Delayed Shrinkage of the Brain After Ischemic Stroke: Preliminary Observations With Voxel-Guided Morphometry

Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials. We performed a randomized, double-blind trial of intravenous recombinant tissue plasminogen activator (t-PA) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke. The trial had two parts. Part 1 (in which 291 patients were enrolled) tested whether t-PA had clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke. Part 2 (in which 333 patients were enrolled) used a global test statistic to assess clinical outcome at three months, according to scores on the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS: In part 1, there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours, although a benefit was observed for the t-PA group at three months for all four outcome measures. In part 2, the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed (global odds ratio for a favorable outcome, 1.7; 95 percent confidence interval, 1.2 to 2.6). As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo (P < 0.001). Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group (P = 0.30). Despite an increased incidence of symptomatic intracerebral hemorrhage, treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months.

This study investigates water diffusion changes in Wallerian degeneration. We measured indices derived from the diffusion tensor (DT) and T2-weighted signal intensities in the descending motor pathways of patients with small chronic lacunar infarcts of the posterior limb of the internal capsule on one side. We compared these measurements in the healthy and lesioned sides at different levels in the brainstem caudal to the primary lesion. We found that secondary white matter degeneration is revealed by a large reduction in diffusion anisotropy only in regions where fibers are arranged in isolated bundles of parallel fibers, such as in the cerebral peduncle. In regions where the degenerated pathway crosses other tracts, such as in the rostral pons, paradoxically there is almost no change in diffusion anisotropy, but a significant change in the measured orientation of fibers. The trace of the diffusion tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary fiber loss where the increase in trace is considerably higher. We show that DT-MRI is more sensitive than T2-weighted MRI in detecting Wallerian degeneration. Significant diffusion abnormalities are observed over the entire trajectory of the affected pathway in each patient. This finding suggests that mapping degenerated pathways noninvasively with DT-MRI is feasible. However, the interpretation of water diffusion data is complex and requires a priori information about anatomy and architecture of the pathway under investigation. In particular, our study shows that in regions where fibers cross, existing DT-MRI-based fiber tractography algorithms may lead to erroneous conclusion about brain connectivity.