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Purpose: This systematic umbrella review examines and updates the evidence on the relationship between physical activity (PA) and blood pressure (BP) presented in the 2008 Physical Activity Guidelines Advisory Committee Scientific Report., Methods: We performed a systematic review to identify systematic reviews and meta-analyses involving adults with normal BP, prehypertension, and hypertension published from 2006 to February 2018., Results: In total, 17 meta-analyses and one systematic review with 594,129 adults ≥18 yr qualified. Strong evidence demonstrates: 1) an inverse dose-response relationship between PA and incident hypertension among adults with normal BP; 2) PA reduces the risk of cardiovascular disease (CVD) progression among adults with hypertension; 3) PA reduces BP among adults with normal BP, prehypertension, and hypertension; and 4) the magnitude of the BP response to PA varies by resting BP, with greater benefits among adults with prehypertension than normal BP. Moderate evidence indicates the relationship between resting BP and the magnitude of benefit does not vary by PA type among adults with normal BP, prehypertension, and hypertension. Limited evidence suggests the magnitude of the BP response to PA varies by resting BP among adults with hypertension. Insufficient evidence is available to determine if factors such as sex, age, race/ethnicity, socioeconomic status, and weight status or the frequency, intensity, time, and duration of PA influence the associations between PA and BP., Conclusions: Future research is needed that adheres to standard BP measurement protocols and classification schemes to better understand the influence of PA on the risk of comorbid conditions, health-related quality of life, and CVD progression and mortality; the interactive effects between PA and antihypertensive medication use; and the immediate BP-lowering benefits of PA.

Objective: To assess the effectiveness of robotically assisted body weight supported treadmill training (RABWSTT) for improving cardiovascular fitness in chronic motor incomplete spinal cord injury (CMISCI)., Design: Pilot prospective randomized, controlled clinical trial., Setting: Outpatient rehabilitation specialty hospital., Participants: Eighteen individuals with CMISCI with American Spinal Injury Association (ASIA) level between C4 and L2 and at least one-year post injury. Interventions CMISCI participants were randomized to RABWSTT or a home stretching program (HSP) three times per week for three months. Those in the home stretching group were crossed over to three months of RABWSTT following completion of the initial three month phase., Outcome Measures: Peak oxygen consumption (peak VO(2)) was measured during both robotic treadmill walking and arm cycle ergometry: twice at baseline, once at six weeks (mid-training) and twice at three months (post-training). Peak VO(2) values were normalized for body mass., Results: The RABWSTT group improved peak VO(2) by 12.3% during robotic treadmill walking (20.2 ± 7.4 to 22.7 ± 7.5 ml/kg/min, P = 0.018), compared to a non-significant 3.9% within group change observed in HSP controls (P = 0.37). Neither group displayed a significant change in peak VO2 during arm cycle ergometry (RABWSTT, 8.5% (P = 0.25); HSP, 1.76% (P = 0.72)). A repeated measures analysis showed statistically significant differences between treatments for peak VO(2) during both robotic treadmill walking (P = 0.002) and arm cycle ergometry (P = 0.001)., Conclusion: RABWSTT is an effective intervention model for improving peak fitness levels assessed during robotic treadmill walking in persons with CMISCI.

Background: Peak aerobic capacity (VO2 peak) is severely worsened after disabling stroke, having serious implications for function, metabolism, and ongoing cardiovascular risk. Work from our laboratory and others has previously shown that modest improvements in VO2 peak are possible in stroke participants with aerobic exercise training. The purpose of the current investigation was to test the extent to which greater enhancements in VO2 peak after stroke are possible using a treadmill protocol with far greater emphasis on intensity progression compared with a protocol without such emphasis., Methods: Using a randomized design, we compared stroke survivors engaged in higher intensity treadmill training (HI-TM, 80% heart rate reserve [HRR]) with those undergoing lower intensity treadmill training (LO-TM, 50% HRR). Measured outcomes were change in VO2 peak, 6-minute walk distance (6MWD), 30-ft walk times (30WT), and 48-hour step counts (48SC). LO-TM participants trained for a longer period of time per session in an effort to approximately match workload/caloric expenditure. Participants were randomized with stratification according to age and baseline walking capacity., Results: HI-TM participants (n = 18) had significantly greater gains in VO2 peak (+34%) than LO-TM participants (n = 16; +5%) across the 6-month intervention period (P = .001, group × time interaction). Conversely, there was no statistical difference between groups in the changes observed for 6MWD, 30WT, or 48SC., Conclusions: HI-TM is far more effective than LO-TM for improving VO2 peak after disabling stroke. The magnitude of relative improvement for HI-TM was double compared with previous reports from our laboratory with probable clinical significance for this population., (Published by Elsevier Inc.)

