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Mechanical impedance of the ankle is known to influence key aspects of ankle function. We investigated the effects of robot-assisted ankle training in people with chronic stroke on the paretic ankle's passive stiffness and its relationship to overground gait function. Over 6 wk, eight participants with residual hemiparetic deficits engaged in a visuomotor task while seated that required dorsiflexion (DF) or plantar flexion (PF) of their paretic ankle with an ankle robot ("anklebot") assisting as needed. Passive ankle stiffness (PAS) was measured in both the trained sagittal and untrained frontal planes. After 6 wk, the PAS decreased in both DF and PF and reverted into the variability of age-matched controls in DF. Changes in PF PAS correlated strongly with gains in paretic step lengths (Spearman rho = -0.88, p = 0.03) and paretic stride lengths (Spearman rho = -0.82, p = 0.05) during independent floor walking. Moreover, baseline PF PAS were correlated with gains in paretic step lengths (Spearman rho = 0.94, p = 0.01), paretic stride lengths (Spearman rho = 0.83, p = 0.05), and single-support stance duration (Spearman rho = 0.94, p = 0.01); and baseline eversion PAS were correlated with gains in cadence (Spearman rho = -0.88, p = 0.03). These findings suggest that ankle robot-assisted, visuomotor-based, isolated ankle training has a positive effect on paretic ankle PAS that strongly influences key measures of gait function.

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.

The Unified Parkinson's Disease Rating Scale (UPDRS) is a widely applied index of disease severity. Our objective was to assess the utility of UPDRS for predicting peak aerobic capacity (VO2 peak) and ambulatory function. Participants (n = 70) underwent evaluation for UPDRS (Total and Motor ratings), VO2 peak, 6-minute walk distance (6MW), and 30-foot self-selected walking speed (SSWS). Using regression, we determined the extent to which the Total and Motor UPDRS scores predicted each functional capacity measure after adjusting for age and sex. We also tested whether adding the Hoehn and Yahr scale (H-Y) to the model changed predictive power of the UPDRS. Adjusted for age and sex, both the Total UPDRS and Motor UPDRS subscale failed to predict VO2 peak. The Total UPDRS did weakly predict 6MW and SSWS (both p < 0.05), but the Motor UPDRS subscale did not predict these ambulatory function tests. After adding H-Y to the model, Total UPDRS was no longer an independent predictor of 6MW but remained a predictor of SSWS. We conclude that Total and Motor UPDRS rating scales do not predict VO2 peak, but that a weak relationship exists between Total UPDRS and measures of ambulatory function.

Changes in the biomechanics of gait may alter the energy requirements of walking in Parkinson's Disease (PD). This study investigated economy of gait during submaximal treadmill walking in 79 subjects with mild to moderate PD and the relationship between gait economy and 6-minute walk distance (6 MW). Oxygen consumption (VO(2)) at the self-selected treadmill walking speed averaged 64% of peak oxygen consumption (VO(2) peak). Submaximal VO(2) levels exceeded 70% of VO(2) peak in 30% of the subjects. Overall the mean submaximal VO(2) was 51% higher than VO(2) levels expected for the speed and grade consistent with severe impairment in economy of gait. There was an inverse relationship between economy of gait and 6MW (r = -0.31, P < 0.01) and with the self-selected walking speed (r = -0.35, P < 0.01). Thus, the impairment in economy of gait and decreased physiologic reserve result in routine walking being performed at a high percentage of VO(2) peak.

Purpose: Maximal or peak aerobic capacity (VO(2peak)) during a maximal-effort graded exercise test is considered by many to be the "gold standard" outcome for assessing the effect of exercise training on cardiorespiratory fitness. The reliability of this measure in Parkinson disease (PD) has not been established, where the degree of motor impairment can vary greatly and is influenced by medications. This study examined the reliability of VO(2peak) during a maximal-effort graded exercise test in subjects with PD., Methods: Seventy healthy middle-aged and older subjects with PD Hoehn and Yahr stage 1.5-3 underwent a screening/acclimatization maximal-effort treadmill test followed by two additional maximal-effort treadmill tests with repeated measurements of VO(2peak). A third VO(2peak) test was performed in a subset of 21 subjects., Results: The mean VO(2peak) measurement was 2.4% higher in the second test compared with the first test (21.42 ± 4.3 vs 21.93 ± 4.50 mL·kg(-1)·min(-1), mean ± SD, P = 0.03). The intraclass correlation coefficients (ICC) for VO(2peak) expressed either as milliliters per kilogram per minute or as liters per minute were highly reliable, with ICC of 0.90 and 0.94, respectively. The maximum HR (ICC of 0.91) and final speed achieved during the tests (ICC of 0.94) were also highly reliable, with the respiratory quotient being the least reliable of the parameters measured (ICC of 0.65)., Conclusions: Our results demonstrate that measurement of VO(2peak) is reliable and repeatable in subjects with mild to moderate PD, thereby validating use of this parameter for assessing the effects of exercise interventions on cardiorespiratory fitness.

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: Task-oriented therapies such as treadmill exercise can improve gait velocity after stroke, but slow velocities and abnormal gait patterns often persist, suggesting a need for additional strategies to improve walking., Objectives: To determine the effects of a 6-week visually guided, impedance controlled, ankle robotics intervention on paretic ankle motor control and gait function in chronic stroke., Methods: This was a single-arm pilot study with a convenience sample of 8 stroke survivors with chronic hemiparetic gait, trained and tested in a laboratory. Subjects trained in dorsiflexion-plantarflexion by playing video games with the robot during three 1-hour training sessions weekly, totaling 560 repetitions per session. Assessments included paretic ankle ranges of motion, strength, motor control, and overground gait function., Results: Improved paretic ankle motor control was seen as increased target success, along with faster and smoother movements. Walking velocity also increased significantly, whereas durations of paretic single support increased and double support decreased., Conclusions: Robotic feedback training improved paretic ankle motor control with improvements in floor walking. Increased walking speeds were comparable with reports from other task-oriented, locomotor training approaches used in stroke, suggesting that a focus on ankle motor control may provide a valuable adjunct to locomotor therapies.

