Background and Purpose-The purpose of this study was to perform a meta-analysis of studies that investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor function in patients with stroke. Methods-We searched for randomized controlled trials published between January 1990 and October 2011 in PubMed, Medline, Cochrane, and CINAHL using the following key words: stroke, cerebrovascular accident, and repetitive transcranial magnetic stimulation. The mean effect size and a 95% CI were estimated for the motor outcome and motor threshold using fixed and random effect models. Results-Eighteen of the 34 candidate articles were included in this analysis. The selected studies involved a total of 392 patients. A significant effect size of 0.55 was found for motor outcome (95% CI, 0.37-0.72). Further subgroup analyses demonstrated more prominent effects for subcortical stroke (mean effect size, 0.73; 95% CI, 0.44 -1.02) or studies applying low-frequency rTMS (mean effect size, 0.69; 95% CI, 0.42-0.95). Only 4 patients of the 18 articles included in this analysis reported adverse effects from rTMS. Conclusions-rTMS has a positive effect on motor recovery in patients with stroke, especially for those with subcortical stroke. Low-frequency rTMS over the unaffected hemisphere may be more beneficial than high-frequency rTMS over the affected hemisphere. Recent limited data suggest that intermittent theta-burst stimulation over the affected hemisphere might be a useful intervention. Further well-designed studies in a larger population are required to better elucidate the differential roles of various rTMS protocols in stroke treatment. (Stroke. 2012;43:1849-1857.)

Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton’s jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton’s jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.

Background and Purpose-Severe asymptomatic carotid stenosis has been associated with cognitive impairment, but it is unknown whether this association is attributable to effects on brain connectivity. We present cognitive network abnormalities in a group of patients at a presymptomatic stage. Methods-Seventeen patients with Ն70% asymptomatic stenosis of unilateral internal carotid artery were compared with 26 healthy controls utilizing a comprehensive neuropsychological battery, the dizziness handicap inventory, and multimodality neuroimaging including diffusion tensor imaging and resting-state functional connectivity magnetic resonance imaging. Longitudinally, assessments were completed in a subgroup of 10 patients at 3 months after carotid artery stenting. Results-Compared with the healthy controls, the patients had worse dizziness scores, poorer memory, complex visuo-spatial performances, and lower whole-brain mean fractional anisotropy. The Scheltens scores of leukoaraiosis/ infarction were not different between groups. Their seed-based functional connectivity magnetic resonance imaging showed marked decrements of interhemispheric and intrahemispheric, ipsilaterally to carotid stenosis, functional connectivity in the frontoparietal network. In the default mode network, the intrahemispheric functional connectivity was bilaterally impaired. Importantly, the disrupted mean fractional anisotropy in the patients significantly correlated with the attention and verbal memory functions. After successful carotid artery stenting, small but measurable increments of the mean fractional anisotropy and little functional connectivity in the default mode network ipsilateral-to-carotid artery stenting were noted. Conclusions-We identified for the first time distinct patterns of network disruption that correlate with cognitive fragility in patients with asymptomatic carotid stenosis. Brain connectivity may provide early and useful biomarkers for brain ischemia and reperfusion. (Stroke. 2012;43:2567-2573.)Key Words: asymptomatic carotid stenosis Ⅲ cognitive impairment Ⅲ diffusion tensor imaging Ⅲ endovascular treatment Ⅲ functional connectivity magnetic resonance imaging Ⅲ resting state Ⅲ stent A symptomatic stenosis of the internal carotid artery (ICA) is described as significant atherosclerosis without stroke or transient ischemic attack in the brain or eyes. 1 Retrospective studies comparing asymptomatic subjects with and without ultrasound-assessed carotid stenosis have shown that subjects with carotid stenosis had significantly poorer performance in tests of attention, psychomotor speed, and memory. [2][3][4] Moreover, severe ICA stenosis (Ն50%) has been associated with a higher prevalence of silent cerebral infarcts and white matter hyperintensities, 3 indicating that "asymptomatic" carotid stenosis may not be truly asymptomatic. To understand the pathological changes after chronic cerebral hypoperfusion, experimental models of vascular cognitive impairment have been induced by bilateral 5 or unilateral 6 common carotid a...

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3–6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents.