American Heart Association


Higher Intensity, Higher Dose Aerobic Exercise Training After Stroke

Kate Hayward, PhD, PT

Klassen TD, Dukelow SP, Bayley MT, Benavente O, Hill MD, Krassioukov A, Liu-Ambrose T, Pooyania S, Poulin MJ, Schneeberg A, et al. Higher Doses Improve Walking Recovery During Stroke Inpatient Rehabilitation. Stroke. 2020;51:2639-2648.

Stroke recovery and rehabilitation trials have received much criticism for underdosing the tested intervention,1 which remains an important consideration when interpreting past trials in the field.2

In this trial of aerobic exercise during inpatient rehabilitation by Klassen et al.,3 the intensity (heart rate reserve during training and walking steps) and amount (minutes of training) of aerobic exercise were increased from usual care. The control group (usual care) typically received 1 hour, 5 days/week, while the Determining Optimal Post-Stroke Exercise 1 (DOSE1) group received 1 hour, 5 days/week (with a target of double the intensity of the control group), and the DOSE2 group received 2 hours, 5 days/week (with a target of quadruple the intensity of the control group), each for a 4-week duration (20 sessions).

Article Commentary: “Movement Behavior Patterns in People With First-Ever Stroke”

Tamaya Van Criekinge, PT

Wondergem R, Veenhof C, Wouters EMJ, de Bie RA, Visser-Meily JMA, Pisters MF. Movement Behavior Patterns in People With First-Ever Stroke. Stroke. 2019;50:3553–3560.

Are you reaching the recommended daily step goal of 10,000 steps for achieving a desirable level of physical activity? During routine daily activities, this is already considered a difficult task, and it becomes harder when having to deal with activity impairments. People living with stroke spend only half of the recommended time being active as compared to healthy individuals and are subsequently at high risk of developing sedentary behavior. Since prolonged sedentary behavior can damage your physical and mental health, it is important to gain insight into these unhealthy movement behavior patterns of people living with stroke. As the authors suggest, this provides health care providers with important information regarding the identification of the right persons with specific behaviors for targeted interventions.

Article Commentary: “Contributions of Stepping Intensity and Variability to Mobility in Individuals Poststroke: A Randomized Clinical Trial”

Tamaya Van Criekinge, PT

Hornby TG, Henderson CE, Plawecki A, Lucas E, Lotter J, Holthus M, et al. Contributions of Stepping Intensity and Variability to Mobility in Individuals Poststroke: A Randomized Clinical Trial. Stroke. 2019;50:2492–2499.

Recovery of gait after stroke is considered one of the most important therapy goals for both patients and therapists, to assure independency and the ability to ambulate in the community. However, over 20% of stroke survivors do not reach independent walking, which necessitates the implementation of more intensive gait rehabilitation strategies. As Hornby et al. correctly state, rehabilitation staff are often too reserved, as they are scared of potential adverse effects, such as cardiovascular events and abnormal kinematic movements strategies.

In this study, Hornby and colleagues questioned if the benefits after high-intensity training in motor recovery outweigh the possible adverse events. In total, 97 chronic stroke patients were randomized in three groups: 1) High-intensity in high variable contexts (speed-dependent and skill-dependent multiple direction treadmill training, overground training and stair climbing at 70-80% of the heart rate reserve); 2) High-intensity with minimal variability (forward stepping treadmill and overground training at 70-80% of heart rate reserve); and 3) Low-intensity in high variable contexts (similar variable contexts as group one, yet performing exercises at 30-40% of heart rate reserve). Primary walking outcomes assessed were self-selected and fasted speed, single-limb stance and step-length asymmetry at self-selected and fasted speed, and six-minute walking test at fasted speed.

Recovery Post-Stroke: Proportional or Not?

Kathryn S. Hayward, PhD, PT

Hawe RL, Scott SH, Dukelow SP. Taking Proportional Out of Stroke Recovery. Stroke. 2019;50:204–211.