Our objective in this study was to assess passive mechanical stiffness in the ankle of chronic hemiparetic stroke survivors and to compare it with those of healthy young and older (age-matched) individuals. Given the importance of the ankle during locomotion, an accurate estimate of passive ankle stiffness would be valuable for locomotor rehabilitation, potentially providing a measure of recovery and a quantitative basis to design treatment protocols. Using a novel ankle robot, we characterized passive ankle stiffness both in sagittal and in frontal planes by applying perturbations to the ankle joint over the entire range of motion with subjects in a relaxed state. We found that passive stiffness of the affected ankle joint was significantly higher in chronic stroke survivors than in healthy adults of a similar cohort, both in the sagittal as well as frontal plane of movement, in three out of four directions tested with indistinguishable stiffness values in plantarflexion direction. Our findings are comparable to the literature, thus indicating its plausibility, and, to our knowledge, report for the first time passive stiffness in the frontal plane for persons with chronic stroke and older healthy adults.

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.

Cerebrovascular accident (stroke) often results in impaired motor control and persistent weakness that may lead to chronic disability, including deficits in gait and balance function. Finding ways to restore motor control may help reduce these deficits; however, little is known regarding the capacity or temporal profile of short-term motor adaptations and learning at the hemiparetic ankle. Our objective was to determine the short-term effects of a single session of impedance-controlled ankle robot ("anklebot") training on paretic ankle motor control in chronic stroke. This was a double-arm pilot study on a convenience sample of participants with chronic stroke (n = 7) who had residual hemiparetic deficits and an equal number of age- and sex-matched nondisabled control subjects. Training consisted of participants in each group playing a target-based video game with the anklebot for an hour, for a total of 560 movement repetitions in dorsiflexion/plantar flexion ranges followed by retest 48 hours later. Task difficulty was adjusted to ankle range of motion, with robotic assistance decreased incrementally across training. Assessments included robotic measures of ankle motor control on unassisted trials before and after training and at 48 hours after training. Following exposure to the task, subjects with stroke improved paretic ankle motor control across a single training session as indexed by increased targeting accuracy (21.6 +/- 8.0 to 31.4 +/- 4.8, p = 0.05), higher angular speeds (mean: 4.7 +/- 1.5 degrees/s to 6.5 +/- 2.6 degrees/s, p < 0.01, peak: 42.8 +/- 9.0 degrees/s to 45.6 +/- 9.4 degrees/s, p = 0.03), and smoother movements (normalized jerk: 654.1 +/- 103.3 s(-2) to 537.6 +/- 86.7 s(-2), p < 0.005, number of speed peaks: 27.1 +/- 5.8 to 23.7 +/- 4.1, p < 0.01). In contrast, nondisabled subjects did not make statistically significant gains in any metric after training except in the number of successful passages (32.3 +/- 7.5 to 36.5 +/- 6.4, p = 0.006). Gains in all five motor control metrics were retained (p > 0.05) at 48 hours in both groups. Robust maintenance of motor adaptation in the robot-trained paretic ankle over 48 hours may be indicative of short-term motor learning. Our initial results suggest that the anklebot may be a flexible motor learning platform with the potential to detect rapid changes in ankle motor performance poststroke.

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.

Background: Cognitive deficits impede stroke recovery. Aerobic exercise (AEX) improves cognitive executive function (EF) processes in healthy individuals, although the learning benefits after stroke are unknown., Objective: To understand AEX-induced improvements in EF, motor learning, and mobility poststroke., Methods: Following cardiorespiratory testing, 38 chronic stroke survivors were randomized to 2 different groups that exercised 3 times a week (45-minute sessions) for 8 weeks. The AEX group (n = 19; 9 women; 10 men; 64.10 +/- 12.30 years) performed progressive resistive stationary bicycle training at 70% maximal heart rate, whereas the Stretching Exercise (SE) group (n = 19; 12 women; 7 men; 58.96 +/- 14.68 years) performed stretches at home. Between-group comparisons were performed on the change in performance at "Post" and "Retention" (8 weeks later) for neuropsychological and motor function measures., Results: VO(2)max significantly improved at Post with AEX (P = .04). AEX also improved motor learning in the less-affected hand, with large effect sizes (Cohen's d calculation). Specifically, AEX significantly improved information processing speed on the serial reaction time task (SRTT; ie, "procedural motor learning") compared with the SE group at Post (P = .024), but not at Retention. Also, at Post (P = .038), AEX significantly improved predictive force accuracy for a precision grip task requiring attention and conditional motor learning of visual cues. Ambulation and sit-to-stand transfers were significantly faster in the AEX group at Post (P = .038), with balance control significantly improved at Retention (P = .041). EF measurements were not significantly different for the AEX group., Conclusion: AEX improved mobility and selected cognitive domains related to motor learning, which enhances sensorimotor control after stroke.

Stroke disability is attributed to upper motor neuron deficits resulting from ischemic brain injury. We have developed proteome maps of the Vastus lateralis to examine the effects of ischemic brain injury on paretic skeletal muscle myofilament proteins. Proteomics analyses from seven hemiparetic stroke patients have detected a decrease of three troponin T isoforms in the paretic muscle suggesting that myosin-actin interactions may be attenuated. We propose that ischemic brain injury may prevent troponin T participation in complex formation thereby affecting the protein interactions associated with excitation-contraction coupling. We have also detected a novel skeletal troponin T isoform that has a C-terminal variation. Our data suggest that the decreased slow troponin T isoform pools in the paretic limb may contribute to the gait deficit after stroke. The complexity of the neurological deficit on Vastus lateralis is suggested by the multiple changes in proteins detected by our proteomics mapping.

Objective: Adiponectin is an anti-inflammatory and insulin-sensitizing adipokine produced by adipose tissue. The purpose of this study was to determine the relationships between adiponectin and glucose metabolism in stroke survivors and to compare adiponectin levels between patients with stroke and nonstroke control subjects similar in age, sex, and body mass index., Methods: In all, 52 stroke survivors (35 men, 17 women) and 33 nonstroke control subjects (22 men, 11 women) had plasma adiponectin levels measured by RIA, an oral glucose tolerance test, and a peak oxygen consumption-graded treadmill test. Insulin resistance (IR) and insulin sensitivity were assessed using the homeostasis model assessment for IR (HOMA-IR) and insulin sensitivity index (ISI(M))., Results: Adiponectin levels were positively associated with age (r = 0.32, P < .05) and negatively associated with glucose homeostasis (fasting glucose: r = -0.42; insulin: r = -0.36; Glucose at (120 min): r = -0.39; HOMA-IR: r = -0.45; and ISI(M): r = 0.44, all P < .01) in stroke survivors. Adiponectin levels were significantly different among normal glucose-tolerant, impaired glucose-tolerant, and diabetic patients with stroke (11.1 +/- 0.99 v 9.56 +/- 0.99 v 5.75 +/- 1.55 ng/mL, P < .05). Adiponectin levels were 62% higher in patients with stroke than control subjects (9.29 +/- 0.62 v 5.80 +/- 0.40 ng/mL, P < .001) despite greater fasting insulin levels (81%) and 120-minute insulin (70%) in stroke survivors than control subjects (P < .05). HOMA-IR was 78% higher and ISI(M) was 81% lower in stroke survivors than control subjects (P < .05)., Conclusions: Plasma adiponectin levels are associated with age and insulin sensitivity but not adiposity in stroke survivors. The paradoxical finding that the more IR stroke survivors had higher adiponectin levels than more insulin-sensitive control subjects suggests that perhaps anti-inflammatory cytokines increase to counter an inflamed and IR state in stroke survivors.

