Objectives To investigate whether an imaging measure of corticospinal tract (CST) injury in the acute phase can predict motor outcome at 3 month in comparison to clinical assessment of initial motor impairment. Methods A two-site prospective cohort study followed up a group of first-ever ischemic stroke patients using the Upper-Extremity Fugl-Meyer (UE-FM) Scale to measure the motor impairment in the acute phase and at 3 months. A weighted CST lesion load (wCST-LL) was calculated by overlaying the patient’s lesion map on MRI with a probabilistic CST constructed from healthy control subjects. Regression models were fit to assess the predictive value of wCST-LL and compared with initial motor impairment. Results 76 patients (37 from cohort 1 and 39 from cohort 2) completed the study. wCST-LL correlated motor impairment at 3 months measured by UE-FM scale, similar to the clinical assessment of initial motor impairment in both cohort 1 (R2=0.69 vs. R2=0.67, p=0.43) and cohort 2 (R2=0.69 vs. R2=0.62, p=0.25). In the severely impaired subgroup (defined as UE-FM ≤10 at baseline), wCST-LL correlated outcomes significantly better than clinical assessment (R2=0.47 vs. R2=0.11, p=0.03). In the non-severely impaired subgroup, stroke patients recovered approximately 70% of their maximal recovery potential. All stroke patients in both cohorts had poor motor outcomes at 3 months (defined as UE-FM≤25) when wCST-LL was ≥7.0 cc (positive predictive value is 100%). Interpretation wCST-LL, a potential imaging biomarker from the acute phase, can predict post-stroke motor outcomes at 3 months, especially in patients with severe impairment at baseline.

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Background and purpose Transcranial direct current stimulation (tDCS) has shown mixed results in post-stroke motor recovery, possibly because of tDCS dose differences. The purpose of this meta-analysis was to explore whether the outcome has a dose–response relationship with various dose-related parameters. Methods The literature was searched for double-blind, randomized, sham-controlled clinical trials investigating the role of tDCS (≥5 sessions) in post-stroke motor recovery as measured by the Fugl-Meyer Upper Extremity (FM-UE) scale. Improvements in FM-UE scores were compared between active and sham groups by calculating standardized mean differences (Hedge’s g) to derive a summary effect size. Inverse-variance-weighted linear meta-regression across individual studies was performed between various tDCS parameters and Hedge’s g to test for dose–response relationships. Results Eight studies with total of 213 stroke subjects were included. Summary Hedge’s g was statistically significant in favor of the active group (Hedge’s g = 0.61, p = 0.02) suggesting moderate effect. Specifically, studies that used bihemispheric tDCS montage (Hedge’s g = 1.30, p = 0.08) or that recruited chronic stroke patients (Hedge’s g = 1.23, p = 0.02) showed large improvements in the active group. A positive dose–response relationship was found with current density (p = 0.017) and charge density (p = 0.004), but not with current amplitude. Moreover, a negative dose–response relationship was found with electrode size (p < 0.001, smaller electrodes were more effective). Conclusions Our meta-analysis and meta-regression results suggest superior motor recovery in the active group when compared to the sham group and dose–response relationships relating to electrode size, charge density and current density. These results need to be confirmed in future dedicated studies.

Background and Objective A prior meta-analysis revealed that higher doses of transcranial direct current stimulation (tDCS) have a better post-stroke upper-extremity motor recovery. While this finding suggests that currents greater than the typically used 2 mA may be more efficacious, the safety and tolerability of higher currents have not been assessed in stroke patients. We aim to assess the safety and tolerability of single session of up to 4 mA in stroke patients. Methods We adapted a traditional 3+3 study design with a current escalation schedule of 1≫2≫2.5≫3≫3.5≫4 mA for this tDCS safety study. We administered one 30-minute session of bihemispheric montage tDCS and simultaneous customary occupational therapy to patients with first-ever ischemic stroke. We assessed safety with pre-defined stopping rules and investigated tolerability through a questionnaire. Additionally, we monitored body resistance and skin temperature in real-time at the electrode contact site. Results Eighteen patients completed the study. The current was escalated to 4 mA without meeting the pre-defined stopping rules or causing any major safety concern. 50% of patients experienced transient skin redness without injury. No rise in temperature (range 26°C–35°C) was noted and skin ba rrier function remained intact (i.e. body resistance >1 kΩ). Conclusion Our phase I safety study supports that single session of tDCS with current up to 4 mA is safe and tolerable in stroke patients. A phase II study to further test the safety and preliminary efficacy with multi-session tDCS at 4 mA (as compared with lower current and sham stimulation) is a logical next step.

Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.

Background and Purpose— Elevated blood pressure is common in acute stage of ischemic stroke and the strategy to manage this situation is not well established. We therefore conducted a meta-analysis of randomized controlled trials comparing active blood pressure lowering and control groups in early ischemic stroke. Methods— Pubmed, EMBASE, and Clinicaltrials.gov from January 1966 to March 2015 were searched to identify relevant studies. We included randomized controlled trials with blood pressure lowering started versus control within 3 days of ischemic stroke onset. The primary outcome was unfavorable outcome at 3 months or at trial end point, defined as dependency or death, and the key secondary outcome was recurrent vascular events. Pooled relative risks and 95% confidence intervals were calculated using random-effects model. Results— The systematic search identified 13 randomized controlled trials with 12 703 participants comparing early blood pressure lowering and control. Pooling the results with the random-effects model showed that blood pressure lowering in early ischemic stroke did not affect the risk of death or dependency at 3 months or at trial end point (relative risk, 1.04; 95% confidence interval, 0.96–1.13; P =0.35). Also, blood pressure lowering also had neutral effect on recurrent vascular events, as well as on disability or death, all-cause mortality, recurrent stroke, and serious adverse events. Conclusions— This meta-analysis suggested blood pressure lowering in early ischemic stroke had a neutral effect on the prevention of death or dependency.

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Despite the success of reperfusion therapy in significantly reducing the extent of infarct expansion after stroke, the effect of revascularization on poststroke neuroinflammation and the role of anti-inflammatory strategies in postreperfusion era are yet to be explored. Here, we investigate whether the neuroinflammatory response may still contribute to neurologic deficits after reperfused stroke by using targeted complement inhibition to suppress poststroke neuroinflammation in mice with or without concurrent reperfusion therapy. Complement inhibition was achieved using B4Crry, an injury site-targeted inhibitor of C3 activation. Following embolic stroke in male C57bl/6 mice, thrombolysis using tissue-plasminogen activator (t-PA) reduced injury and improved motor deficits, but did not improve cognitive outcomes. After both reperfused and non-reperfused stroke, complement activation and opsonization of hippocampal synapses directed ongoing microglia-dependent phagocytosis of synapses for at least 30 d after stroke, leading to a loss of synaptic density that was associated with cognitive decline. B4Crry treatment, alone or in combination with tPA, limited perilesional complement deposition, reduced microgliosis and synaptic uptake, and improved cognitive outcome without affecting regenerative responses. Furthermore, complement inhibition improved the safety, efficacy, and treatment window of reperfusion therapy with t-PA by limiting hemorrhagic transformation. This work thus demonstrates that poststroke neuroinflammation contributes to hemorrhagic transformation and progression of neurodegenerative responses in the brain even following early and successful revascularization.