Purpose: This scientific statement provides an overview of the evidence on physical activity and exercise recommendations for stroke survivors. Evidence suggests that stroke survivors experience physical deconditioning and lead sedentary lifestyles. Therefore, this updated scientific statement serves as an overall guide for practitioners to gain a better understanding of the benefits of physical activity and recommendations for prescribing exercise for stroke survivors across all stages of recovery., Methods: Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and the American Heart Association's Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and indicate gaps in current knowledge., Results: Physical inactivity after stroke is highly prevalent. The assessed body of evidence clearly supports the use of exercise training (both aerobic and strength training) for stroke survivors. Exercise training improves functional capacity, the ability to perform activities of daily living, and quality of life, and it reduces the risk for subsequent cardiovascular events. Physical activity goals and exercise prescription for stroke survivors need to be customized for the individual to maximize long-term adherence., Conclusions: The recommendation from this writing group is that physical activity and exercise prescription should be incorporated into the management of stroke survivors. The promotion of physical activity in stroke survivors should emphasize low- to moderate-intensity aerobic activity, muscle-strengthening activity, reduction of sedentary behavior, and risk management for secondary prevention of stroke., (© 2014 American Heart Association, Inc.)

Robotics is rapidly emerging as a viable approach to enhance motor recovery after disabling stroke. Current principles of cognitive motor learning recognize a positive relationship between reward and motor learning. Yet no prior studies have established explicitly whether reward improves the rate or efficacy of robotics-assisted rehabilitation or produces neurophysiologic adaptations associated with motor learning. We conducted a 3 wk, 9-session clinical pilot with 10 people with chronic hemiparetic stroke, randomly assigned to train with an impedance-controlled ankle robot (anklebot) under either high reward (HR) or low reward conditions. The 1 h training sessions entailed playing a seated video game by moving the paretic ankle to hit moving onscreen targets with the anklebot only providing assistance as needed. Assessments included paretic ankle motor control, learning curves, electroencephalograpy (EEG) coherence and spectral power during unassisted trials, and gait function. While both groups exhibited changes in EEG, the HR group had faster learning curves (p = 0.05), smoother movements (p

Background and Objective: Ambulatory subjects after stroke may benefit from gait-oriented cardiovascular fitness training, but trials to date have not primarily assessed older persons., Methods: Thirty-eight subjects (age >60 years) with residual hemiparetic gait were enrolled >6 months after stroke. Participants were randomized to receive 3 months (3×/week) progressive graded, high-intensity aerobic treadmill exercise (TAEX) or conventional care physiotherapy. Primary outcome measures were peak exercise capacity (Vo(2peak)) and sustained walking capacity in 6-minute walks (6MW). Secondary measures were gait velocity in 10-m walks, Berg Balance Scale, functional leg strength (5 chair-rise), self-rated mobility (Rivermead Mobility Index), and quality of life (SF-12)., Results: Thirty-six participants completed the study (18 TAEX, 18 controls). TAEX but not conventional care improved Vo(2peak) (difference 6.4 mL/kg/min, P < .001) and 6MW (53 m, P < .001). Likewise, maximum walking speed (0.13 m/s, P = .01), balance (P < .05), and the mental subscore of the SF-12 (P < .01) improved more after TAEX. Gains in Vo(2peak) correlated with the degree at which training intensity could be progressed in the individual participant (P < .01). Better walking was related to progression in treadmill velocity and training duration (P < .001). Vo(2peak) and 6MW performances were still higher 1 year after the end of training when compared with the baseline, although endurance walking (6MW) at 1 year was lower than immediately after training (P < .01)., Conclusion: This trial demonstrates that TAEX effectively improves cardiovascular fitness and gait in persons with chronic stroke.