Objective: Reduced capillarization in hemiparetic skeletal muscle of chronic stroke patients can limit insulin, glucose, and oxygen supply to muscle, thereby contributing to impaired glucose metabolism and cardiovascular deconditioning. We hypothesized that compared to sedentary controls, stroke subjects have reduced skeletal muscle capillarization that is associated with glucose intolerance and reduced peak oxygen consumption (Vo(2peak))., Methods: Twelve chronic stroke subjects (ages, 62.1+/-2.8 years), and matched sedentary controls with impaired (n=12) or normal (n=12) glucose tolerance underwent oral glucose tolerance tests, exercise tests, and vastus lateralis biopsies., Results: Stroke subjects had lower capillarization in hemiparetic muscle than in nonparetic muscle and normal glucose tolerant controls ( approximately 22 and approximately 28%, respectively; P<0.05) and had similar bilateral capillarization, compared to controls with impaired glucose tolerance. Capillary density in hemiparetic muscle inversely correlated with 120-minute glucose (r=-0.70, P<0.01) and glucose area under the curve (r=-0.78, P<0.01). Vo(2peak) was approximately 40% lower in stroke subjects, compared to controls (P<0.001), but did not correlate with capillarization (P=n.s.)., Conclusions: Hemiparetic muscle capillarization is reduced after stroke, and reduced capillarization is associated with glucose intolerance in stroke and control subjects. Interventions to increase skeletal muscle capillarization may prove beneficial for improving glucose metabolism in chronic stroke patients.

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.

Transcranial magnetic stimulation (TMS) non-invasively measures excitability of central motor pathways in humans and is used to characterize neuroplasticity after stroke. Using TMS to index lower extremity neuroplasticity after gait rehabilitation requires test-retest reliability. This study assesses the reliability of TMS-derived variables measured at bilateral quadriceps of chronic hemiparetic stroke survivors. Results support using measures of both paretic and nonparetic motor threshold, motor evoked potential (MEP) latencies; and nonparetic MEP amplitudes. Implications for longitudinal research are discussed.

Skeletal muscle phenotype alterations following hemiparetic stroke contribute to disabilities associated with stroke. The phenotypic response following stroke is undefined. This investigation examined the myosin heavy chain (MHC) composition of the vastus lateralis (VL) of stroke survivors in paretic (P) and nonparetic (NP) muscle. Protein obtained from VL of 10 stroke survivors was isolated and purified, and MHC gel electrophoresis was performed. The MHC bands were quantified, and a paired sample two-tailed T test with significance set at p < or = 0.05 was performed. MHC I expression was significantly less in P versus NP VL (.93 vs. 1.00 arbitrary units [AU]). Significantly more IIx MHC was found in the P versus NP VL (1.33 vs. 1.0). No significant differences in type IIa MHC (1.07 P vs. 1.00 NP) were found. These changes in MHC composition suggest an alteration in muscle function due to stroke or the altered activity patterns of muscle following stroke.

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.

Background: Self-report measures of physical activity have well-known drawbacks, and physiologic measures alone do not account for behavioral variables important in the perception and performance of physical activity. Therefore, we considered multiple measures to quantify physical activity in community-dwelling men and women with chronic stroke., Methods: This analysis included data from a volunteer sample of 87 individuals at least 6 months poststroke. Physical activity was measured using self-report questionnaires, step activity monitors, self-efficacy expectations related to exercise, and VO(2)peak from treadmill testing, and a model of physical activity was tested., Results: Most of the variance in objective physical activity was explained by VO(2)peak, and most of the variance in subjective physical activity was explained by self-efficacy expectations. There were significant discrepancies between subjective and objective findings., Conclusion: This study helps to understand the perspective of stroke survivors with regard to physical activity.

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.

Background and Purpose: Insulin resistance and glucose intolerance are highly prevalent after stroke, contributing to worsening cardiovascular disease risk and a predisposition to recurrent stroke. Treadmill exercise training (T-AEX) increases aerobic capacity (Vo(2) peak) in chronic stroke patients, suggesting intensity levels that may be adequate to improve glucose metabolism. We compared the effects of a progressive T-AEX intervention to an attention-matched stretching intervention (CONTROL) on glucose tolerance and indices of insulin sensitivity in stroke survivors., Methods: Participants had hemiparetic gait after remote (>6 months) ischemic stroke. They were randomized to 6-month T-AEX or a duration matched reference CONTROL program of supervised stretching exercises. Main outcome measures were glucose and insulin responses during a 3-hour oral glucose tolerance test (OGTT)., Results: Forty-six subjects (T-AEX=26, CONTROL=20) completed OGTT testing before and after the interventions. T-AEX increased Vo(2) peak (+15% versus -3% Delta, P<0.01) compared with CONTROL. There were significant reductions in fasting insulin (-23% versus +9% Delta, P<0.05) and the total integrated 3-hour insulin response (-24% versus +3% Delta, P<0.01) in T-AEX compared with CONTROL. In patients with abnormal glucose tolerance at baseline, T-AEX resulted in a significant 14% decrease in 3-hour glucose response (n=12, P<0.05). Fifty-eight percent of T-AEX participants with abnormal baseline OGTT (7 of 12) improved glucose tolerance status at 2 hours compared with <10% (1 of 11) of impaired CONTROLS (P<0.05)., Conclusions: These preliminary findings suggest that progressive aerobic exercise can reduce insulin resistance and prevent diabetes in hemiparetic stroke survivors. Larger clinical trials are needed to definitively establish the use of structured exercise training for stimulating metabolic improvement poststroke.