In this entry, I discuss a recent publication by Rachel Hawe and colleagues (1) regarding the potential biases of the mathematical properties of the proportional recovery rule and how this may impact application in the field of stroke recovery. Proportional recovery is the idea that most individuals post-stroke (“fitters” to the rule) will recover 70% of their potential on a given outcome (see paper for rule equation). The authors cite multiple studies that have demonstrated proportional recovery for upper limb motor impairment using a single outcome (Fugl Meyer Upper Limb assessment, out of 66 points), and recent work extending this rule to lower limb, aphasia and hemispatial neglect recovery outcomes.

The principal mathematical concept discussed as a limitation of the proportional recovery rule is mathematical coupling. This concept refers to when one variable directly or indirectly contains all or a part of another. For example, in the case of proportional recovery of the upper limb post-stroke, the initial score on Fugl Meyer Upper Limb assessment is part of both the independent and dependent variables of the proportional recovery rule.

Is Circuit Training Useful After Stroke?

Stephen Makin, PhD

English C, Hillier S, Lynch E. Circuit Class Therapy for Improving Mobility After Stroke. Stroke. 2017

There are few things in life I find more boring than going to the gym. Running on a treadmill or lifting weights for what seems like hours just doesn’t interest me.

Circuit class can be fun though. You get to try lots of different exercises and move onto the next one before they get boring.

But could they also work in the stroke unit gym? After all, that’s nothing like a usual gym.

This is something people have been asking for a while. The first study of circuit training in stroke rehabilitation was carried out in 2000. English and colleagues have updated the Cochrane review on circuit training after stroke.

Breakthroughs in Neurorehabilitation: Using Brain Computer Interfaces for Stroke Recovery

Gurmeen Kaur, MBBS

Bundy DT, Souders L, Baranyai K, Leonard L, Schalk G, Coker R, et al. Contralesional Brain–Computer Interface Control of a Powered Exoskeleton for Motor Recovery in Chronic Stroke Survivors. Stroke. 2017

Brain computer interfaces (BCIs) are defined as systems which take biological signal from a person and predict some abstract aspect of the person’s cognitive state. The goal of the BCI technology is to give severely paralyzed people a way to communicate.

While BCIs can use several input-signals, including EEG, EMG, and fMRIs, the BCI technology developed for chronic stroke rehabilitation has been focused on demonstrating motor improvement with the use of EEG input. Recent studies have shown that BCI-controlled orthoses or functional electric stimulators can lead to improvements in motor function in chronic stroke survivors.

In this study, the authors recruited 10 subjects with chronic hemiparesis involving the upper extremity for a home-based BCI powered exoskeleton. Previous experimenters had used EEG signals derived from “perilesional” cortex, contralateral to the arm involvement—which means the area next to that affected by the stroke. The problem with use of perilesional cortex was that if the infarct size is large, with extensive cortical damage, the perilesional cortex was not able to produce sufficient EEG signal to power the exoskeleton. To overcome this, the authors used “contralesional” cortex, ipsilateral to the affected arm. This is the first study to look at the use of the unaffected hemicortex in chronic stroke recovery and aimed to see if plasticity could be triggered.

Discovering the Role of Ipsilesional Parietofrontal Motor Circuits in Stroke and Motor Recovery Through Functional Brain Imaging

Danny R. Rose, Jr., MD

The advent of functional brain imaging has greatly advanced the understanding of how interregional interactions and connectivity in the brain are disrupted by ischemic stroke and are modified in patients as they recover motor function after stroke. Most studies have focused on frontal motor circuits, including the primary motor cortices (M1), dorsal (PMd) and ventral premotor cortices (PMv), and the supplementary motor area (SMA). Studies in healthy subjects suggest that the posterior parietal cortices also play an important role in motor tasks, particularly dexterous hand function which is crucial for functional activities. Data from both resting-state connectivity studies and longitudinal whole-brain analyses suggest a reduced information flow from the ipsilesional parietal brain regions to ipsilesional M1 and secondary motor areas after stroke that are followed by time-dependent changes in neuronal connectivity during recovery. By using functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM), Schulz et al. investigated interactions between parietal cortices and frontal motor areas of the ipsilesional hemisphere in stroke patients as compared to healthy controls, as well as whether the degree of neuronal coupling correlates with residual functional deficit.

