Patient-tailored transcranial direct current stimulation to improve stroke rehabilitation: study protocol of a randomized sham-controlled trial.

BACKGROUND: Many patients do not fully regain motor function after ischemic stroke. Transcranial direct current stimulation (TDCS) targeting the motor cortex may improve motor outcome as an add-on intervention to physical rehabilitation. However, beneficial effects on motor function vary largely among patients within and across TDCS trials. In addition to a large heterogeneity of study designs, this variability may be caused by the fact that TDCS was given as a one-size-fits-all protocol without accounting for anatomical differences between subjects. The efficacy and consistency of TDCS might be improved by a patient-tailored design that ensures precise targeting of a physiologically relevant area with an appropriate current strength. METHODS: In a randomized, double-blinded, sham-controlled trial, patients with subacute ischemic stroke and residual upper-extremity paresis will receive two times 20 min of focal TDCS of ipsilesional primary motor hand area (M1-HAND) during supervised rehabilitation training three times weekly for 4 weeks. Anticipated 60 patients will be randomly assigned to active or sham TDCS of ipsilesional M1-HAND, using a central anode and four equidistant cathodes. The placement of the electrode grid on the scalp and current strength at each cathode will be personalized based on individual electrical field models to induce an electrical current of 0.2 V/m in the cortical target region resulting in current strengths between 1 and 4 mA. Primary endpoint will be the difference in change of Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score between active TDCS and sham at the end of the intervention. Exploratory endpoints will include UE-FMA at 12 weeks. Effects of TDCS on motor network connectivity and interhemispheric inhibition will be assessed with functional MRI and transcranial magnetic stimulation. DISCUSSION: The study will show the feasibility and test the efficacy of personalized, multi-electrode anodal TDCS of M1-HAND in patients with subacute stroke patients with upper-extremity paresis. Concurrent multimodal brain mapping will shed light into the mechanisms of action of therapeutic personalized TDCS of M1-HAND. Together, the results from this trial may inform future personalized TDCS studies in patients with focal neurological deficits after stroke.

The impact of aerobic and resistance training intensity on markers of neuroplasticity in health and disease.

OBJECTIVE: To determine the effects of low- vs. high-intensity aerobic and resistance training on motor and cognitive function, brain activation, brain structure, and neurochemical markers of neuroplasticity and the association thereof in healthy young and older adults and in patients with multiple sclerosis, Parkinson's disease, and stroke. DESIGN: Systematic review and robust variance estimation meta-analysis with meta-regression. DATA SOURCES: Systematic search of MEDLINE, Web of Science, and CINAHL databases. RESULTS: Fifty studies with 60 intervention arms and 2283 in-analyses participants were included. Due to the low number of studies, the three patient groups were combined and analyzed as a single group. Overall, low- (g=0.19, p = 0.024) and high-intensity exercise (g=0.40, p = 0.001) improved neuroplasticity. Exercise intensity scaled with neuroplasticity only in healthy young adults but not in healthy older adults or patient groups. Exercise-induced improvements in neuroplasticity were associated with changes in motor but not cognitive outcomes. CONCLUSION: Exercise intensity is an important variable to dose and individualize the exercise stimulus for healthy young individuals but not necessarily for healthy older adults and neurological patients. This conclusion warrants caution because studies are needed that directly compare the effects of low- vs. high-intensity exercise on neuroplasticity to determine if such changes are mechanistically and incrementally linked to improved cognition and motor function.

Recurrent Ischemic Stroke - A Systematic Review and Meta-Analysis.

OBJECTIVES: Recurrent stroke remains a challenge though secondary prevention is initiated immediately post-stroke. Stroke subtype may determine the risk of recurrent stroke and require specific preventive measures. We aimed to identify subtype-specific stroke recurrence and associated risk factors over time. METHODS AND MATERIALS: A systematic review was performed using PubMed and Embase for studies including adults >18 years, first-ever ischemic stroke in population-based observational studies or registries, documented TOAST-criteria and minimum 1-year follow-up. Meta-analysis on stroke recurrence rate was performed. Final search: November 2019. RESULTS: The search retrieved 26 studies (between 1997 and 2019). Stroke recurrence rate ranged from 5.7% to 51.3%. Recurrent stroke was most frequent in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke with recurrent stroke similar to index stroke subtype. We identified a lower recurrence rate for small vessel occlusion (SVO) stroke with recurrence frequently of another stroke subtype. Based on a meta-analysis the summary proportion recurrence rate of recurrent stroke in studies using TOAST-criteria = 0.12 and = 0.14 in studies using TOAST-like criteria. Hypertension, diabetes mellitus, atrial fibrillation previous transient ischemic attack, and high stroke severity were independent risk factors for recurrence. CONCLUSION: Stroke recurrence rates seem unchanged over time despite the use of secondary prevention. The highest recurrence rate is in LAA and CE stroke eliciting same subtype recurrent stroke. A lower recurrence rate is seen with SVO stroke with a more diverse recurrence pattern. Extensive workup is important in all stroke subtypes - including SVO stroke. Future research needs to identify better preventive treatment and improve compliance to risk factor prevention to reduce stroke recurrence.

Effect of high-intensity training on endothelial function in patients with cardiovascular and cerebrovascular disease: A systematic review.

OBJECTIVES: Exercise improves endothelial dysfunction, the key manifestation of cardiovascular and cerebrovascular disease, and is recommended in both cardiovascular and cerebrovascular rehabilitation. Disagreement remains, however, on the role of intensity of exercise. The purpose of this review was to gather current knowledge on the effects of high-intensity training versus moderate-intensity continuous exercise on endothelial function in cardiovascular and cerebrovascular patients. METHODS: A systematic review was performed in PubMed database, Embase and Cochrane libraries and on PEDro using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were restricted to cardiovascular and cerebrovascular patients, and healthy subjects as general reference. Interventions comprised of high-intensity training alone, high-intensity training compared to moderate-intensity continuous exercise, or no training, with endothelial function as outcome measure. Endothelial function was measured either physiologically by flow-mediated dilatation and/or by systemic biomarkers. Data were analyzed descriptively due to non-comparability for a meta-analysis to be performed. RESULTS: A total of 20 studies were included in the review. Although there was great heterogenecity in design, population and exercise protocols, all studies found high-intensity training to be safe. High-intensity training was equal to moderate-intensity continuous exercise through improvement in endothelial function in 15 of the 20 selected studies, as measured by flow-mediated dilatation, nitric oxide bioavailability and circulating biomarkers. Only a few studies examined high-intensity training in cerebrovascular patients, none with endothelial function as outcome. CONCLUSION: High-intensity training is promising as a time-efficient exercise strategy in cardiovascular rehabilitation, but data on endothelial effects in cerebrovascular rehabilitation are warranted. Agreement on a more uniform exercise protocol is essential to further investigate the optimal exercise mode for cerebrovascular rehabilitation.