Background and Purpose: Animal studies provide strong evidence that aerobic exercise training positively influences cerebral blood flow, but no human studies support the use of exercise for improving cerebral hemodynamics. This randomized study in stroke survivors assessed the effects of treadmill aerobic exercise training (TM) on cerebral blood flow parameters compared to a control intervention of nonaerobic stretching., Methods: Thirty-eight participants (19 in TM group and 19 in control group) with remote stroke (>6 months) and mild to moderate gait deficits completed middle cerebral artery blood flow velocity measurements by transcranial Doppler ultrasonography before and after a 6-month intervention period. Middle cerebral artery blood flow velocity was assessed bilaterally during normocapnia and hypercapnia (6% CO2). Cerebral vasomotor reactivity (cVMR) was calculated as percent change in middle cerebral artery blood flow velocity from normocapnia to hypercapnia (cVMR percent) and as an index correcting percent change for absolute increase in end tidal CO2 (cVMR index)., Results: The TM group had significantly larger improvements than did controls for both ipsilesional and contralesional cVMR index (P≤0.05) and contralesional cVMR percent (P≤0.01). Statin users in the TM group (n=10) had higher baseline cVMR and lower training-induced cVMR change, indicating that cVMR change among those not using statins (n=9) primarily accounted for the between-group effects. There was a 19% increase in Vo2 peak for the TM group compared to a 4% decrease in the control group (P<0.01), and peak fitness change correlated with cVMR change (r=0.55; P<0.05)., Conclusions: Our data provide the first evidence to our knowledge of exercise-induced cVMR improvements in stroke survivors, implying a protective mechanism against recurrent stroke and other brain-related disorders. Statin use appears to regulate cVMR and the cVMR training response.

Background and Purpose: This randomized controlled trial tests the efficacy of bilateral arm training with rhythmic auditory cueing (BATRAC) versus dose-matched therapeutic exercises (DMTEs) on upper-extremity (UE) function in stroke survivors and uses functional magnetic resonance imaging (fMRI) to examine effects on cortical reorganization., Methods: A total of 111 adults with chronic UE paresis were randomized to 6 weeks (3×/week) of BATRAC or DMTE. Primary end points of UE assessments of Fugl-Meyer UE Test (FM) and modified Wolf Motor Function Test Time (WT) were performed 6 weeks prior to and at baseline, after training, and 4 months later. Pretraining and posttraining, fMRI for UE movement was evaluated in 17 BATRAC and 21 DMTE participants., Results: The improvements in UE function (BATRAC: FM Δ = 1.1 + 0.5, P = .03; WT Δ = -2.6 + 0.8, P < .00; DMTE: FM Δ = 1.9 + 0.4, P < .00; WT Δ = -1.6 + 0.7; P = .04) were comparable between groups and retained after 4 months. Satisfaction was higher after BATRAC than DMTE (P = .003). BATRAC led to significantly higher increase in activation in ipsilesional precentral, anterior cingulate and postcentral gyri, and supplementary motor area and contralesional superior frontal gyrus (P < .05). Activation change in the latter was correlated with improvement in the WMFT (P = .01)., Conclusions: BATRAC is not superior to DMTE, but both rehabilitation programs durably improve motor function for individuals with chronic UE hemiparesis and with varied deficit severity. Adaptations in brain activation are greater after BATRAC than DMTE, suggesting that given similar benefits to motor function, these therapies operate through different mechanisms.

Background and Purpose: Resting and reactive hyperemic leg blood flows are significantly reduced in the paretic compared with the nonparetic limb after disabling stroke. Our objective was to compare the effects of regular treadmill exercise (TM) with an active control regimen of supervised stretching (CONTROL) on peripheral hemodynamic function., Methods: This intervention study used a randomized, controlled design, in which participants were randomized with stratification according to age and baseline walking capacity to ensure approximate balance between the 2 groups. Fifty-three chronic, ischemic stroke participants (29 TM and 24 CONTROL) with mild to moderate hemiparetic gait completed bilateral measurements of lower leg resting and reactive hyperemic blood flow using venous occlusion strain gauge plethysmography before and after the 6-month intervention period. Participants also underwent testing to track changes in peak aerobic fitness across time., Results: Resting and reactive hyperemic blood flows were significantly reduced in the paretic compared with the nonparetic limb at baseline before any intervention (-28% and -34%, respectively, P<0.01). TM increased both resting and reactive hyperemic blood flow in the paretic limb by 25% compared with decreases in CONTROL (P<0.001, between groups). Similarly, nonparetic leg blood flow was significantly improved with TM compared with controls (P<0.001). Peak aerobic fitness improved by 18% in TM and decreased by 4% in CONTROL (P<0.01, between groups), and there was a significant relationship between blood flow change and peak fitness change for the group as a whole (r=.30, P<0.05)., Conclusions: Peripheral hemodynamic function improves with regular aerobic exercise training after disabling stroke.