Fifteen patients (7 male, one left-handed, aged 68±8.5 years) were included roughly three months after first-ever ischemic stroke. Residual motor function was determined by a combination of grip force, the Nine-hole-peg test (NHP), and the Fugl-Meyer score for the upper extremity (UEFM). These assessments were compared to those of seventeen healthy controls of comparable age and sex (10 male, one left-handed, aged aged 64±9.9 years). Participants underwent event-related functional brain imaging while performing 30 isometric visually-guided whole hand grips with the paretic hand using a grip force response device. Controls were pseudo-randomly assigned to move either their right or left hand. All participants underwent functional imaging using a gradient echo-planar imaging sequence with a 3T MRI scanner. Image analysis was performed to identify areas of task-related brain activation for each patient, and these areas were quantified using blood oxygenation level dependent (BOLD) parameter estimates for five ipsilesional areas (M1, PMv, SMA, anterior (aIPS) and caudal part of the intraparietal sulcus (cIPS).

Dynamic causal modeling was utilized to analyze interregional connectivity using a priori assumptions. The coupling parameters were divided into three matrices. The A matrix represented the “resting state” of task-independent interregional coupling. The B matrix represented the changes in coupling parameters elicited by the task input, and the C matrix specified regions receiving exogenous inputs. Group-wise Bayesian model averaging was applied to derive mean coupling estimates for each connection weighted by the model probabilities. Two-tailed Wilcoxon rank sum exact tests were used to determine the significance of differences between stroke patients and controls. Spearman’s correlation coefficient was used to evaluate the relationship between coupling estimates and clinical scores.

In stroke patients, the task studied induced a significant increase in BOLD signal in the ipsilesional M1, PMv, SMA, aIPS, and cIPS both in the ipsilesional and contralesional hemispheres. Accounting for spatial variability in focal brain activation, it was found that both cases and controls had similar subject-specific peak coordinates and Euclidean distances between individual and group-level coordinates. The stroke patients and controls showed comparable grip-related effective connectivity values, with the most prominent increase in information flow being found from SMA to M1 and PMv to M1. Stroke patients also exhibited enhanced facilitatory connectivity from aIPS or M1 and M1 to aIPS (p<0.05). Interestingly, there were no significant correlations between clinical performance and coupling estimates.

This study extends previous findings suggesting that parietal brain region interactions with frontal motor areas may facilitate plastic changes after stroke. It is likely that posterior parietal brain regions act as important nodes for sensorimotor integration, particularly when visual rather proprioceptive feedback was given, as was the case in this study. The lack of association between coupling and residual motor function was unexpected. The authors posit that this may suggest that direct activity of the posterior parietal cortex may be more integrative, relying more on other parameters and less directly reflective of functional motor activity. The issue was also raised that current measures of dexterous hand function may not be adequate to assess minute, nuanced improvements, which has been an issue when relating clinical scoring to functional imaging in multiple areas of research. This study also has many of the other limitations when clinically correlating functional brain imaging data (i.e.. motor tasks not specifically designed to activate the area in question, possibility of “hidden” accessory pathways that were not directly studied, inability to control for differences in cognitive processing when performing task). Regardless, the study provides a valuable insight into the role of the ipsilesional parietofrontal motor network and its importance with respect to motor functioning and recovery after stroke.

