Brain diffusion changes in carotid occlusive disease treated with endarterectomy.

BACKGROUND: Patients with unilateral high-grade carotid stenosis or occlusion have been reported to have more leukoaraiosis and ischemic lesions in ipsilateral than in contralateral cerebral hemisphere. The lesions alter apparent diffusion coefficient (ADC) values in diffusion-weighted MRI (DWI). The overall effects of carotid endarterectomy on ADC values have not yet been explored. OBJECTIVE: S: To find out whether 1) average ADC (ADC(av)) values differed between hemispheres, 2) diffusion changes induced by carotid endarterectomy could be detected in brain tissue with serial DWI, and 3) patients with asymptomatic carotid stenosis differed from patients with a symptomatic stenosis. METHODS: Forty-five patients (22 with asymptomatic carotid stenosis and 23 with symptomatic carotid stenosis) with unilateral high-grade carotid stenosis underwent DWI before carotid endarterectomy and 3 and 100 days afterward, and 45 age- and sex-matched healthy control subjects were imaged once. We evaluated ADC(av) values in normal-appearing gray and white matter, watershed regions (WsR), and thalamus. RESULTS: ADC(av) values of ipsilateral white matter and WsR were higher than those of contralateral white matter and WsR, both being higher than in white matter and WsR of control subjects. After carotid endarterectomy, these differences were diminished, but the levels remained higher than in controls. ADC(av) values of gray matter and thalamus remained unaffected. Asymptomatic carotid stenosis and symptomatic carotid stenosis patient groups did not differ from each other. CONCLUSIONS: Carotid stenosis has an effect on diffusion in the white matter of the ipsilateral hemisphere, and it is partly reversible by carotid endarterectomy. The finding may be associated with leukoaraiotic development ("preleukoaraiosis").

Effect of nimodipine on final infarct volume after acute ischemic stroke.

Placebo-controlled clinical trials with nimodipine in acute ischemic stroke have not fulfilled the early optimistic expectations. Nimodipine has in some experimental studies, when administered either before or up to 90 min after induction of cerebral ischemia, resulted in a reduction of infarct size. No studies on the effects of nimodipine on infarct size in man have been published. We measured the infarct volumes in the admission and control CT examinations 3 weeks to 3 months later in 153 patients who had participated in a multicenter, randomized and placebo-controlled study. No statistically significant differences overall were found within or between the treatment groups. Subgroup analyses revealed in the placebo, but not in the nimodipine arm, an increase in the median infarct volumes if the treatment was started within 24 h of onset, and if the volume in the admission CT was less than median. A beneficial effect of nimodipine in prevention of infarct size increase in these circumstances cannot be excluded.

A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke.

BACKGROUND AND PURPOSE: A randomized, double-blind, placebo-controlled multicenter trial was conducted to test the hypothesis that nimodipine would improve the functional outcome in acute ischemic hemispheric stroke. METHODS: A total of 350 patients were randomized to nimodipine 120 mg/d PO or matching placebo for 21 days. Randomization was stratified by onset of therapy, age, and stroke severity. Treatment was begun within 48 hours of onset. The patients had neurological evaluation on admission, on days 1, 7, and 21, and at 3 and 12 months. The primary end points were Rankin grade, neurological score, and mobility at 12 months. RESULTS: We did not find any differences in the functional outcome between the treatment groups or between the stratified subgroups. We were also unable in post hoc analyses to find any groups of patients who benefited from nimodipine. During the first month and at 3 months the case-fatality rate was higher in the nimodipine-treated patients than in those on placebo (P = .004 and P = .030, respectively), but at the 1-year follow-up this difference had lost statistical significance. During the first week nimodipine had a statistically significant lowering effect on both systolic (P = .005) and diastolic (P = .013) blood pressure. CONCLUSIONS: Nimodipine did not improve the functional outcome of acute ischemic hemispheric stroke. The early case-fatality rate was higher in the nimodipine group, possibly due to the blood pressure-lowering effect of nimodipine.

Neuropsychological sequelae of cardiac arrest.

OBJECTIVES: Prospective and community-based studies on the cognitive outcome of out-of-hospital cardiac arrest have not been published. We studied prospectively the neuropsychological sequelae of cardiac arrest and evaluated the effects of nimodipine on them. DESIGN: Placebo-controlled, randomized, double-blind trial of nimodipine compared with placebo in out-of-hospital ventricular fibrillation. SETTING: Urban area of 500,000 inhabitants served by the physician-manned Advanced Life Support Unit of Helsinki. PATIENTS: A total of 155 successfully resuscitated consecutive patients out of 677 resuscitation attempts during 2 1/2 years. Sixty-eight survivors were examined by a neuropsychologist and a neurologist. MAIN OUTCOME MEASURE: Neuropsychological outcome 3 months and 1 year after cardiac arrest. INTERVENTIONS: Nimodipine or placebo at a dosage of 10 micrograms/kg as an intravenous injection immediately after restoration of spontaneous circulation, followed by an infusion of 0.5 micrograms/kg per minute for 24 hours. RESULTS: Three months after cardiac arrest, 41 (60%) of 68 patients were found to have moderate to severe cognitive deficits. At 12 months, 26 (48%) of 54 survivors still had moderate to severe deficits, and the Symptom Check List 90--Revised score indicated the presence of depression in 22 patients (45%) and severe depression in 12 patients (24%). CONCLUSIONS: Moderate to severe neuropsychological sequelae of out-of-hospital cardiac arrest are still present in approximately one half of the survivors at 1 year and may be permanent. There seems to be no excess of increased disability in the subgroup of patients with delayed advanced life support. Nimodipine failed to show any effect on the cognitive functions tested.

Nimodipine after resuscitation from out-of-hospital ventricular fibrillation. A placebo-controlled, double-blind, randomized trial.

One hundred fifty-five consecutive patients resuscitated after out-of-hospital ventricular fibrillation by a physician-manned advanced life support unit were randomly assigned to receive nimodipine or placebo at a dosage of 10 micrograms/kg as an intravenous injection immediately after restoration of spontaneous circulation, followed by an infusion of 0.5 micrograms/kg per minute for 24 hours. No significant difference was found in the 1-year survival rate of nimodipine-treated (30 [40%] of 75 patients) and placebo-treated patients (29 [36%] of 80 patients). Recurrent ventricular fibrillation during the treatment occurred in one patient in the nimodipine group compared with 12 patients in the placebo group. In a post hoc analysis of patients with very long delays in advanced life support (more than 10 minutes), the 1-year survival rate was higher with nimodipine (eight [47%] of 17 patients) than with placebo (two [8%] of 26 patients). Nimodipine may be of benefit in patients with delayed resuscitation.