Objectives: To test the hypothesis that quantitative measures of cardiovascular fitness and ambulatory function differ in Black and White hemiparetic stroke survivors., Design: Cross-sectional analysis., Setting: Outpatient academic medical center., Participants: Total of 118 hemiparetic stroke survivors., Main Outcome Measures: Cardiovascular fitness was measured as VO2 peak and ambulatory function using the six-minute walk distance and 30-foot walking velocity in medically screened, community-dwelling stroke survivors., Results: In 118 subjects (56% Black and 44% White), no differences were seen in 1) VO2 peak between Black or White men (15.0+/-4.3 vs. 15.1+/-3.9 mL/kg/minute) or women (11.5+/-2.7 vs. 12.3+/-3.7 mL/kg/minute); 2) six-minute walk distance between Black or White men (223+/-112 m vs 226+/-132 m) or women (198+/-100 vs 157+/-93 m); or 3) 30-foot walking velocity between Black or White men (0.60+/-0.27 m/second vs 0.61+/-0.31 m/ second) or women (0.50+/-0.21 m/second vs 0.41+/-0.23 m/second)., Conclusion: No racial differences were seen in the degree of physical deconditioning in a selected population of community dwelling hemiparetic stroke survivors.

Background: Abnormalities of endogenous fibrinolysis are linked to diabetic macrovascular disease; whether key vascular endothelial regulatory proteins, such as tissue plasminogen activator (tPA), are altered in diabetic neuropathy microvasculature is unknown. This neuropathologic case: control study investigates the hypothesis that tPA expression is regionally deficient in microvessels in human diabetic neuropathy., Methods: tPA and von Willebrand factor (vWF), a vascular endothelial cell marker, are detected on vascular endothelium by immunoperoxidase methods with specific antibodies on formalin fixed paraffin embedded sural nerve biopsies from six diabetic and six axonal neuropathy control nerves without vasculopathy. The proportion of microvessels in each nerve region expressing tPA is determined by the ratio of tPA positive vessels/total vWF positive vessels on serial sections., Results: tPA expression is lower in diabetic neuropathy cases compared to controls in all regions, including epineurial (62.4 +/- 8.6% vs 91.0 +/- 1.6%, p < 0.02) and endoneurial microvessels (51.7 +/- 7.1% vs 91.5 +/- 2.9%, p < 0.001)., Conclusions: These results demonstrate a four- to sixfold increase in the number of peripheral nerve microvessels lacking immunodetectable tissue plasminogen activator in the epineurial and endoneurial vessels in diabetes, suggesting that impaired endogenous fibrinolysis might contribute to microvascular ischemia in human diabetic neuropathy.

Numerous electroencephalography (EEG) studies have shown that neurophysiological signals change in response to visual and sensory adaptations in upper extremity tasks. However, this has not been clearly studied in the lower extremity. In this study, we evaluated how sensory loading affects brain activations related to knee movement. Thirty-two channel EEG was recorded while ten subjects performed knee extension in four different conditions: no weight and no visual target (NWNT), weight affixed to the ankle and no visual target (WNT), no weight and a visual target (NWT), and both weight and target (WT). Surface electromyography (EMG) was recorded from the vastus medialis and vastus lateralis muscles to determine onset of the movement. EEG was epoched from -4.5 s before to 1 s after EMG onset. Epochs were averaged to acquire movement-related cortical potentials (MRCPs) of each task condition. MRCP amplitude during the pre-movement period from -2 s to EMG onset was evaluated at electrodes over motor, sensory, frontal, and parietal areas. The amplitude of the pre-movement potentials for the conditions was different across areas of interest. Over the motor area, NWNT had lower amplitude than any other condition and WT had higher amplitude than any other condition. There was no difference between unimodal NWT and WNT conditions. Mesial frontal and parietal areas showed larger MRCP to the bimodal condition than either unimodal or NWNT conditions. The parietal cortex was the only region that showed a difference between unimodal conditions with greater amplitude for NWT condition. Information concerning added sensory demand is processed by the motor cortex in a way that may be indifferent to the type of modality, but is influenced by the quantity of modalities at the level of the knee. Other brain structures such as parietal and premotor cortices respond based on the modality type to help plan appropriate strategies for motor control in response to sensory manipulations. This suggests that additional task demands in motor training may create a rich sensory environment that may be beneficial in promoting optimal neuromotor recovery.

Background: Stroke survivors are at significant risk for recurrent stroke and cardiovascular disease. Inadequately managed modifiable risk factors increase the threat of recurrent stroke, development of new comorbidities, and double the risk of premature mortality. The purpose of this study was to determine the prevalence of modifiable cardiovascular risk factors in stroke survivors who completed a research screening evaluation for entry into exercise rehabilitation studies. The sample collected between January 2001 and June 2005 evaluated 364 community-dwelling men and women aged 34 to 88 years living in Baltimore, Maryland., Methods: Each participant's risk profile was evaluated from data obtained during a medical history and physical examination and from laboratory analysis of a fasting blood sample. Current practice guidelines were used to define risk categories., Results: Ninety-nine percent of participants had at least one suboptimally controlled risk factor. Ninety-one percent had two or more concurrent risk factors inadequately treated. Eighty percent of the participants had prehypertension or hypertension, 67% were overweight or obese, 60% had suboptimal low-density lipoprotein, 45% had impaired fasting glucose, 34% had low high-density lipoprotein, and 14% were current smokers, while reportedly receiving routine medical care., Conclusions: These findings confirm that cardiovascular risk factors remain inadequately managed in stroke survivors, increasing the chance for repeat stroke and cardiovascular event. Systematic assessment of this vulnerable population is imperative at every healthcare encounter.