The CARS Study: Encouraging Results for Stroke Recovery with Cerebrolysin

Ilana Spokoyny, MD

Muresanu DF, Heiss WD, Hoemberg V, Bajenaru O, Popescu CD, Vester JC et al. Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial. Stroke. 2016

The data on neuroprotectants has been quite discouraging so far. Often, an agent will prove effective at reducing stroke size or improving patient outcome in laboratory models of ischemia, but this effect does not always translate to clinical trials. The authors of the CARS study point out that this disconnect may be attributed to inappropriate animal models, and the simplistic design of human clinical trials which have not taken into account the complex parallel pathways which contribute to cerebral ischemia. Previous agents have targeted one pathophysiologic pathway, but the authors suggest that a multi-targeted therapy is necessary. Cerebrolysin, a porcine-derived neuropeptide combination, may in fact be an exception to the notion that neuroprotectants do not work, based on this phase II randomized controlled clinical trial conducted in Romania, Ukraine, and Poland.

Cerebrolysin has been previously shown to be effective in animal models, even when started up to 48 hours post-stroke. It has also been studied in several small clinical trials, and as a subgroup of a larger clinical trial, in which it was shown to improve outcome and reduce mortality after severe stroke. However, the effects did not persist over time, and had disappeared by day 90. In these previous trials, Cerebrolysin was given in the acute phase and for a short duration. The authors comment that the potential neurotrophic and neuroplastic effects may have been overlooked.

The CARS study compared arm motor recovery at 90 days among patients receiving Cerebrolysin or placebo. The trial included 205 patients between 18-80 years old, with supratentorial ischemic strokes at least 4 cc in volume, with baseline mRS 0-1, moderate or minimal aphasia, and minimal to severe arm weakness. The mean baseline NIHSS was 9.2. Patients were treated with IV Cerebrolysin or placebo daily for 21 days, beginning at 24-72 hours post-stroke. All patients also received early aggressive rehabilitation for 21 days, which was started within 72 hours of stroke onset and consisted of exercise 2 hours per day, five days per week. The patients then continued to exercise for 30 minutes per day, 3 days a week post-discharge.

The primary outcome was arm motor function, measured by the Action Research Arm Test score at 90 days. The ARAT score ranges from 0 (no function) to 57 (no limitation). Patients with post-stroke baseline score 0-50 were included. The primary outcome showed a large superiority of Cerebrolysin (increased ARAT in 92%, an average of 30.7 points) over placebo (increased ARAT in 84%, an average of 15.9 points). A good functional outcome (mRS 0-1) was seen in 42% of Cerebrolysin-treated patients compared with 15% of placebo-treated patients. The secondary outcome was a composite of twelve outcome scales, including gait velocity, fine motor function, ADL independence, aphasia, neglect, quality of life, cognition, and depression. The composite outcome showed a small superiority of Cerebrolysin. The safety of Cerebrolysin was equivalent to placebo. The most common adverse effects were UTI, depression, and cytolytic hepatitis in the Cerebrolysin group, and UTI, hypertension, and depression in the placebo group.

A larger-scale phase III randomized trial is needed to ensure that effects were not exaggerated by poor outcomes in the placebo group, small sample size, or the fact that both groups engaged in early and sustained rehabilitation therapy. However, this phase II trial is quite encouraging for the prospect of an effective neuroprotective and neuroplastic agent on the horizon.

Functional gain in stroke rehabilitation a predictor of long-term mortality

Peggy Nguyen, MD

Scrutinio D, Monitillo V, Guida P, Nardulli R, Multari V, Monitillo F, et al. Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on Long-Term Survival. Stroke. 2015

A common scenario vascular neurologists encounter are patients who ask us questions that run the gamut of: What’s going to happen after I leave the hospital or after I leave rehabilitation? The world of stroke has recently been focused on acute interventions at presentation and predictors of outcome acutely, but long-term, what are some of the things we can advise our patients? Here, the authors performed a cross-section study evaluating the association of stroke rehabilitation, as measured by improvement in functional independence motor (FIM) score on admission and discharge, with long-term mortality, as well as predictors of successful stroke rehabilitation.

