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Background: In pre-clinical studies of Alzheimer’s disease (AD) transgenic mice, bryostatin restored synaptic connections, prevented neuronal death, reduced amyloid plaques, and reduced neurofibrillary tangles. Objective: Within pre-specified cohorts of advanced AD patients in two double-blind placebo-controlled bryostatin Phase II trials, to conduct exploratory statistical analyses of patients with identical conditions of enrollment and treatment. Methods: Severe Impairment Battery (SIB) scores above baseline at 5, 9, and 13 weeks were analyzed initially in the complete cases, with multiple imputation methods based on an iterative Markov chain Monte Carlo algorithm used for missing SIB scores. To mitigate confounding by a chance imbalance of 4.9 SIB baseline scores (Study #203), each patient was used as their own control with differences in 13-week SIB from baseline in single trial and pooled analyses to measure benefit at 13 weeks using general estimating equations (GEE) modeling. Results: Patients treated with bryostatin pre-specified at Mini-Mental State Examination scores 10–14, without memantine, showed baseline balance, complete safety, and SIB improvements at 13 weeks with multiple imputation analysis: Study #203 = 4.1 SIB points above baseline (p = 0.005), and Study #202 = 4.2 SIB points above baseline (p = 0.016). An increased power (N = 95) “pooled analysis” showed an increased SIB over time and a higher mean SIB at 13 weeks in the bryostatin treatment group (p

Background: Bryostatin-activated PKC epsilon pre-clinically induces synaptogenesis, anti-apoptosis, anti-amyloid-β oligomers, and anti-hyperphosphorylated tau. Objectives: To investigate bryostatin safety, tolerability, and efficacy to improve cognition in advanced Alzheimer’s disease (AD) patients. Methods: A double-blind, randomized, placebo-controlled Phase II, 12-week trial of i.v. bryostatin for 150 advanced AD patients (55–85) with MMSE-2 of 4–15, randomized 1:1:1 into 20 μg and 40 μg bryostatin, and placebo arms. The Full Analysis Set (FAS) and the Completer Analysis Set (CAS) were pre-specified alternative assessments (1-sided, p

Cocaine use in the United States has reached epidemic proportions, and increased availability of "crack" since 1983 has noticeably increased the incidence of neurovascular complications. In this report, we examine the relationship between cocaine use and ischemic infarct. This study reports 18 cases of ischemic cerebrovascular events, which occurred among 15 men and three women aged 21-47 years who were evaluated in a 2-year period. Clinical presentations include thirteen cases with hemispheric infarcts, two brain stem strokes, two anterior spinal artery infarcts, and one with both hemispheric and cerebellar infarcts. Nine patients smoked crack, four snorted cocaine, and three injected it intravenously. In two cases, the route of administration could not be determined. Two patients died, but the other survived with various degrees of neurological deficit. Traditional risk factors for strokes were identified in only six patients, suggesting that these factors are not necessary for the occurrence of a cocaine-related infarct. Multiple overlapping mechanisms may be responsible, including vasospasm, sudden onset of hypertension, myocardial infarction with cardiac arrhythmias, increased platelet aggregation, and vasculitis.

Background: Olfactory function in multiple sclerosis (MS) has not been extensively studied. Anecdotal cases describing disturbances in olfaction in MS have been reported; however, different investigations have yielded conflicting results. We per formed a controlled study using a standardized quantitative test of olfactory function to determine the occurrence of microsmia in MS.Methods: The University of Pennsylvania Smell Identification Test (UPSIT) was administered to sixteen patients with clinically definite MS and fourteen age- and sex- matched controls. Additionally, each patient and control was given a detailed ques tionnaire to ascertain subjective estimates of olfactory function. Patients and con trols with concurrent conditions associated with microsmia or anosmia were excluded from the study.Results: In the patient group, mean expanded disability status scale (EDSS) was 5.2 (range 1.0 to 8.5) and mean disease duration was 12.3 years (3 to 50). One patient had subjective microsmia. Mean UPSIT scor...