Purpose: The purpose of this study was to describe household and community ambulatory activity profiles and their relationship to fatigue and cardiovascular fitness in a sample of men and women with chronic hemiparetic stroke., Method: We quantified community-based ambulatory activity profiles in terms of step counts and intensity, along with cardiovascular fitness and fatigue severity, in a convenience sample of 79 men and women with chronic hemiparetic stroke., Results: As captured by daily step activity monitoring, participants demonstrated extremely low step counts (1389 +/- 797 steps/day), and almost no step activity at high intensity (78 +/- 168 steps/day at a rate of >or=30 steps/ minute). Mean high intensity activity constituted less than 3 minutes/day. The mean VO2 peak was 13.02 +/- 4.26 mL/kg/min, consistent with profound aerobic deconditioning. Total, low, and high intensity ambulatory activity were associated with VO2 peak. Mean fatigue severity was 3.28 +/- 1.36 on a scale of 7.00, with 42% of the sample reporting severe fatigue. There were no statistically significant correlations between fatigue severity and ambulatory activity or fitness measures., Conclusion: Our results show that step activity intensity is strongly associated with cardiovascular fitness, lending credence to the hypothesis that rehabilitation interventions that build aerobic conditioning can influence daily activity. The challenge is to appreciate the features of ambulatory behavior after stroke and to use this information to integrate both exercise interventions and behavioral components into the successful translation of structured activities into home and community routines.

Objectives: To investigate the relationship of cardiovascular fitness (Vo(2)peak), neurologic deficits in balance and leg strength, and body composition to ambulatory function after stroke and to determine whether these relationships differ between those with milder versus more severe gait deficits., Design: Cross-sectional correlation study., Setting: Outpatient clinic of an academic medical center., Participants: Seventy-four people (43 men, 31 women; mean age +/- standard deviation, 64+/-10y) with chronic hemiparetic stroke., Interventions: Not applicable., Main Outcome Measures: Thirty-foot (9.1-m) walk velocity, 6-minute walk distance, Vo(2)peak, Berg Balance Scale score, bilateral quadriceps eccentric torque, total and regional lean mass, and percentage of fat mass., Results: Short-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, percentage of body fat, and paretic lean mass but not with nonparetic lean mass. Long-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, and paretic lean mass but not with percentage of body fat or nonparetic lean mass. Stepwise regression showed that cardiovascular fitness, balance, and paretic leg strength were independently associated with long-distance walking (r(2)=.60, P<.001). Variance in long-distance walking was largely explained by balance for those who walked more slowly (<.48m/s) for short distances (r(2)=.42, P<.001) and by cardiovascular fitness for those who walked more quickly (>.48m/s) for short distances (r(2)=.26, P=.003)., Conclusions: Short-distance walking after stroke is related to balance, cardiovascular fitness, and paretic leg strength. Long-distance walking ability differs by gait deficit severity, with balance more important in those who walk more slowly and cardiovascular fitness playing a greater role in those who walk more quickly. Improved understanding of the factors that predict ambulatory function may assist the design of individualized rehabilitation strategies across the spectrum of gait deficit severity in those with hemiparetic stroke.

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.

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.

We assessed the interactive effect of genetic polymorphisms and exercise training on fibrinolysis in 50 - 75 yr old men (n = 17) and women (n = 28). Subjects had tissue plasminogen activator (t-PA) antigen levels and activity and plasminogen activator inhibitor-1 (PAI-1) activity measured before and after 6 mo of endurance-exercise training. Subject's DNA was typed for the PAI-1 4 G/5 G and t-PA I/D variants. Baseline PAI-1 activity, t-PA activity, and t-PA antigen levels were not different among PAI-1 or t-PA genotype groups. Overall, exercise training did not change PAI-1 activity (- 0.43 +/- 0.81 IU/mL, p = NS), increased t-PA activity (0.37 +/- 0.16 IU/mL, p = 0.02), and decreased t-PA antigen levels (- 0.88 +/- 0.20 ng/mL, p < 0.001). Although the differences in changes with training were not significant among genotype groups, significant t-PA antigen level improvements were evident only in PAI-1 4 G allele carriers and significant t-PA activity increases only in PAI-1 4 G homozygotes. t-PA genotype affected the training-induced t-PA antigen level improvements (p = 0.033) after covarying for gender and baseline t-PA antigen levels, with the smallest and largest reductions in the D homozygotes and I/D heterozygotes, respectively. These findings could have important treatment implications for the use of exercise training to reduce CV disease and thrombotic risk in older men and women.

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., (Copyright (c) 2006 S. Karger AG, Basel.)

Stroke is the leading cause of disability in older Americans, and survivors tend to be sedentary, thereby risking loss of functional gains achieved during rehabilitation and increasing cardiovascular risk. Studies of motivation to exercise in older adults suggest that self-efficacy and outcome expectations are key determinants of initiation and adherence to exercise programs. This study tested a theoretical model of physical activity in stroke survivors. A survey of exercise beliefs and patterns was sent to National Stroke Association stroke support groups. Responses from 312 stroke survivors (mean age 63 years, 57% female, 70% White) indicated that only 31% exercised four times weekly. Self-efficacy and outcome expectations for exercise, before exercise history, and physician recommendation all directly and indirectly influenced self-reported exercise behavior and accounted for 33% of the total variance in exercise behavior. Model testing supported the theory and the model fit the data. Interventions to strengthen self-efficacy and outcome expectations for exercise, along with reminders for clinicians to encourage regular exercise programs, may increase the likelihood of initiating and maintaining an exercise program, potentially improving physical function and cardiovascular fitness in this population.

Stroke patients have profound cardiovascular and muscular deconditioning, with metabolic fitness levels that are about half those found in age-matched sedentary controls. Physical deconditioning, along with elevated energy demands of hemiparetic gait, define a detrimental combination termed diminished physiological fitness reserve that can greatly limit that can greatly limit performance of activities of daily living. The physiological features that underlie worsening metabolic fitness in the chronic phase of stroke include gross muscular atrophy, altered muscle molecular phenotype, increased intramuscular area fat, elevated tissue inflammatory markers, and diminished peripheral blood flow dynamics. Epidemiological evidence further suggests that the reduced cardiovascular fitness and secondary biological changes in muscle may propagate components of the metabolic syndrome, conferring added morbidity and mortality risk. This article reviews some of the consequences of poor fitness in chronic stroke and the potential biological underpinnings that support a rationale for more aggressive approaches to exercise therapy in this population.

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.

