Recovery of Walking Function in Stroke Patients: The Copenhagen Stroke Study

Background Individuals with acute-onset central nervous system (CNS) injury, including stroke, motor incomplete spinal cord injury, or traumatic brain injury, often experience lasting locomotor deficits, as quantified by decreases in gait speed and distance walked over a specific duration (timed distance). The goal of the present clinical practice guideline was to delineate the relative efficacy of various interventions to improve walking speed and timed distance in ambulatory individuals greater than 6 months following these specific diagnoses. Methods A systematic review of the literature published between 1995 and 2016 was performed in 4 databases for randomized controlled clinical trials focused on these specific patient populations, at least 6 months postinjury and with specific outcomes of walking speed and timed distance. For all studies, specific parameters of training interventions including frequency, intensity, time, and type were detailed as possible. Recommendations were determined on the basis of the strength of the evidence and the potential harm, risks, or costs of providing a specific training paradigm, particularly when another intervention may be available and can provide greater benefit. Results Strong evidence indicates that clinicians should offer walking training at moderate to high intensities or virtual reality-based training to ambulatory individuals greater than 6 months following acute-onset CNS injury to improve walking speed or distance. In contrast, weak evidence suggests that strength training, circuit (ie, combined) training or cycling training at moderate to high intensities, and virtual reality-based balance training may improve walking speed and distance in these patient groups. Finally, strong evidence suggests that body weight-supported treadmill training, robotic-assisted training, or sitting/standing balance training without virtual reality should not be performed to improve walking speed or distance in ambulatory individuals greater than 6 months following acute-onset CNS injury to improve walking speed or distance. Discussion The collective findings suggest that large amounts of task-specific (ie, locomotor) practice may be critical for improvements in walking function, although only at higher cardiovascular intensities or with augmented feedback to increase patient's engagement. Lower-intensity walking interventions or impairment-based training strategies demonstrated equivocal or limited efficacy. Limitations As walking speed and distance were primary outcomes, the research participants included in the studies walked without substantial physical assistance. This guideline may not apply to patients with limited ambulatory function, where provision of walking training may require substantial physical assistance. Summary The guideline suggests that task-specific walking training should be performed to improve walking speed and distance in those with acute-onset CNS injury although only at higher intensities or with augmented feedback. Future studies should clarify the potential utility of specific training parameters that lead to improved walking speed and distance in these populations in both chronic and subacute stages following injury. Disclaimer These recommendations are intended as a guide for clinicians to optimize rehabilitation outcomes for persons with chronic stroke, incomplete spinal cord injury, and traumatic brain injury to improve walking speed and distance.

Clinical Practice Guideline to Improve Locomotor Function Following Chronic Stroke, Incomplete Spinal Cord Injury, and Brain Injury.

Background and Purpose -Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. Methods -Sixty-one adults with chronic hemiparetic gait after ischemic stroke (6 months)-were randomized to 6 months (3×/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-in-tensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), O2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. Results -Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17%versus 3%, δ%T-AEX versus R-CONTROL, P 0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30%versus 11%, P 0.02) and mobility function indexed by WIQ distance scores (56%versus 12%, P 0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P 0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P 0.05), but not fitness gains. Conclusions -T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: A randomized, controlled trial

Muscle strengthening for hemiparesis after stroke: A meta-analysis.

Background and Purpose—The purpose of this systematic review and meta-analysis was to investigate the effects of exercise training on balance capacity in people in the chronic phase after stroke. F...

Effects of Exercise Therapy on Balance Capacity in Chronic Stroke: Systematic Review and Meta-Analysis.