Background: Aerobic treadmill exercise (T-EX) therapy has been shown to benefit walking and cardiorespiratory fitness in stroke survivors with chronic gait impairment even long after their stroke. The response, however, varies between individuals., Objective: The purpose of this post hoc analysis of 2 randomized controlled T-EX trials was to identify predictors for therapy response., Methods: In all, 52 participants received T-EX for 3 (Germany) or 6 (United States) months. Improvements in overground walking velocity (10 m/6-min walk) and fitness (peak VO(2)) were indicators of therapy response. Lesion location and volume were measured on T1-weighted magnetic resonance scans., Results: T-EX significantly improved gait and fitness, with gains in 10-m walk tests ranging between +113% and -25% and peak VO(2) between -12% and 88%. Baseline walking impairments or fitness deficits were not predictive of therapy response; 10-m walk velocity improved more in those with subcortical rather than cortical lesions and in patients with smaller lesions. Improvements in 6-minute walk velocity were greater in those with more recent strokes and left-sided lesions. No variable other than training intensity, which was different between trials, predicted fitness gains., Conclusions: Despite proving overall effectiveness, the response to T-EX varies markedly between individuals. Whereas intensity of aerobic training seems to be an important predictor of gains in cardiovascular fitness, lesion size and location as well as interval between stroke onset and therapy delivery likely affect therapy response. These findings may be used to guide the timing of training and identify subgroups of patients for whom training modalities could be optimized.

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.

Purpose: We conducted a non-controlled pilot intervention study in stroke survivors to examine the efficacy of low-intensity 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.

Background and Purpose: Stroke often impairs gait thereby reducing mobility and fitness and promoting chronic disability. Gait is a complex sensorimotor function controlled by integrated cortical, subcortical, and spinal networks. The mechanisms of gait recovery after stroke are not well understood. This study examines the hypothesis that progressive task-repetitive treadmill exercise (T-EX) improves fitness and gait function in subjects with chronic hemiparetic stroke by inducing adaptations in the brain (plasticity)., Methods: A randomized controlled trial determined the effects of 6-month T-EX (n=37) versus comparable duration stretching (CON, n=34) on walking, aerobic fitness and in a subset (n=15/17) on brain activation measured by functional MRI., Results: T-EX significantly improved treadmill-walking velocity by 51% and cardiovascular fitness by 18% (11% and -3% for CON, respectively; P<0.05). T-EX but not CON affected brain activation during paretic, but not during nonparetic limb movement, showing 72% increased activation in posterior cerebellar lobe and 18% in midbrain (P<0.005). Exercise-mediated improvements in walking velocity correlated with increased activation in cerebellum and midbrain., Conclusions: T-EX improves walking, fitness and recruits cerebellum-midbrain circuits, likely reflecting neural network plasticity. This neural recruitment is associated with better walking. These findings demonstrate the effectiveness of T-EX rehabilitation in promoting gait recovery of stroke survivors with long-term mobility impairment and provide evidence of neuroplastic mechanisms that could lead to further refinements in these paradigms to improve functional outcomes.

Purpose: The purpose of this qualitative study was to explore factors that motivated older adults with ischemic stroke to engage in a task-oriented treadmill aerobic exercise (T-AEX) intervention study., Method: Participants included community-dwelling individuals post stroke with mild-to-moderate hemiparetic gait deficits who completed a 6-month T-AEX study. A total of 29 participants attended focus groups or individual telephone interviews., Results: Thirty-nine codes were identified and were reduced to 8 themes: personal goals supported by 7 codes, psychological benefits supported by 8 codes, physical benefits supported by 10 codes, research-associated supervised treadmill exercise benefits supported by 5 codes, objective and verbal encouragement received supported by 4 codes, social support related to exercise supported by 2 codes, improvement in instrumental activities of daily living supported by 2 codes, and self-determination supported by 1 code. All themes reflected factors that influenced subjects' willingness to participate in the study and adhere to the exercise intervention. Of the themes identified, personal goals, physical benefits, and psychological benefits occurred most frequently., Conclusion: This qualitative study provides information that may be used to enhance motivation to exercise in individuals with stroke and promote carryover and integration of exercise behaviors into everyday life.