Endurance exercise training improves fibrinolysis, but this training-induced adaptation may differ somewhat between men and women. We sought to determine whether the potential gender differences in training-induced changes in selected fibrinolysis measures were related to changes in adiposity and/or plasma lipoprotein lipid levels. Seventeen men and 28 women, 50-75 years old, who were generally overweight to obese, were assessed for plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) activity, t-PA antigen and plasma lipoprotein-lipid levels, and body composition before and after 6 months of endurance exercise training while on a low-fat diet. At baseline, there were no differences in fibrinolytic measures between the men and women. Baseline levels of these fibrinolytic markers in both men and women were primarily related to other fibrinolytic measures and body composition, with a smaller contribution from plasma high-density lipoprotein cholesterol (HDL-C) levels. Exercise training reduced t-PA antigen levels in both men and women, but the reduction was significantly greater in men (-1.6 +/- 0.3 versus -0.5 +/- 0.2 ng ml(-1), P = 0.007). Exercise training decreased PAI-1 activity more in men than in women (-2.6 +/- 1.4 versus +0.9 +/- 0.9 IU ml(-1), P = 0.03). Men and women both showed increased t-PA activity with exercise training to the same extent (+0.38 +/- 0.12 versus +0.36 +/- 0.24 U ml(-1)). The changes in fibrinolytic measures with exercise training in men and women were correlated with changes in other fibrinolytic measures, although in men abdominal fat changes were a strong predictor of fibrinolytic changes with training. These findings suggest that training-induced improvements in endogenous fibrinolysis markers are somewhat greater in men compared to women and may be more strongly associated with abdominal obesity in men.

Objectives: To determine ambulatory activity in a sample of community-dwelling people with chronic hemiparetic stroke and to examine whether deficits in balance and gait and cardiovascular and metabolic fitness are key determinants of ambulatory activity levels., Design: Descriptive correlational., Setting: Home and community., Participants: Twenty-eight men and 22 women (N=50) over the age 45 years with more than 6 months of hemiparetic gait after ischemic stroke., Interventions: Not applicable., Main Outcome Measures: Ambulatory activity (total daily step activity), mobility deficit severity (Berg Balance Scale [BBS] scores, timed 10-m walks), and cardiovascular fitness (energy costs of hemiparetic gait, peak exercise capacity [VO2peak])., Results: Mean ambulatory activity profiles were extremely low (2837 steps/d vs reported 5000-6000 steps/d in sedentary older adults). Ambulatory activity levels were strongly associated with BBS scores (r=.581, P<.001) and self-selected floor walking velocity (r=.554, P<.001). Participants also had profound cardiovascular deconditioning (mean VO2peak, 11.7+/-2.8 mL.kg(-1).min(-1)). The energy costs of hemiparetic gait were high (8.7+/-1.7 mL.kg(-1).min(-1)), representing 76% of physiologic fitness reserve. Although the relationships of economy of gait and VO2peak to ambulatory activity was not statistically significant, both the VO2peak and the physiologic fitness reserve, as expressed by fractional utilization, were strongly related to balance (r=.374, P=.02; r=-.430, P< .01, respectively.) The BBS predicted 30% of the variance in ambulatory activity., Conclusions: Ambulatory activity levels and cardiovascular fitness in patients with chronic stroke are extremely low. Mobility deficits, particularly in balance, are associated with low ambulatory activity. Balance-related inactivity may be an important factor in deconditioning. Further studies are needed to better understand whether task-oriented exercise enhances balance and whether increases in daily ambulatory activity yield improved cardiovascular fitness in chronic stroke survivors.

Lower extremity paresis poses significant disability to chronic stroke survivors. Unlike for the upper extremity, cortical adaptations in networks controlling the paretic leg have not been characterized after stroke. Here, the hypotheses are that brain activation associated with unilateral knee movement in chronic stroke survivors is abnormal, depends on lesion location, and is related to walking ability. Functional magnetic resonance imaging of unilateral knee movement was obtained in 31 patients 26.9 months (mean, IQ range: 11.3-68.1) after stroke and in 10 age-matched healthy controls. Strokes were stratified according to lesion location. Locomotor disability (30 ft walking speed) did not differ between patient groups (9 cortical, 12 subcortical, 10 brainstem lesions). Significant differences in brain activation as measured by voxel counts in 10 regions of interest were found between controls and patients with brainstem (P = 0.006) and cortical strokes (P = 0.002), and between subcortical and cortical patients (P = 0.026). Statistical parametric mapping of data per group revealed similar activation patterns in subcortical patients and controls with recruitment of contralateral primary motor cortex (M1), supplementary motor area (SMA), and bilateral somatosensory area 2 (S2). Cortical recruitment was reduced in brainstem and cortical stroke. Better walking was associated with lesser contralateral sensorimotor cortex activation in brainstem, but stronger recruitment of ipsilateral sensorimotor and bilateral somatosensory cortices in subcortical and cortical patients, respectively. A post hoc comparison of brainstem patients with and without mirror movements (50%) revealed lesser recruitment of ipsilateral cerebellum in the latter. Subcortical patients with mirror movements (58%) showed lesser bilateral sensorimotor cortex activation. No cortical patient had mirror movements. The data reveal adaptations in networks controlling unilateral paretic knee movement in chronic stroke survivors. These adaptations depend on lesion location and seem to have functional relevance for locomotion.

Objectives: To investigate the utility of a novel microprocessor-linked Step Watch Activity Monitor (SAM) to quantify ambulatory activity after stroke and to evaluate the validity and reliability of conventional accelerometers to measure free-living physical activity in this population., Design: Cross-sectional with repeated measures of 2 separate 48-hour recordings in 17 persons wearing an ankle-mounted SAM and Caltrac, a hip-mounted mechanical accelerometer., Setting: Home and community., Participants: Seventeen subjects with chronic hemiparetic gait after stroke., Interventions: Not applicable., Main Outcome Measures: The SAM derived stride counts per day and Caltrac estimated the daily caloric expenditure of physical activity., Results: SAM data revealed that stroke patients had a mean strides per day +/- standard deviation of 3035+/-1944 and demonstrated a broad range of daily activity profiles (400-6472 strides). SAM test-retest reliability was high across separate monitoring periods (r=.96, P<.001). Although Caltrac also revealed a broad range of daily activity calories (346+/-217 kcal/d; range, 83-1222 kcal/d), reliability was poor (r=.044, P=not significant) and Caltrac accounted for only 64% of the ambulatory activity quantified by the SAM., Conclusions: Microprocessor-linked accelerometer monitoring, but not conventional accelerometers, are accurate and highly reliable for quantifying ambulatory activity levels in stroke patients. These findings support the utility of personal status monitoring of ambulatory activity as an outcomes instrument and metric in programs to increase physical activity and cardiovascular health after stroke.