Endothelial cell dysfunction and diabetic vascular complications are intrinsically linked. Although BDNF plays a protective role in cerebral microvascular complications caused by diabetes, the mechanisms of this activity are not fully clear. In this study, we investigated the role of BDNF in the hyperglycemic injury of BMECs and its associated intracellular signal transduction pathways. BMECs were treated with 33 mM glucose to imitate the endothelium under hyperglycemic conditions. The high-glucose treatment caused cell dysfunction, as evaluated by oxidative stress and cell apoptosis, which could be alleviated by BDNF. In addition, BDNF preserved mitochondrial function as assessed by mPTP opening, mitochondrial membrane potential, calcium content, and mitochondrial biogenesis markers. Western blot analysis of LC3-II, p62, and TOMM20 and the detection of mRFP-GFP-LC3 adenovirus for autophagy flux revealed that BDNF enhanced autophagy flux. Furthermore, BDNF activated mitophagy, which was confirmed by the observed colocalization of LC3-II with BNIP3 and from transmission electron microscopy observations. The HIF-1α/BNIP3 signaling pathway was associated with BDNF/TrkB-induced mitophagy. In addition, BDNF-induced mitophagy played a protective role against BMEC damage under hyperglycemia. Thus, the results of this study suggest that BDNF/TrkB/HIF-1α/BNIP3-mediated mitophagy protects BMECs from hyperglycemia.

BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in angiogenesis and maintenance of endothelial integrity. Whether circulating BDNF levels are associated with von Willebrand factor (vWF) levels, which are indicators of endothelial dysfunction is not known. This study investigated the association between plasma BNDF and vWF levels and whether these biomarkers could predict cardiovascular events at a 12-month follow-up in patients with stable coronary artery disease (CAD). We recruited 234 patients with suspected angina pectoris. Subjects were divided into CAD (n = 143) and control (n = 91) groups based on coronary angiography. Plasma BDNF and vWF levels were measured using ELISA. Patients were followed-up for one year, and information on adverse cardiac events was collected. CAD patients exhibited significantly lower plasma BDNF and higher vWF levels than those of control patients. High vWF levels were associated with low BDNF levels even after adjustment for age, gender, low-density lipoprotein (LDL) levels, and the presence of diabetes mellitus. A receiver operating characteristic curve was used to determine whether low BDNF and high vWF levels could predict adverse cardiovascular events. The area under the curve for vWF and the inverse of BDNF were 0.774 and 0.804, respectively. These findings suggest that endothelial dysfunction is an important determinant of the impaired circulating BDNF levels, and they further reflected cardiovascular prognosis in stable CAD patients.

/pdf/association-between-brain-derived-neurotrophic-factor-and-50t3feemnw.pdf

Association between brain-derived neurotrophic factor and von Willebrand factor levels in patients with stable coronary artery disease.

BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells.

Purpose: To evaluate the effect of aerobic cycling training with lower limb weights on cardiovascular fitness (peak VO2) and walking ability in chronic stroke survivors, and to investigate the relationship between changes in these parameters. Methods: 133 Chinese patients with chronic hemiparetic stroke (mean age 58 years) were randomized to either 8-week (5×/week) aerobic cycling training with lower limb weights group (n = 68) or a low-intensity overground walking group (n = 65). Peak VO2, 6-minute walk distance (6MWD), knee muscle strength, balance and spasticity were measured before and after intervention. Results: Cycling training increased peak VO2 (24% vs. 3%, p < 0.001), 6MWD (2.7% vs. 0.5%, p < 0.001), paretic (11% vs. 1.6%, p < 0.001) and nonparetic knee strength (16% vs. 1.0%, p < 0.001). In the cycling group, percent changes in peak VO2 were positively associated with those in paretic (r = 0.491, p < 0.001) and nonparetic knee strength (r = 0.432, p < 0.001). Increased 6MWD correlated significa...

Intensive aerobic cycling training with lower limb weights in Chinese patients with chronic stroke: discordance between improved cardiovascular fitness and walking ability

Bilei Wang

Papers

BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury.

Association between brain-derived neurotrophic factor and von Willebrand factor levels in patients with stable coronary artery disease.

BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells.

Intensive aerobic cycling training with lower limb weights in Chinese patients with chronic stroke: discordance between improved cardiovascular fitness and walking ability