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on behalf of the MAST-E GroupBackground and Purpose-Hemorrhagic transformation (HT) is the most critical complication of thrombolytics in clinical trials in acute stroke. The aim of this study was to determine the rates and the predictors of HT in the Multicenter Acute Stroke Trial-Europe (MAST-E) study. Methods-We performed a post hoc analysis of MAST-E data designed to assess the safety and efficacy of streptokinase administered intravenously within 6 hours of stroke onset. HT included all intracerebral hemorrhages and symptomatic hemorrhages (SHT) associated with clinical worsening. The predictors of HT and SHT were determined using multivariate modeling. Results-Among the 310 patients included, 159 patients had HT and 37 SHT (97 and 33 in the streptokinase group and 62 and 4 in the placebo group, respectively). Patients with SHT had significantly more atrial fibrillation, diabetes mellitus, no heparin use, streptokinase treatment, and early CT signs. In the multivariate analysis, HT was predicted by early CT signs and streptokinase treatment. SHT was predicted by diabetes mellitus, early CT signs, streptokinase treatment, and the interaction between streptokinase treatment and decreased level of consciousness. Among the streptokinase-treated patients, the same predictors remained. Conclusions-The relative risks of HT after streptokinase were in the same range in MAST-E as in other streptokinase and tPA trials. Early CT signs were strong predictors of both HT and SHT, stressing that these patients are at high risk of bleeding. In our study, the predictors of HT and SHT were similar to those of tPA trials in acute stroke. (Stroke. 1999;30:1326-1332.)

While experimental studies in the monkey have shown that motor recovery after partial destruction of the hand motor cortex was based on adjacent motor reorganization, functional MRI (fMRI) studies with isolated primary motor cortical stroke have not yet been reported in humans. Based on experimental data, we designed a study to test if recovery after stroke within primary motor cortex (M1) was associated with reorganization within the surrounding motor cortex, i.e. the motor cortex was able to vicariate. Since motor recovery is time-dependent and might be inflected according to the tested task, the delay after stroke and two motor tasks were included in our design. We examined four patients with one ischaemic stroke limited to M1, and four sex- and age-matched healthy controls in a temporally balanced prospective longitudinal fMRI study over three sessions: <20 days, 4 months and 2 years after stroke. The paradigm included two motor tasks, finger tapping (FT) and finger extension (FE). Distinct patterns of motor activation were observed with time for FT and FE. At the first session, FT-related activation was lateralized in the ipsilateral hemisphere while FE-related activation was contralateral, involving bilateral cerebellar regions for both tasks. From 4 months, skilled motor recovery was associated with contralateral dorsal premotor and sensorimotor cortex and ipsilateral cerebellum motor-related activations, leading to lateralized motor patterns for both tasks. For the left recovered hand, FT and FE-related activations within M1 were more dorsal in patients than in controls. This dorsal shift progressively increased over 2 years, reflecting functional reorganization in the motor cortex adjacent to the lesion. In addition, patients showed a reverse representation of FT and FE within M1, corresponding to a greater dorsal shift for FT than for FE. This functional dissociation might reflect the structural subdivision of M1 with two distinct finger motor representations within M1. Recovery of FT, located within the lesioned depth of the rolandic sulcus in controls, might be related to the re-emergence of a new representation in the intact dorsal M1, while FE, located more dorsally, underwent minor reorganization. This is the first fMRI study of humans presenting with isolated M1 stroke comparable with experimental lesions in animals. Despite the small number of patients, our findings showing the re-emergence of a fingers motor task in the intact dorsal M1 instead of in ventral M1 are consistent with 'vicariation' models of stroke recovery.

The exploration of brain networks with resting-state fMRI (rs-fMRI) combined with graph theoretical approaches has become popular, with the perspective of finding network graph metrics as biomarkers in the context of clinical studies. A preliminary requirement for such findings is to assess the reliability of the graph based connectivity metrics. In previous test-retest (TRT) studies, this reliability has been explored using intraclass correlation coefficient (ICC) with heterogeneous results. But the issue of sample size has not been addressed. Using the large TRT rs-fMRI dataset from the Human Connectome Project (HCP), we computed ICCs and their corresponding p-values (applying permutation and bootstrap techniques) and varied the number of subjects (from 20 to 100), the scan duration (from 400 to 1200 time points), the cost and the graph metrics, using the Anatomic-Automatic Labelling (AAL) parcellation scheme. We quantified the reliability of the graph metrics computed both at global and regional level depending, at optimal cost, on two key parameters, the sample size and the number of time points or scan duration. In the cost range between 20% to 35%, most of the global graph metrics are reliable with 40 subjects or more with long scan duration (14min 24s). In large samples (for instance, 100 subjects), most global and regional graph metrics are reliable for a minimum scan duration of 7min 14s. Finally, for 40 subjects and long scan duration (14min 24s), the reliable regions are located in the main areas of the default mode network (DMN), the motor and the visual networks.

Background and Purpose-Determining cognitive dysfunctioning (CDF) after stroke is an important issue because it influences choices for management in terms of return to previous activities. Because previous research in subacute stroke has shown important variations in CDF rates, we aimed to describe the frequency and neuropsychological profile of CDF in subacute stroke outside dementia. We used a large battery of tests to screen any potentially hidden CDF. Methods-Patients with Mini-Mental State Examination scores Ն23 were prospectively and consecutively included 2 weeks after a first-ever ischemic brain infarct. Stroke features were based on MRI. Four domains were evaluated: instrumental and executive functions, episodic memory, and working memory (WM). Patients were scored using means and compared with education-and age-matched control subjects. Then we attributed Z-scores for each test and each domain. The most relevant cognitive tests characterizing CDF were determined using logistic regression.

Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected (99m)Tc-HMPAO-labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at 2 and 20 h after injection) and histology were performed. A higher activity was observed in the right damaged hemisphere of the MCAo group [6.5 +/- 0.9 x 10(-3) % of injected dose (ID)/g] than in the control group (3.6 +/- 1.2 x 10(-3) %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher than that observed in the contralateral hemisphere at 2 h after injection (11.6 +/- 2.8 vs. 9.8 +/- 1.7 x 10(-3) %ID/g). Following an initial hMSC lung accumulation, there was a decrease in pulmonary activity from 2 to 20 h after injection in both groups. The spleen was the only organ in which activity increased between 2 and 20 h. The presence of hMSC was documented in the spleen, liver, lung, and brain following histology. IV-injected hMSC are transiently trapped in the lungs, can be sequestered in the spleen, and are predominantly eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial route for a clinical trial of tolerance.

Background and Purpose-Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke. Methods-Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls. Across the entire brain, we compared task-related activity patterns in good and poor recovery and assessed the magnitude of spatial shifts in sensorimotor activity in cortical motor areas after stroke. Results-When compared with healthy controls, patients showed higher activation likelihood estimation values in contralesional primary motor soon after stroke that abated with time, but were not related to motor outcome. The observed activity changes were consistent with restoration of typical interhemispheric balance. In contrast, activation likelihood estimation values in ipsilesional medial-premotor and primary motor cortex were associated with good outcome, reorganization that may reflect vicarious processes associated with ventral activity shifts from BA4a to 4p. In the anterior cerebellum, a novel finding was the association of poor recovery with increased vermal activity, possibly reflecting behaviorally inadequate compensatory strategies engaging the fastigio-thalamo-cortical and corticoreticulospinal systems. Conclusions-Activity in ipsilesional primary

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