The effects of task-repetitive locomotor training on stroke patients' spatial and temporal gait parameters during unassisted walking are not well understood. This study determined the effects of treadmill aerobic exercise (T-EX) on spatial and temporal gait parameters that underlie changes in overground walking function. Thirty-nine subjects with hemiparetic stroke underwent T-EX three times weekly for 6 months. We measured the subjects pre- and posttraining on 30-foot timed walks and 6-minute distance walks with usual assistive devices and on an 8 m instrumented walkway without assistive devices. T-EX improved 30-foot walks by 17% and 6-minute walks by 23%. Unassisted walking velocity increased 22%, stride length increased 13%, and cadence increased 7%. Paretic and nonparetic step lengths increased significantly, and respective step times decreased significantly. Interlimb symmetry did not change. This study presents preliminary evidence that changes in spatial and temporal gait parameters contribute to the increased velocity of subjects with stroke after T-EX.

Stroke is the leading cause of disability in the United States. New evidence reveals significant structural and metabolic changes in skeletal muscle after stroke. Muscle alterations include gross atrophy and shift to fast myosin heavy chain in the hemiparetic (contralateral) leg muscle; both are related to gait deficit severity. The underlying molecular mechanisms of this atrophy and muscle phenotype shift are not known. Inflammatory markers are also present in contralateral leg muscle after stroke. Individuals with stroke have a high prevalence of insulin resistance and diabetes. Skeletal muscle is a major site for insulin-glucose metabolism. Increasing evidence suggests that inflammatory pathway activation and oxidative injury could lead to wasting, altered function, and impaired insulin action in skeletal muscle. The health benefits of exercise in disabled populations have now been recognized. Aerobic exercise improves fitness, strength, and ambulatory performance in subjects with chronic stroke. Therapeutic exercise may modify or reverse skeletal muscle abnormalities.

Patients with stroke are severely deconditioned, leading to metabolic abnormalities that significantly increase risk for myocardial infarction and recurrent stroke. This review characterizes the nature of the metabolic decline, the underlying causes, and the potential for progressive aerobic exercise to address metabolic impairment following disabling stroke. Although exercise training has previously been shown to improve peak aerobic capacity and sensorimotor function after stroke, establishing safe and effective exercise programs in this population presents unique challenges stemming from neurological deficit complexities and comorbid conditions. Thus, recommendations for application to practice are provided that include proper preexercise evaluation, guidelines for symptom-limited maximal effort exercise testing, as well as evidence-based suggestions for initiation and progression of an exercise program. Implementing regular, progressive exercise therapy is critical on the basis of the devastating impact of physical inactivity on overall metabolic heath. Prevalence of impaired or diabetic glucose metabolism may be as high as 80% in chronic stroke, predicting 2- and 3-fold increased risk for recurrent stroke, respectively. Tragically, nearly one third of patients with stroke experience recurrent stroke within 5 years, and comorbid cardiovascular conditions represent the leading cause of death in this population. Recent evidence showing the positive impact of exercise training on hyperinsulinemia and glucose tolerance in survivors of stroke is presented, given the central importance of these factors to overall cardiovascular risk. On the basis of these and other findings, structured exercise programs should be considered for all survivors of stroke.

Patients with stroke have elevated hemiparetic gait costs secondary to low activity levels and are often severely deconditioned. Decrements in peak aerobic capacity affect functional ability and cardiovascular-metabolic health and may be partially mediated by molecular changes in hemiparetic skeletal muscle. Conventional rehabilitation is time delimited in the subacute stroke phase and does not provide adequate aerobic intensity to reverse the profound detriments to fitness and function that result from stroke. Hence, we have studied progressive full body weight-support treadmill (TM) training as an adjunct therapy in the chronic stroke phase. Task-oriented TM training has produced measurable changes in fitness, function, and indices of cardiovascular-metabolic health after stroke, but the precise mechanisms for these changes remain under investigation. Further, the optimal dose of this therapy has yet to be identified for individuals with stroke and may vary as a function of deficit severity and outcome goals. This article summarizes the functional and metabolic decline caused by inactivity after stroke and provides current evidence that supports the use of TM training during the chronic stroke phase, with protocols and inclusion/exclusion criteria described. Our research findings are discussed in relation to associated research.

