Abstract
In a randomized double-blind placebocontrolled study of 27 patients with acute ischemic stroke, the effect on regional CMRglc (rCMRglc) of the calcium channel blocking agent nimodipine administered in addition to routine treatment was investigated. Following computed tomography-supported diagnosis of focal ischemia in the middle cerebral artery territory, positron emission tomography (PET) of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) was performed, and the patients were entered into the study within 48 h after onset of symptoms, randomly receiving either nimodipine (2 mg/h constant i.v. infusion for 5 days, 120 mg/day orally for another 16 days) or carrier/placebo. FDG PET was repeated after completion of therapy. The clinical course was followed during the treatment period and for 6 months after the stroke, using the Mathew Score for early and the Barthel Index for late assessment. During that observation period, five patients died in the nimodipine group and four in the control group. Subsequently, the code was broken, and the clinical and PET data were analyzed in relation to treatment assignment, with the nimodipine group comprising 11 and the control group 12 eligible cases. The two groups were similar with respect to age and sex distribution, initial clinical deficit, and infarct size and location. While the infarct rCMRglc showed comparable slight increases over time in both groups, the metabolic changes in the other evaluated regions (contralateral infarct mirror region, ipsi- and contralateral cerebral gray matter, contra- and ipsilateral cerebellar hemispheres) differed significantly between treatment groups (side x region x treatment interaction p < 0.025). In the control group, major improvement was found only in contralateral cerebrum (7.4%), whereas the nimodipine group had bilaterally increased rCMRglc of morphologically intact cerebral (14.6 and 17.1%, respectively) and, to a lesser degree, cerebellar (6.9 and 10.0%, respectively) structures. Likewise, progress of (postacute) rehabilitation was significantly (p1 < 0.05) better in the nimodipine treated patients (median change of Barthel Index = 40 vs. 2.5), although their clinical improvement during the first 3 weeks did not differ from the controls' (median change of Mathew Score = 12 and 11.5, respectively). These results lend further support to the notion that nimodipine treatment is of benefit in acute ischemic stroke. Since action on the infarct proper is unlikely when the drug is given many hours after the ischemic attack, it may be concluded that nimodipine exerts its beneficial effect by ameliorating the functional impairment of morphologically intact tissue surrounding the focal ischemia and by improving the metabolic deactivation of remote brain structures.