Distal Versus Proximal Arm Improvement After Paired Vagus Nerve Stimulation Therapy After Chronic Stroke.

To evaluate differences in upper-extremity (UE) segment-specific (proximal or distal segment) recovery after vagus nerve stimulation (VNS) paired with UE rehabilitation (Paired-VNS) compared with rehabilitation with sham-VNS (Control). We also assessed whether gains in specific UE segments predicted clinically meaningful improvement. This study reports on a secondary analysis of Vagus nerve stimulation paired with rehabilitation for UE motor function after chronic ischemic stroke (VNS-REHAB), a randomized, triple-blinded, sham-controlled pivotal trial. A Rasch latent regression was used to determine differences between Paired-VNS and Controls for distal and proximal UE changes after in-clinic therapy and 3 months later. Subsequently, we ran a random forest model to assess candidate predictors of meaningful improvement. Each item of the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) was evaluated as a predictor of response to treatment. Nineteen stroke rehabilitation centers in the USA and UK. Dataset included 108 participants (N=108) with chronic ischemic stroke and moderate-to-severe UE impairments. Not applicable. FMA-UE and WMFT. Distal UE improvement was significantly greater in the Paired-VNS group than in Controls immediately after therapy (95% confidence interval, 0.27-0.73; P≤.001) and after 3 months (95% confidence interval, 0.16-0.75; P=.003). Both groups showed similar improvement in proximal UE at both time points. A subset of both distal and proximal items from the FMA-UE and WMFT were predictors of meaningful improvement. Paired-VNS improved distal UE impairment in chronic stroke to a greater degree than intensive rehabilitation alone. Proximal improvements were equally responsive to either treatment. Given that meaningful UE recovery is predicted by improvements across both proximal and distal segments, Paired-VNS may facilitate improvement that is otherwise elusive.

Vora I ，Gochyyev P ，Engineer N ，Wolf SL ，Kimberley TJ ... -  《-》

Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.

Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures. Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain). Eight clinical measures assessed at baseline were also evaluated (treatment group, age, race, gender, paretic side, pre-stroke dominant hand, time since stroke, and baseline Fugl-Meyer upper extremity score). Bivariate analyses compared each measure with the primary trial end point (change in Fugl-Meyer upper extremity score from baseline to end of 6 weeks of treatment) across all subjects, with secondary analyses examining trial groups separately. MRIs were available from 80 patients (age = 59.8 ± 9.5 years, 29 women). Across all patients, less white matter hyperintensities (r = -0.25, p = 0.028) at baseline was associated with larger Fugl-Meyer score change. In the VNS group, less white matter hyperintensities (r = -0.37, p = 0.018) and larger ipsilesional thalamus volume (r = 0.33, p = 0.046) were each associated with larger Fugl-Meyer score change. Analysis of covariance (ANCOVA) analyses tested the interaction that each baseline measure had with treatment group and found that the model examining white matter hyperintensities had a significant interaction term, indicating 2.3 less change in Fugl-Meyer Upper Extremity (FM-UE) points in the VNS group relative to the control group for each point increase in modified Fazekas scale. Neuroimaging measures are associated with extent of gains on the primary endpoint of a phase III stroke recovery trial. Among the neuroimaging measures examined, a measure of global brain health (extent of white matter hyperintensities) was better at explaining the change in arm impairment as compared with measures of regional injury; this was true when examining all study subjects as well as only those in the VNS group and is consistent with the global mechanism of action that VNS has throughout the cerebrum. Future studies can evaluate additional measures that further predict response to VNS therapy. The current findings suggest that individual patient neuroimaging results may be useful for a personalized medicine approach to stroke recovery therapeutics. ANN NEUROL 2024.

Schwarz A ，Feldman M ，Le V ，Dawson J ，Liu CY ，Francisco GE ，Wolf SL ，Dixit A ，Alexander J ，Ali R ，Brown BL ，Feng W ，DeMark L ，Hochberg LR ，Kautz SA ，Majid A ，O'Dell MW ，Redgrave J ，Turner DL ，Kimberley TJ ，Cramer SC ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Examining the effectiveness of motor imagery combined with non-invasive brain stimulation for upper limb recovery in stroke patients: a systematic review and meta-analysis of randomized clinical trials.

Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are common non-invasive brain stimulation (NIBS) methods for functional recovery after stroke. Motor imagery (MI) can be used in the rehabilitation of limb motor function after stroke, but its effectiveness remains to be rigorously established. Furthermore, there is a growing interest in the combined application of NIBS with MI, yet the evidence regarding its impact on the recovery of upper limb function after stroke is inconclusive. This meta-analysis aimed to demonstrate whether combining the two is superior to NIBS alone or MI alone to provide a reference for clinical decision-making. PubMed, EMBASE, Cochrane Library, Web of Science, Science Direct, CNKI, WANFANG, and VIP databases were searched for randomized controlled trials on the effects of MI combined NIBS in motor function recovery after stroke until February 2024. The outcomes of interest were associated with body functions or structure (impairment) and activity (functional). The primary outcome was assessed with the Fugl-Meyer assessment of the upper extremity (FMA-UE) for motor function of the upper limbs and the modified Barthel Index (MBI) for the ability to perform daily living activities. For secondary outcomes, functional activity level was measured using wolf motor function test (WMFT) and action research arm test (ARAT), and cortical excitability was assessed using cortical latency of motor evoked potential (MEP-CL) and central motor conduction time (CMCT). The methodological quality of the selected studies was evaluated using the evidence‑based Cochrane Collaboration's tool. A meta-analysis was performed to calculate the mean differences (MD) or the standard mean differences (SMD) and 95% confidence intervals (CI) with random-effect models. A total of 14 articles, including 886 patients, were reviewed in the meta-analysis. In comparison with MI or NIBS alone, the combined therapy significantly improved the motor function of the upper limbs (MD = 5.43; 95% CI 4.34-6.53; P < 0.00001) and the ability to perform activities of daily living (MD = 11.07; 95% CI 6.33-15.80; P < 0.00001). Subgroup analyses showed an interaction between the stage of stroke, the type of MI, and the type of NIBS with the effect of the combination therapy. The combination of MI and NIBS may be a promising therapeutic approach to enhance upper limb motor function, functional activity, and activities of daily living after stroke. PROSPERO registration CRD42023493073.

Zhang W ，Li W ，Liu X ，Zhao Q ，Gao M ，Li Z ，Lv P ，Yin Y ... -  《Journal of NeuroEngineering and Rehabilitation》

Repetitive Transcranial Magnetic Stimulation for Motor Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials With Low Risk of Bias.

Zhang JJY ，Ang J ，Saffari SE ，Tor PC ，Lo YL ，Wan KR ... -  《-》