This pilot study evaluated the safety and feasibility of a 3-month progressive treadmill aerobic exercise (TM-AEX) program for persons with Parkinson disease with gait impairment. Eight subjects underwent a treadmill stress test to determine eligibility. Of these subjects, three were referred for further cardiac evaluation and five were enrolled. In 136 TM-AEX sessions, 11 falls or near falls and 9 episodes (8 asymptomatic) of systolic blood pressure drops >20 mmHg occurred. Harness supports prevented injury from falls. TM-AEX significantly improved the subjects' total Unified Parkinson's Disease Rating Scale scores and peak ambulatory workload capacities. This study suggests that an aerobic exercise program is feasible for persons who have Parkinson disease with gait impairment; however, precautions must be taken to prevent falls. Systolic blood pressure instability during exercise points to the need for autonomic dysfunction monitoring. Our data indicate that TM-AEX may reduce symptom severity and improve fitness. Further studies are needed for a better understanding of the risks and benefits of TM-AEX in this population.

Stroke is a leading cause of disability that results not only in persistent neurological deficits, but also profound physical deconditioning that propagates disability and worsens cardiovascular risk. The potential for exercise-mediated adaptations to improve function, fitness, and cardiovascular health after stroke has been underestimated: it represents an emerging arena in neurotherapeutics. To define the health rationale for cardiovascular (aerobic) exercise, we first outline the impact of debilitating secondary biological changes in muscle and body composition on fitness and metabolic health after stroke. We provide an overview of evidence-based advances in exercise therapeutics, with a focus on task-oriented models that combine a progressive aerobic conditioning stimulus with motor learning to improve multiple physiological domains that determine longitudinal outcomes after stroke. Although progress in development of safe and effective exercise strategies is advancing, fundamental questions regarding dose intensity, prescription to optimize central and peripheral neuromuscular adaptations, and the public health value of exercise in secondary stroke prevention remain unanswered. Key issues steering future research in exercise neurotherapeutics are discussed within the context of initiatives to facilitate translation to community-based studies, requisite for dissemination.

Stroke is the leading cause of disability in older Americans. Each year 750,000 Americans suffer a stroke, two thirds of whom are left with neurological deficits that persistently impair function. Principal among them is hemiparetic gait that limits mobility and increases fall risk, promoting a sedentary lifestyle. These events propagate disability by physical deconditioning and "learned non-use," with further functional declines accelerated by the sarcopenia and fitness decrements of advancing age. Conventional rehabilitation care typically provides little or no structured therapeutic exercise beyond the subacute stroke recovery period, based on natural history studies showing little or no further functional motor recovery beyond 6 months after stroke. Emerging evidence suggests that new models of task-oriented exercise have the potential to improve motor function even years after stroke. This article presents treadmill as a task-oriented training paradigm to optimize locomotor relearning while eliciting cardiovascular conditioning in chronic stroke patients. Protocols for exercise testing and longitudinal aerobic training progression are presented that provide fundamental formulas that safely approach the complex task of customizing aerobic training to gait deficit severity in the high CVD risk stroke population. The beneficial effects of 6 months task-oriented treadmill exercise on cardiovascular-metabolic fitness, energy cost of hemiparetic gait, ADL mobility task performance, and leg strength are discussed with respect to the central and peripheral neuromuscular adaptations targeted by the training. Collectively, these findings constitute one initial experience in a much broader neuroscience and exercise rehabilitation development of task-oriented training paradigms that offer a multisystems approach to improving both neurological and cardiovascular health outcomes in the chronic stroke population.

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 (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity 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%, delta% 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.

Purpose: Acute clinical events resulting from atherosclerosis (myocardial infarction, stroke) are associated with impaired endogenous fibrinolysis, the system by which the body lyses inappropriately formed thrombus. Endurance exercise training improves fibrinolysis in normal subjects and those with coronary artery disease. The hypothesis of this study was that exercise training would improve fibrinolysis in subjects with peripheral arterial disease (PAD)., Methods and Results: Twenty-one men with intermittent claudication (IC-EX) underwent treadmill exercise training for 6 months. Twenty age-matched male subjects with IC were followed for the same period (IC-NONEX). Fibrinolytic activity was measured prior to entry into exercise or "usual care," and at the completion of the study period. Fibrinolysis was quantified by measurement of the activity levels of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), using an amidolytic method. Fibrinolysis, quantified as increased PAI-1 activity, was reduced in both claudicant groups relative to healthy controls at baseline. After 6 months of exercise, subjects in the IC-EX group experienced significant improvements in fibrinolytic activity, manifested as a 23% decrease in PAI-1 activity and a 28% increase in tPA activity. No changes occurred in the IC-NONEX group. In the IC-EX group, subjects with the highest initial PAI-1 values experienced the greatest decreases in PAI-1 activity and thus the greatest benefit from exercise., Conclusions: Patients with PAD have impaired fibrinolytic activity, manifested primarily as increases in the inhibitor of fibrinolysis, PAI-1. Six months of exercise training reduced these impairments, and may serve as an intervention to reduce cardiovascular mortality and morbidity in these patients.