1010 consecutive patients admitted for stroke rehabilitation with an FIM score < 80 and a recent (< 90 day from onset) ischemic or hemorrhagic stroke were enrolled in the study. Variables identified as independent positive correlates of FIM gain were younger age, being married, lower NIHSS score at time of rehabilitation admission, decreased time from stroke onset to rehabilitation admission, and presence of aphasia. Over a median follow up of 6.17 years, 36.9% of the subjects died. Age, coronary heart disease, atrial fibrillation, total cholesterol, and FIM gain were found to be independently associated with mortality. After adjusting for mortality risk markers, FIM gain remained a predictor of long-term mortality risk.  

These study yielded some interesting results. The finding that FIM gain is a predictor of long-term mortality suggests that better functional improvement with rehabilitation decreases long-term mortality risk in stroke survivors. Of course, as the authors also point out, this association may also be confounded by the finding that younger age and lower NIHSS were associated with higher FIM gain; therefore, mortality may be a reflection of severity of stroke in an older population rather than rehabilitation, but this may still be helpful in how we counsel our patients as we transition them to rehabilitation. In addition, the finding that a higher FIM gain is associated with less time between stroke onset to rehabilitation is highly relevant and, again, not only helps us when counseling patients and their families, but may also aid in decision making at discharge.

By |October 16th, 2015|rehabilitation|1 Comment

Neuromuscular Electrical Stimulation for Post-Stroke Spasticity

Rizwan Kalani, MD  

Stein C, Fritsch CG, Robinson C, Sbruzzi G, and Méa Plentz RD. Effects of Electrical Stimulation in Spastic Muscles After Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Stroke. 2015

Spasticity occurs in 20-30% of individuals with prior stroke. Common management strategies include administration of GABAergic agents (baclofen), ankle-foot orthotics, physical therapy, and tendon surgeries. Given inconsistent results from prior randomized controlled trials (RCTs), Stein et al did a systematic review and meta-analysis of studies evaluating the effect of neuromuscular electrical stimulation (NMES) on post-stroke spasticity.

The authors reviewed the literature for RCTs that assessed the effect of NMES (with or without additional therapeutic intervention) for spasticity after stroke. Studies evaluating at least three days of NMES, regardless of dosage, and applied to the upper or lower extremities, were included. Two independent reviewers selected the studies, extracted relevant data, and assessed for risk of bias. The primary outcome was spasticity (per the modified ashworth scale) and secondary outcome was range of motion (ROM) (by goniometer).

Of the 29 RCTs (with 940 subjects) that met the inclusion criteria for the systematic review, 14 were included in the meta-analysis (the other 15 had missing data and used other scales to assess spasticity). Most studies used NMES frequencies of 18-50 Hz and pulse duration from 0.1-0.3 seconds. NMES (alone or combined with other treatment) was associated with reduction in spasticity (-0.30, 95% CI: -0.58 – -0.03) compared to the control group. The 12 studies that combined NMES with another therapeutic modality for spasticity significantly reduced spasticity (-0.35, 95% CI: -0.63 – -0.07) whereas the two studies that evaluated NMES alone did not. Interestingly, reports that used NMES on the legs showed a significant reduction in spasticity (-0.78, 95% CI: -1.02 – -0.54) but those with NMES applied to the upper extremity did not. NMES (alone or with other intervention) was associated with an increase in ROM (2.87, 95% CI: 1.18-4.56). Again, when NMES was combined another modality, a significant increase in ROM was noted (2.73, 95% CI: 1.07-4.39); this did not hold true when NMES was used alone. Application to the leg and elbow improved ROM, whereas use on the wrist did not.

NMES combined with other therapeutic interventions improves spasticity and increases ROM after stroke. RCTs evaluated varied in the time the intervention was started after stroke, treatment duration, stimulation parameters used, degree of spasticity and functional deficit, as well as comparative treatments evaluated in certain studies; these factors may affect response to NMES. Establishing efficacy would be best assessed by a large, high-quality RCT. However, based on this analysis, it is worth considering this option in conjunction with a physiatrist and the patient.