Background: The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Using data from the Stroke Prevention in Young Women Study, we sought to determine the association between the Ala455Val thrombomodulin polymorphism and the occurrence of ischemic stroke in young women., Methods: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. We compared 141 cases of first ischemic stroke (44% black) among women 15 to 44 years of age with 210 control subjects (35% black) who were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Genotyping of the thrombomodulin Ala455Val polymorphism was performed by pyrosequencing., Results: The A allele (frequency = 0.85) was associated with stroke under the recessive model. After adjustment for age, race, cigarette smoking, hypertension, and diabetes, the AA genotype, compared with the AV and VV genotypes combined, was significantly associated with stroke (odds ratio 1.9, 95% CI 1.1-3.3). The AA genotype was more common among black than white control subjects (81% versus 68%) but there was no significant interaction between the risk genotype and race (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis removing all probable (n = 16) and possible (n = 15) cardioembolic strokes demonstrated an increased association (odds ratio 2.2, 95% CI 1.2-4.2)., Conclusions: Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism.

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.

Self-efficacy has been noted to have a significant impact on exercise behaviors across several clinical conditions, but the influence of self-efficacy and outcome expectations on exercise behaviors in stroke survivors is unknown. This study investigates the reliability and validity of the Short Self-Efficacy for Exercise (SSEE) and Short Outcome Expectations for Exercise (SOEE) scales in stroke survivors and their relationship to regular exercise. A total of 1200 surveys were mailed to stroke support groups throughout North America, with 211 respondents reporting an average age of 66 years and a mean time from stroke of 5.8 years. There was evidence for internal consistency with alpha coefficients of .86 for the SSEE and .90 for the SOEE. Reliability was also estimated using structural equation modeling, and a squared multiple correlation coefficient (R(2)) was used as the estimate of reliability. R(2) values ranged from .38 to .70 in the SSEE and from .47 to .78 in the SOEE. There was evidence of construct validity based on significant lambda values for all items onto their respective constructs. Likewise, there was evidence of construct validity of the SSEE and the SOEE; self-efficacy expectations significantly influenced exercise and accounted for 13% of the variance in exercise, and outcome expectations explained an additional 2% of the variance in exercise, supporting that the SOEE and the SSEE are reliable and valid scales. Measuring these expectations related to exercise post-stroke can establish their influence on exercise behavior and lead to interventions to strengthen these beliefs and improve exercise behavior.

Objective: Treadmill training is a promising tool for retraining gait after stroke. The treadmill induces an immediate shift toward symmetry and longer paretic stance times due to altered muscle activation (active) or the motorized belt (passive). The authors investigated vastus lateralis and medial hamstrings activation differences between treadmill and overground walking in participants with stroke., Methods: Vastus lateralis and medial hamstrings surface electromyography was recorded during velocity-matched overground and treadmill walking in 19 chronically hemiparetic subjects. Variables from ensemble averages of electromyography included burst onset and offset times (% cycle), duration (% cycle), integrated amplitude (mV.% cycle), and onset relative to foot strike (% cycle). Conditions were compared using paired t-tests (alpha = 0.05)., Results: Paretic vastus lateralis onset occurred earlier in the treadmill condition (overground: 47.1%, treadmill: 41.9%, P = 0.01). For nonparetic vastus lateralis in the treadmill condition, onset occurred later (overground: 85.2%, treadmill: 87.6%, P = 0.09), offset occurred earlier (overground: 54.7%, treadmill: 47.8%, P = 0.03), duration was shorter (overground: 69.1%, treadmill: 61.2%, P = 0.01), and integrated amplitude was lower (overground: 14.1, treadmill: 10.6, P = 0.05). Within limbs, paretic vastus lateralis onset occurred earlier relative to paretic foot strike. Nonparetic vastus lateralis onset occurred later relative to nonparetic foot strike., Conclusions: Treadmill walking induces immediate changes in vastus lateralis, but not medial ham-strings, activation patterns. These alterations (earlier paretic vastus lateralis onset and later nonparetic vastus lateralis onset) during treadmill versus overground walking parallel the increased symmetry in gait patterning.

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.

Recovery of motor function after stroke is associated with reorganization in central motor networks. Functional imaging has demonstrated recovery-dependent alterations in brain activation patterns when compared to healthy controls. These alterations are variable across stroke subjects. Factors identified as contributing to this variability are the degree of functional impairment, the time interval since stroke, and rehabilitative therapies. Here, the hypothesis is tested that lesion location influences the activation patterns. Using functional magnetic resonance imaging, the objective was to characterize similarities or differences in movement-related activation patterns in patients chronically disabled by cortical plus subcortical or subcortical lesions only. Brain activation was mapped during paretic and non-paretic movement in 11 patients with subcortical stroke, in nine patients with stroke involving sensorimotor cortex, and in eight healthy volunteers. Patient groups had similar average motor deficit as measured by a battery of scores and strength measures. Substantial differences between patients groups were found in activation patterns associated with paretic limb movement: whereas contralateral motor cortex, ipsilateral cerebellum (relative to moving limb), bilateral mesial (cingulate, SMA), and perisylvian regions were active in subcortical stroke, cortical patients recruited only ipsilateral postcentral mesial hemisphere regions, and areas at the rim of the stroke cavity. For both groups, activation in ipsilateral postcentral cortex correlated with motor function; in subcortical stroke, the same was found for mesial and perisylvian regions. Overall, brain activation in cortical stroke was less, while in subcortical patients, more than in healthy controls. For non-paretic movement, activation patterns were similar to control in cortical patients. In subcortical patients, however, activation patterns differed: the activation of non-paretic movement was similar to that of paretic movement (corrected for side). The data demonstrate more differences than similarities in the central control of paretic and non-paretic limb movement in patients chronically disabled by subcortical versus cortical stroke. Whereas standard motor circuitry is utilized in subcortical stroke, alternative networks are recruited after cortical stroke. This finding proposes lesion-specific mechanisms of reorganization. Optimal activation of these distinct networks may require different rehabilitative strategies.

