Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation.

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

Cigarette smoking decreases cerebral blood flow suggesting increased risk for stroke.

Effects of chronic cigarette smoking on cerebral blood flow were investigated by measuring gray matter blood flow (Fg) using xenon 133 inhalation among 192 volunteers without cerebrovascular symptoms. There were 108 normal, healthy volunteers; 84 had risk factors for stroke (hypertension, hyperlipidemia, diabetes mellitus, and/or heart disease). Of both risk and nonrisk groups, 75 were habitual smokers (0.5 to 3.5 packs per day for 25 years). Comparisons of mean Fg values for both hemispheres showed significant reductions related to tobacco consumption and risk factors for stroke. Multiple-regression equations using smoking, age, risk, and alcohol consumption indicated a combined R2 value of 0.22. Smoking seems to be a potent risk factor decreasing cerebral blood flow probably by enhancing cerebral arteriosclerosis. Chronic cigarette smoking in persons with other risk factors further reduced Fg values in an additive manner when compared with subjects who had corresponding risk factors who did not smoke.