ABSTRACT
Elevated plasma levels of homocyst(e)ine [H(e)] are surprisingly common and strongly associated with endothelial dysfunction and a marked increase in vascular risk. Treatment with a combination of folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12) reduces plasma H(e) levels in most cases, restores endothelial function, and regresses carotid plaque, but there is no evidence that such treatment will reduce clinical events. The Vitamin Intervention for Stroke Prevention (VISP) study is a double-masked, randomized, multicenter clinical trial designed to determine if, in addition to best medical/surgical management, high-dose folic acid, vitamin B6, and vitamin B12 supplements will reduce recurrent stroke compared to lower doses of these vitamins. Patients at least 35 years old with a nondisabling ischemic stroke within 120 days, and screening plasma H(e) > the 25th percentile of benchmark population data are eligible. Secondary endpoints are myocardial infarction or fatal coronary heart disease. This paper describes the design and rationale of the study.
Subject(s)
Cerebral Infarction/prevention & control , Folic Acid/administration & dosage , Pyridoxine/administration & dosage , Vitamin B 12/administration & dosage , Adult , Aged , Cerebral Infarction/blood , Cerebral Infarction/etiology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Folic Acid/adverse effects , Homocysteine/blood , Homocystine/blood , Humans , Male , Middle Aged , Pyridoxine/adverse effects , Risk Factors , Vitamin B 12/adverse effectsABSTRACT
Cerebral hypoxia is a major component of immediate and secondary cell damage caused by ischemia. Hyperbaric oxygen (HBO) is a potent means to increase the amount of oxygen dissolved in blood plasma. The effectiveness of HBO in clinical and experimental cerebral ischemia, however, is controversial. We sought to determine whether treatment with HBO initiated early after focal cerebral ischemia-onset protects the brain when experimental conditions such as brain temperature are controlled. Male Wistar rats (n=57) underwent reversible filament occlusion of the right middle cerebral artery (MCA) for 75 min. Animals were awakened after filament introduction and assessed for presence of forelimb paresis. Rats then underwent a 60-min course of either 100% O(2) at 1.0 atmosphere absolute (ata; control group), HBO 1.5 ata, or HBO 2.5 ata in a customized HBO chamber allowing physiological monitoring and pericranial temperature control. The filament was then removed. Seven days after ischemia, rat behavior was scored from 3-18 (18=normal) and brains were removed for histological analysis of infarct volume. Rats treated with HBO 2.5 ata had better mean+/-standard deviation (S.D.) behavioral scores (14+/-2; p<0.05) than control (10+/-3) or HBO 1.5-ata-treated animals (11+/-3). Similarly, total infarct volumes (mean+/-S.D.) were smaller in animals receiving HBO at 2.5 ata (76+/-65 mm(3); p<0.05) compared to control (129+/-83 mm(3)) and HBO 1.5-ata (119+/-68 mm(3))-treated groups. Cortical infarction occurred less frequently in HBO 2. 5-ata-treated than in control animals (44% vs. 71%; p<0.05). We conclude that HBO can improve outcome after temporary focal ischemia when treatment is started early after ischemia-onset but HBO dose appears important. Potential mechanisms include enhanced oxygen supply to marginally perfused cells.
Subject(s)
Behavioral Symptoms/physiopathology , Hyperbaric Oxygenation , Ischemic Attack, Transient/therapy , Animals , Behavior, Animal/drug effects , Blood Gas Analysis , Cerebral Cortex/drug effects , Cerebral Cortex/pathology , Dose-Response Relationship, Drug , Infarction, Middle Cerebral Artery/physiopathology , Ischemic Attack, Transient/physiopathology , Male , Oxygen/administration & dosage , Rats , Rats, WistarABSTRACT
Management of patients with sudden neurological deficit must be based on complete knowledge of the underlying cause. In about 80% of such patients, a careful history and examination will lead to a precise etiologic and anatomic diagnosis. If the deficit is vascular in etiology, therapy and prognosis depend on its stage of evolution.
Subject(s)
Cerebral Infarction/therapy , Anticoagulants/therapeutic use , Anticonvulsants/therapeutic use , Barbiturates/therapeutic use , Brain Edema/drug therapy , Cerebral Infarction/diagnosis , Cerebral Infarction/drug therapy , Cerebrovascular Disorders/rehabilitation , Endarterectomy , Humans , Hyperbaric Oxygenation , Platelet Aggregation , Temporal Arteries/surgery , Vasodilator Agents/therapeutic use , Ventilators, MechanicalABSTRACT
Transient global amnesia (TGA) was found in 41 of 76 patients admitted to the North Carolina Baptist Hospital with temporary disturbances of memory. Risk factors for stroke were present in 26 (63%) of these 41 patients, and additional risk factors developed in 9 (27%) of the 33 patients available for follow-up. Follow-up evaluation in 33 patients (80%) for periods ranging from 1 to 17 years (mean, 60.3 months) revealed a low rate of recurrence (18%) and a still lower rate of progression to stroke (6%). No transient ischemic attacks were reported during this period. In 2 patients, multiple recurrences of TGA ceased after treatment of the underlying condition (polycythemia in 1 case and myxomatous degeneration of the mitral valve in the other.