Richard F. Macko

Fatigue after stroke: Relationship to mobility, fitness, ambulatory activity, social support, and falls efficacy

&NA; Fatigue is common and persistent in stroke survivors, yet it is not known how mobility deficits, fitness, or other factors, such as social support, relate to fatigue severity, or whether subjective fatigue contributes to reduced ambulatory activity. The severity of fatigue in a sample of 53 community‐dwelling subjects with chronic hemiparetic stroke was examined, and relationships among fatigue and mobility deficit severity, cardiovascular‐metabolic fitness, ambulatory activity, social support, and self‐efficacy for falls were identified. Measures included the Fatigue Severity Scale, timed 10‐meter walks, the Berg Balance Scale, submaximal and peak VO2, total daily step activity derived from microprocessor‐linked Step Activity Monitors, the Medical Outcomes Study Social Support Survey, and the Falls Efficacy Scale. Forty‐six percent of the sample had severe fatigue. Fatigue showed no relationship to ambulatory activity. Fatigue severity was associated with the Berg Balance Scale (p > .01) and falls efficacy (p > .01), but not with cardiovascular fitness variables. Patients with elevated fatigue severity scores had lower social support (p > .05) and poorer falls efficacy scores (p > .05) than patients reporting less fatigue. Only falls efficacy was predictive of fatigue severity (r2 = 0.216, p > .01). Further studies are needed to evaluate whether rehabilitation strategies that include not only fitness and mobility interventions, but also social/behavioral and self‐efficacy components, are associated with reduced fatigue and increased ambulation.

Muscle molecular phenotype after stroke is associated with gait speed

The disability of patients after stroke is generally attributed to upper motor neuron defects, but secondary changes in paretic muscle may enhance the disability. We analyzed the molecular phenotype and metabolic profile of the paretic and nonparetic vastus lateralis (VL) and we measured the severity of gait deficit in 13 patients at least 6 months after ischemic stroke. The results showed a significant increase in the proportion of fast myosin heavy chain (MHC, 68 ± 14%) in the paretic compared to the nonparetic VL (50 ± 13%). The specific activity of citrate synthase and glyceraldehyde phosphodehydrogenase was not significantly different between the two sides. The proportion of fast MHC was inversely associated with severity of gait deficit indexed by self‐selected walking speed in the paretic leg, but not the nonparetic leg. Our findings demonstrate significant and potentially modifiable secondary biologic changes in hemiparetic muscle phenotype that may contribute to the disability of stroke. Muscle Nerve 30: 209–215, 2004

High prevalence of abnormal glucose metabolism and poor sensitivity of fasting plasma glucose in the chronic phase of stroke.

Background: Cardiovascular disease is the leading cause of death in long-term stroke survivors, and whole-body glucose metabolism is strongly linked to cardiovascular disease risk. This study provides important preliminary information on the prevalence of abnormal glucose metabolism in chronic stroke patients (mean 3 years after stroke) and reports on the utility of screening for abnormalities using fasting plasma glucose (FPG) in this population. Methods: Two hundred and sixteen chronic hemiparetic stroke patients were screened for diabetes status by medical history and FPG. A subset (n = 80) was evaluated by oral glucose tolerance test to assess the utility of screening for abnormalities using FPG alone. Results: Seventy-five of the 216 (35%) had type 2 diabetes by medical history. Another 70 were either diabetic (n = 11) or had impaired fasting glucose (n = 59) based on a single blood draw at the time of screening. FPG among non-diabetic stroke patients had a sensitivity of 49% for predicting abnormalities in the 2-hour glucose level during oral glucose tolerance test. Cumulative results identify 77% as abnormal (impaired or diabetic) on the basis of medical history, fasting plasma glucose, and/or 2-hour glucose level. Conclusions: The prevalence of abnormal glucose metabolism is extremely high in chronic stroke and is underestimated on the basis of FPG.

Progressive adaptive physical activity in stroke improves balance, gait, and fitness: preliminary results.

