compromise long-term levodopa therapy in Parkinson's disease. Variations in plasma levodopa levels contribute to adverse reactions associated with chronic therapy. Therefore, sustained-release levodopa preparations may be associated with less motor fluctuations and a better outcome. We conducted a large, 5-year, multicenter study to address this hypothesis. METHODS: Six hundred and eighteen nonfluctuating patients with Parkinson's disease never exposed to levodopa therapy were randomized to (Sinemet CR 50/200) sustained-release or immediate-release (Sinemet 25/100) carbidopa/levodopa preparations in 35 centers worldwide. Dosage titration occurred over the 5 years of evaluations to maintain an optimal response. The primary endpoint, the 'event', was the presence of motor fluctuations, as defined by 20% 'off' time or 10% 'on' time with dyskinesias as recorded in the patient diary, or greater than or equal to a 50% positive response on the physician fluctuations questionnaire. Clinical rating scales, Nottingham Health Profile (NHP) and adverse reactions were also recorded. FINDINGS: During the 5 years of the study, both treatment groups responded extremely well to therapy. The incidence of all patients reaching the 'event' was low, approximately 20% by diary criteria and 16% by questionnaire definition, and there was no significant difference between the two treatment groups. Activities of daily living scores in the Unified Parkinson Disease Rating Scale (UPDRS) consistently favored the Sinemet CR treatment group and a number of the NHP scales also favored the CR group. Based upon the frequency of adverse experiences, and the overall low incidence of withdrawals, the two treatment groups demonstrated very similar safety profiles. The most common drug-related effect was nausea; seen in 20% of patients. Other drug-related effects were dizziness, insomnia, abdominal pain, dyskinesia, headache and depression. Drug-related withdrawals were less than 10% of all patients, primarily due to nervous/psychiatric complaints. INTERPRETATION: During a 5-year treatment period, control of parkinsonian symptoms was maintained by both immediate-release and sustained-release carbidopa/levodopa. Both treatment regimens were associated with a low incidence of motor fluctuations and dyskinesias. There was a statistically significant difference (p < 0.05) in activities of daily living as measured by the UPDRS in favor of Sinemet CR.

Factor structure and reliability of the Alzheimer's Disease Assessment Scale in a multicenter trial with linopirdine.

The Alzheimer's Disease Assessment Scale (ADAS) has assumed a primary role in assessment of treatment responses in large-scale multicenter trials of drugs being evaluated for treatment of dementia in elderly patients. Data from 280 patients with Alzheimer's disease were analyzed to evaluate factor structure and reliability. Results confirm the presence of three primary factors interpreted as mental status, verbal fluency, and praxis. The presence of a large general factor underlying those more specific dimensions also supports the utility of the composite ADAS cognitive score that has been used as a primary outcome measure in previous drug trials. Test-retest reliability of the factor scores were calculated to be 0.83, 0.78, and 0.87. Test-retest reliability of the composite ADAS cognitive score was 0.90. Statistics useful for estimation of sample sizes for future multicenter trials are provided.

Factor structure and scoring of the SKT test battery.

The SKT (Syndrom Kurztest) has been used in the assessment of treatment responses in numerous clinical trials for treatment of dementia in German-speaking Europe. Data from 265 patients with mild to moderate Alzheimer's disease in a study conducted in the U.S. were analyzed to evaluate factor structure, common and specific subtest content, reliability, and concurrent validity. Results confirm the presence of two primary factors of memory and attention. Test-retest reliability of the factor scores was estimated to be .75 and .93. Test-retest reliability of the composite SKT total score was .90. The correlations between the SKT memory and attention factor scores and the MMSE and ADAS measurements of dementia also support validity with regard to the broader construct of cognitive dysfunction.

Early management of aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study.

The overall results are presented of early medical management and delayed operation among 249 patients studied during the period 1974 to 1977, treated within 3 days of subarachnoid hemorrhage (SAH) and evaluated 90 days after aneurysm rupture. The results included 36.2% mortality, 17.9% survival with serious neurological sequelae, and 46% with a favorable outcome. Of the patients admitted in good neurological condition, 28.7% had died and only 55.7% had a favorable recovery at 90 days after SAH. These figures represent the results despite effective reduction in early rebleeding by antifibrinolytic therapy and successful surgery in those patients reaching operation. Further therapeutic advances are needed for patients hospitalized within a few days after SAH.

Antifibrinolytic therapy in patients with aneurysmal subarachnoid hemorrhage. A report of the cooperative aneurysm study.

Antifibrinolytic therapy was used in 1,114 patients who had aneurysmal subarachnoid hemorrhage (SAH) and who were treated by the 13 institutions of the Cooperative Aneurysm Study. Patients were started on treatment within one week after SAH was diagnosed, and therapy was discontinued 14 days after the ictus. Rebleeding occurred in 10% of the treated patients. Overall mortality among the treated patients during the two weeks following hemorrhage was 10.7%. Though some minor and a few major side effects occurred, serious complications of therapy were infrequent.

Intracranial aneurysms and subarachnoid hemorrhage - report on a randomized treatment study. IV-A. regulated bed rest.

Three weeks of regulated bed rest was one of four treatments evaluated in the Cooperative Aneurysm Study. A total of 187 patients with a recently ruptured intracranial aneurysm had subarachnoid hemorrhage confirmed by lumbar puncture. A group of 124 patients were assigned to treatment within 7 days after the bleed, 49 between 8 and 21 days, and 14 between 22 days and 92 days. During the mean follow-up interval of 6.5 years, mortality was 55.1%. A proved rebleed was the cause of death in 34.2%, progressive deterioration from aneurysm rupture in 8.0%, and a suspected rebleed in 4.8%. A total of 47.1% died of causes related directly to the cerebral effects of the ruptured aneurysm.

Alexia with left homonymous hemianopia without agraphia. A case report with autopsy findings.

Unusual findings at autopsy prompted this case report of a patient with the syndrome of alexia without agraphia. The expected disconnection of the left angular gyrus from both visual cortices was not found at postmortem examination. Multiple cerebral metastases were identified, but none were present in the presumed pathways connecting the left occipital lobe and the left angular gyrus.

Intracranial aneurysms and subarachnoid hemorrhage. A cooperative study. Antifibrinolytic therapy in recent onset subarachnoid hemorrhage.

In this cooperative study among 13 institutions, 502 patients were treated with antifibrinolytic medication (epsilon-aminocaproic acid or tranexamic acid) within a 14-day period following rupture of an intracranial aneurysm. Mortality at the end of 14 days was 11.6%; proved rebleed rate was 12.7%. Patients with an internal carotid or anterior cerebral aneurysm had the highest mortality and rebleed rate. Most rebleeds occurred between the sixth and eleventh days following the initial bleed. Significantly higher mortality was reported among patients with cerebral vasospasm, yet rebleed rate was no different among those patients with or without vasospasm. The same pattern was observed among patients with a mean blood pressure value above and below 110 mm Hg. We conclude that antifibrinolytic therapy provides beneficial treatment to patients with recent onset subarachnoid hemorrhage (SAH) following rupture of an intracranial aneurysm.