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.