Abstract Purpose: We conducted a noncontrolled pilot intervention study in stroke survivors to examine the efficacy of lowintensity adaptive physical activity to increase balance, improve walking function, and increase cardiovascular fitness and to determine whether improvements were carried over into activity profiles in home and community. Method: Adaptive physical activity sessions were conducted 3 times/week for 6 months. The main outcomes were Berg Balance Scale, Dynamic Gait Index, 6-Minute Walk Test, cardiovascular fitness (VO2 peak), Falls Efficacy Scale, and 5-day Step Activity Monitoring. Results: Seven men and women with chronic ischemic stroke completed the 6-month intervention. The mean Berg Balance baseline score increased from 33.9 ± 8.5 to 46 ± 6.7 at 6 months (mean ± SD; p = .006). Dynamic Gait Index increased from 13.7 ± 3.0 to 19.0 ± 3.5 (p = .01). Six-minute walk distance increased from 840 ± 110 feet to 935 ± 101 feet (p = 0.02). VO2 peak increased from 15.3 ± 4.1 mL/kg/min to 17.5 ± 4.7 mL/kg/min (p = .03). There were no significant changes in falls efficacy or free-living ambulatory activity. Conclusion: A structured adaptive physical activity produces improvements in balance, gait, fitness, and ambulatory performance but not in falls efficacy or free-living daily step activity. Randomized studies are needed to determine the cardiovascular health and functional benefits of structured group physical activity programs and to develop behavioral interventions that promote increased free-living physical activity patterns.

Role of walking-exercise therapy after stroke

Stroke commonly leads to reduced mobility, which leads to deconditioning and a worsening of vascular risk factors, such as diabetes. The worsened risk profile leads to further strokes and disability – a vicious cycle for the stroke survivor. Exercise (walking) therapy may break this cycle by providing adequate stimuli for improving gait through plastic adaptation in the brain and through increasing fitness. Randomized, controlled data demonstrate the efficacy for gains in fitness and walking speed, the latter being related to lasting changes in activation patterns of the brainstem and cerebellum. Diabetes and muscle inflammation can also be improved by aerobic exercise training. The scope of this review summarizes these data and identifies unresolved issues related to optimization, intensity and maintenance of therapy effects. Exercise should be an integral part of every rehabilitation program.

Exercise Intervention Research in Stroke: Optimizing Outcomes Through Treatment Fidelity

Abstract Background: Demonstrating the treatment fidelity of an intervention is a key methodological requirement of any trial testing the impact of the intervention. Purpose: The purpose of this report was to serve as a model for evaluating treatment fidelity in stroke exercise intervention studies and to provide evidence for treatment fidelity in the Exercise Training for Hemiparetic Stroke Intervention Development Study. Methods: Treatment fidelity was evaluated based on study design, training of interventionists, and delivery and receipt of the intervention. Results: There were some concerns about design fidelity as the control group and intervention group traveled to the study location together and received different exercise programs in the same facility. With regard to training of interventionists, observations were utilized to help maintain adherence to the protocol. There was strong support for the delivery and receipt of the intervention with participants exposed to the anticipated number of exercise sessions. As per study protocol, there was evidence that progress toward the proposed physical activity goal was made. Treatment fidelity findings are reported using cumulative data rather than at points throughout the study. Thus the findings may be conservative with regard adherence, for example, to time spent in exercise. Conclusion: In addition to assurance of true testing of the intervention in this study, treatment fidelity of this work provides a useful model for replication and critically important information to better understand the type, dose, and length of exposure to exercise interventions that is needed to optimize stroke recovery.

Reduced thrombomodulin in human peripheral nerve microvasculature

Thrombomodulin (TM), a vascular endothelial receptor, terminates the actions of thrombin and accelerates activated protein C formation. TM is ubiquitous throughout the systemic microcirculation but is reduced in brain regions predisposed to lacunar infarction. We investigated whether TM is present within human nerve and differentially expressed according to vessel caliber and proximity to the blood–nerve barrier. Vascular endothelial TM was detected on sural nerve biopsies with immunohistochemistry. The proportion of TM‐positive microvessels was expressed relative to total von Willebrand factor (vWF)–positive vessels. Although vWF was detectable in all microvessels, TM expression was absent from the perineurial vessels. TM was detected in 47% (15–80%, 95% confidence level) of larger epineurial arterioles, in 43% (30–61%) of smaller epineurial vessels, and in 30% (19–47%) of endoneurial vessels. These findings demonstrate that TM is present in human nerve microvasculature but is regionally deficient in proximity to the blood–nerve barrier, which may predispose nerve to microvascular ischemia in inflammatory/prothrombotic conditions.