Purpose: Impaired endogenous fibrinolysis is an important predictor for increased risk of stroke and myocardial infarction. Acute exercise can enhance fibrinolysis, primarily by stimulating short-term increases in plasma tissue plasminogen activator (tPA), which is postulated to protect against atherothrombotic events. No prior studies have examined the fibrinolytic response to exercise in stroke survivors despite their high risk for recurrent stroke and myocardial infarction. The purpose of this study was to assess the fibrinolytic response to acute submaximal exercise in chronic hemiparetic stroke patients., Methods: Eighteen (16 men, 2 women) untrained stroke patients with chronic hemiparetic gait deficits volunteered for participation in this single session exercise study. Fasting blood samples for determination of tPA and plasminogen activator inhibitor (PAI-1) enzyme activities were obtained before, immediately after, and 60 min after submaximal treadmill walking. Patients walked at 60% maximal heart rate reserve (low-moderate intensity) for a cumulative total of 20 min., Results: The exercise bout increased tPA activity by 79% (P < 0.01) and decreased PAI-1 activity by 18% (P < 0.01). At 1 h after completing the walking exercise, plasma tPA activity levels were still significantly elevated (43%,P < 0.01), and PAI-1 activity levels were 25% lower (P < 0.01) than baseline., Conclusions: These findings demonstrate that a single bout of aerobic walking exercise can improve fibrinolysis profiles in chronic stroke patients. Significant increases in endogenous tPA and reductions in PAI-1 activity persist for at least 1 h after exercise cessation. The implications are that alterations in physical activity during the day may modify clot lysing potential, thereby affecting atherothrombotic risk.

Objective: To investigate the hypothesis that treadmill training will improve peak fitness, while lowering the energy cost of hemiparetic gait in chronic stroke patients., Design: Noncontrolled exercise intervention study with repeated-measures analysis., Setting: Hospital-based senior exercise research center., Participants: Twenty-three patients (mean age +/- standard deviation [SD] 67 +/- 8 yr) with chronic hemiparetic gait after remote (>6 mo) ischemic stroke., Intervention: Three 40-minute sessions of treadmill exercise weekly for 6 months., Main Outcome Measures: Peak exercise capacity (VO2peak) and rate of oxygen consumption during submaximal effort treadmill walking (economy of gait) by open circuit spirometry and ambulatory workload capacity before and after 3 and 6 months of training., Results: Patients who completed 3 months of training (n = 21) increased their VO2peak +/- SD from 15.4 +/- 2.9 mL x kg(-1) x min(-1) to 17.0 +/- 4.4 mL x kg(-1) x min(-1) (p <.02) and lowered their oxygen demands of submaximal effort ambulation from 9.3 +/- 2 mL x kg(-1) x min(-1) to 7.9 +/- 1.5 mL x kg(-1) x min(-1) (p =.002), which enabled them to perform the same constant-load treadmill task using 20% less of their peak exercise capacity (62.3% +/- 17.2% vs 49.9% +/- 19.3%, p <.002). Gains in VO2peak and economy of gait plateaued by 3 months, while peak ambulatory workload capacity progressively increased by 39% (p <.001) over 6 months., Conclusions: Treadmill training improves physiologic fitness reserve in chronic stroke patients by increasing VO2peak while lowering the energy cost of hemiparetic gait, and increases peak ambulatory workload capacity. These improvements may enhance functional mobility in chronic stroke patients., (Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation)