Background: Previous studies comparing paretic limb blood flow with the unaffected limb have been contradictory and have often omitted comparisons of peak reactive hyperemic flow. Our objective was to perform bilateral measurements of resting and reactive hyperemic blood flow in the lower legs of chronic (>6 months) stroke patients. A secondary purpose was to determine the extent to which any unilateral changes in limb blood flow were a function of decreases in lean tissue mass on the affected side. We hypothesized that the chronic hemiparesis accompanying ischemic stroke creates an altered metabolic environment in the tissues of the affected side that ultimately impairs vasomotor function., Methods: The study used a single-visit cross-sectional design. All tests were performed at the Baltimore VA Medical Center. Nineteen chronic hemiparetic stroke patients (15 male, 4 female) who had mild to moderate hemiparetic gait after ischemic stroke were recruited for observation. Bilateral measurements of resting and reactive hyperemic blood flow were made using venous occlusion strain gauge plethysmography. Paired t-tests were used for the between leg comparison. Regression analysis and analysis of covariance were utilized to determine the strength of the relationship between lower leg lean tissue mass and blood flow., Results: Resting and reactive hyperemic blood flows were significantly reduced in the paretic compared with the non-paretic limb (32 and 35%, respectively, p < 0.001). Lean tissue mass was also significantly lower in the affected limb (p < 0.01). However, neither resting nor reactive hyperemic blood flows were significantly correlated with lower leg lean tissue mass by dual energy X-ray absorptiometry. The difference in blood flow between limbs remained after covarying for lean tissue mass., Conclusion: Hemiparesis causes impairments in vasomotor function under both resting and hyperemic conditions that are independent of the muscle atrophy on the affected side.

Background and Purpose: Although acquired immunodeficiency syndrome (AIDS) is thought to increase the risk of stroke, few data exist to quantify this risk. This is the first population-based study to quantify the AIDS-associated risk of stroke., Methods: We identified all incident ischemic stroke (IS) and intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in central Maryland and Washington, DC, who were discharged from any of the 46 hospitals in the study area in 1988 and 1991. Using data from the medical records, 2 neurologists reviewed each case to confirm the diagnosis. Cases of AIDS among these patients with stroke were defined using Centers for Disease Control and Prevention criteria (1987). The number of cases of AIDS in the central Maryland and Washington population during 1988 and 1991 was determined from regional health departments working with the Centers for Disease Control and Prevention. Poisson regression was used to estimate the age-, race-, and sex-adjusted relative risk of stroke associated with AIDS., Results: There were 385 IS cases (6 with AIDS) and 171 ICH cases (6 with AIDS). The incidences of IS and ICH among persons with AIDS were both 0.2% per year. AIDS conferred an adjusted relative risk of 13.7 (95% confidence interval [CI], 6.1 to 30.8) for IS and 25.5 (95% CI, 11.2 to 58.0) for ICH. After exclusion of 5 cases of stroke in AIDS patients in whom other potential causes were identified, AIDS patients continued to have an increased risk of stroke with an adjusted relative risk of 9.1 (95% CI, 3.4 to 24.6) for IS and 12.7 (95% CI, 4.0 to 40.0) for ICH., Conclusions: This population-based study found that AIDS is strongly associated with both IS and ICH.

Objective: To assess the test-retest reliability of cardiopulmonary measurements during peak effort and submaximal treadmill walking tests in older patients with gait-impaired chronic hemiparetic stroke., Design: Nonrandomized test-retest., Setting: Hospital geriatric research stress testing laboratory., Participants: Fifty-three subjects (44 men, 9 women; mean age, 65+/-8y) with chronic hemiparetic gait after remote (>6mo) ischemic stroke. Patients had mild to moderate chronic hemiparetic gait deficits, making handrail support necessary during treadmill walking., Interventions: Peak effort and submaximal effort treadmill walking tests were conducted and then repeated on a separate day at least a week later. Main outcome measures Reliability coefficients (r) were calculated for heart rate, systolic blood pressure (SBP), oxygen consumption (Vo(2) [L/min]), Vo(2) (mL.kg(-1).min(-1)), respiratory exchange ratio (RER), rate-pressure product (RPP), and oxygen pulse during peak effort testing. The reliability coefficients for all but SBP and RPP data were calculated from the submaximal tests., Results: Heart rate (r=.87), Vo(2)peak (L/min) (r=.92), Vo(2)peak (mL.kg(-1).min(-1)) (r=.92), and oxygen pulse (r=93) were highly reliable parameters during maximal testing in this population. Submaximal testing produced highly reliable results for V.o(2) (L/min) (r=.89) and oxygen pulse (r=.85). All cardiopulmonary measures except RER had a reliability coefficient greater than.80 during submaximal testing in this population., Conclusion: Our study provides the first evidence that peak effort treadmill testing provides highly reliable oxygen consumption measures in chronic hemiparetic stroke patients using minimal handrail support. The submaximal tests were at or near the threshold level of reliability for the 2 most important measures of V.o(2) (L/min) and V.o(2) (mL.kg(-1).min(-1)) (r=.89, r=.84, respectively), with the remaining measures falling above.70.

Objective: To determine whether circulating concentrations of the counteradhesive proteins SPARC (secreted protein acidic and rich in cysteine) and thrombospondin-1 (TSP-1) are elevated in scleroderma (systemic sclerosis, SSc). The relationship of these counteradhesive proteins to measures of platelet and endothelial cell activation was examined., Methods: Plasma from 45 patients with SSc (26 limited form, 19 diffuse) and 22 age and sex matched controls was assayed for SPARC, TSP-1, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4), 2 distinct platelet a-granule products, and soluble E-selectin, a marker of endothelial cell activation., Results: The mean (+/- SE) SPARC concentration was greater in patients with limited SSc (124.0 +/- 9.6 ng/ml) compared to controls (66.8 +/- 8.0 ng/ml) (p = 0.0005), whereas in patients with diffuse SSc (74.1 +/- 7.9 ng/ml) it was not. Elevated SPARC concentrations in the limited SSc group could not be ascribed to either platelet or endothelial cell activation. TSP-1 concentrations were also increased in SSc patients (n = 29) compared to controls (n = 11) (2.98 +/- 0.12 vs 2.4 +/- 0.21 log transformed ng/ml; p < 0.02). Unlike SPARC, TSP-1 concentrations correlated with both betaTG (r = 0.57, p = 0.0014) and PF4 (r = 0.41, p = 0.026) levels, indicating that increased TSP-1 could, in part, be explained through elevated platelet a-granule release in SSc patients. Plasma levels of betaTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls., Conclusion: That circulating SPARC and TSP-1 are elevated in patients with SSc raises the possibility that counteradhesive proteins, which regulate vascular organization and remodeling, might contribute to the pathogenesis of SSc vasculopathy.