Background and Purpose: Chronic upper extremity hemiparesis is a leading cause of functional disability after stroke. We investigated the hypothesis that bilateral arm training with rhythmic auditory cueing (BATRAC) will improve motor function in the hemiparetic arm of stroke patients., Methods: In this single group pilot study we determined the effects of 6 weeks of BATRAC on 14 patients with chronic hemiparetic stroke (median time after stroke, 30 months) immediately after training and at 2 months after training. Four 5-minute periods per session (3 times per week) of BATRAC were performed with the use of a custom-designed arm training machine., Results: The patients showed significant and potentially durable increases in the following: Fugl-Meyer Upper Extremity Motor Performance Test of impairment (P<0.0004), Wolf Motor Function Test (performance time measure, P<0.02), and University of Maryland Arm Questionnaire for Stroke measuring daily use of the hemiparetic arm (P<0.002). Isometric strength improved in elbow flexion (P<0.05) and wrist flexion (P<0.02) for the paretic arm and in elbow flexion (P<0.02) and wrist extension (P<0.02) for the nonparetic arm. Active range of motion improved for paretic-side shoulder extension (P<0.01), wrist flexion (P<0.004), and thumb opposition (P<0.002), and passive range of motion improved for paretic wrist flexion (P<0.03)., Conclusions: -Six weeks of BATRAC improves functional motor performance of the paretic upper extremity as well as a few changes in isometric strength and range of motion. These benefits are largely sustained at 8 weeks after training cessation.

Background and Purpose: Despite the belief that after cerebral infarction only limited functional gains are possible beyond the subacute period, we tested the hypothesis that a 12-week program of "task-oriented" treadmill exercise would increase muscle strength and decrease spastic reflexes in chronic hemiparetic patients., Methods: Fourteen subjects, aged 66+/-3 (mean+/-SEM) years, with residual gait deviations due to remote stroke (>6 months), underwent repeated measures of reflexive and volitional (concentric and eccentric) torque with use of isokinetic dynamometry on the hamstring musculature bilaterally. Torque output was measured at 4 angular velocities (30(o), 60(o), 90(o), and 120(o)/s)., Results: After 3 months of 3 times/wk low-intensity aerobic exercise, there were significant main effects (2 legs [P<0.01]x2 times [P<0. 01]x4 angular velocities [P<0.05]) for concentric torque production. Torque/time production in the concentric mode also improved significantly in the paretic (50%, P<0.01) and nonparetic hamstrings (31%, P<0.01). Eccentric torque/time production increased by 21% (P<0.01) and 22% (P<0.01) in the paretic and nonparetic hamstrings, respectively. Passive (reflexive) torque/time generation in the paretic hamstrings decreased by 11% (P<0.027). Reflexive torque/time was unchanged in the nonparetic hamstrings (P=0.45)., Conclusions: These findings provide evidence that progressive treadmill aerobic exercise training improves volitional torque and torque/time generation and reduces reflexive torque/time production in the hemiparetic limb. Strength changes associated with improved functional mobility in chronic hemiparetic stroke survivors after treadmill training will be reported in future articles.

Background and Purpose: Elevated energy costs of hemiparetic gait contribute to functional disability after stroke, particularly in physically deconditioned older patients. We investigated the effects of 6 months of treadmill aerobic exercise training on the energy expenditure and cardiovascular demands of submaximal effort ambulation in stroke patients with chronic hemiparetic gait., Methods: Nine older stroke patients with chronic hemiparetic gait were enrolled in a 6-month program of low-intensity aerobic exercise using a graded treadmill. Repeated measures of energy expenditure based on steady state oxygen consumption during a standardized 1-mph submaximal effort treadmill walking task were performed before and after training., Results: Six months of exercise training produced significant reductions in energy expenditure (n = 9; 3.40 +/- 0.27 versus 2.72 +/- 0.25 kcal/min [mean +/- SEM]; P < .005) during a given submaximal effort treadmill walking task. Repeated measures analysis in the subset of patients (n = 8) tested at baseline and after 3 and 6 months revealed that reductions in energy expenditure were progressive (F = 11.1; P < .02) and that exercise-mediated declines in both oxygen consumption (F = 9.7; P < .02) and respiratory exchange ratio (F = 13.4; P < .01) occurred in a strong linear pattern. These stroke patients could perform the same standardized submaximal exercise task at progressively lower heart rates after 3 months (96 +/- 4 versus 87 +/- 4 beats per minute) and 6 months of training (82 +/- 4 beats per minute; F = 35.4; P < .002)., Conclusions: Six months of low-intensity treadmill endurance training produces substantial and progressive reductions in the energy expenditure and cardiovascular demands of walking in older patients with chronic hemiparetic stroke. This suggests that task-oriented aerobic exercise may improve functional mobility and the cardiovascular fitness profile in this population.