Evaluating Test-Retest Reliability of Fatigability in Chronic Stroke.

OBJECTIVES: The subjective nature of fatigue may contribute to inconsistencies in prevalence rates for post-stroke fatigue. More objective performance fatigue measures may offer a more reliable construct of fatigue. Our goal was to establish test-retest reliability of fatigability in stroke during 6-minute walk (6MW) testing. Relationships between post-stoke fatigability and other constructs were assessed. MATERIALS AND METHODS: Twenty-three hemiparetic stroke survivors underwent two 6MW tests with portable metabolic monitoring performed at least 48 hours apart. Fatigability was defined as ratio of change in walking speed to distance covered during the 6MW. 6MW oxygen consumption (VO2), peak aerobic capacity (VO2peak), walking speed over-ground, dynamic gait index, fatigue, falls efficacy, and BMI were measured. RESULTS: Fatigability was highly correlated between both 6MW trials (ICC = 0.99, p < 0.001) with no significant difference between trials (0.08, p = 0.48). The strongest correlation was between fatigability and 6MW VO2 trial 1 and 2 (r = 0.92, p < 0.001 and r = 0.95, p < 0.001, respectively). Moderate-to-strong relationships were observed between fatigability for 6MW and fastest-comfortable walking speed (r = -0.82 and -0.77), self-selected walking speed (r = -7.8 and -0.78), 6MW walking speed (r = -0.80 and 0.80, VO2peak (r = -0.47 and -0.48) (p < 0.001), and DGI (r = -0.70 and -0.68, p < 0.001). CONCLUSION: This study establishes test-retest reliability for an objective measure of fatigue in stroke-related disability. The strong correlations between fatigability and other functional measures also provides insight into the contributors underlying fatigability in this population. REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01322607.

CD31+ Circulating Angiogenic Cell Number and Subtypes are Reduced in Individuals with Chronic Stroke.

BACKGROUND AND PURPOSE: Reduced number and function of CD31+ circulating angiogenic cells (CACs) may explain vascular complications associated with the chronic phase stroke. The purpose of this study was to quantify CD31+ CAC paracrine function, total number and number of various subtypes of CD31+ CACs in individuals with chronic stroke compared with controls. METHODS: Peripheral blood mononuclear cells were isolated from chronic stroke participants and controls. CD31+ cells were quantified by flow cytometry, as was co-expression of CD31 in combination with CD14, CD3, CD11b, or CD34. Immunomagnetically selected CD31+ cells were cultured, and conditioned medium was used in a capillary-like network assay. RESULTS: Significantly lower levels of CD31+ CACs were found in stroke participants compared with controls (-24%; P=0.04). Additionally, CD31+/CD14+, CD31+/CD11b+ and CD31+/CD3+ cells were significantly lower in the chronic stroke group compared with controls (-45%, P=0.02; -47%, P=0.02 and -32%, P=0.03, respectively). There was no group effect on CD31+ CAC conditioned media-mediated capillary-like network formation. CONCLUSION: CD31+ CACs and subtypes may serve as potential therapeutic targets in chronic stroke recovery.

Brain-derived neurotrophic factor, epigenetics in stroke skeletal muscle, and exercise training.

OBJECTIVE: (1) To compare paretic (P) vs nonparetic (NP) skeletal muscle brain-derived neurotrophic factor (BDNF) and the effects of resistive training (RT) on systemic and skeletal muscle BDNF mRNA expression in stroke; and (2) to compare the DNA methylation profile for BDNF and BDNFAS (BDNF antisense RNA) between P and NP muscle and the effects of aerobic exercise training (AEX) on DNA methylation in stroke. METHODS: In this longitudinal investigation, participants (50-76 years) with chronic stroke underwent a fasting blood draw, a 12-week (3×/week) RT intervention (n = 16), and repeated bilateral vastus lateralis muscle tissue biopsies (n = 10) with BDNF expression determined by RT-PCR. Five stroke survivors completed 6 months of AEX (3×/week) and had bilateral muscle biopsies. DNA methylation status in gene BDNF and BDNFAS was assessed by Illumina 450k methylation array. RESULTS: P muscle had ∼45% lower BDNF mRNA expression than NP muscle (6.79 ± 1.30 vs 10.52 ± 2.06 arbitrary units [AU], p < 0.05), and P muscle exhibited differential methylation status in the DNA sequences of BDNF (3 CpG [5'-C-phosphate-G-3'] sites, p = 0.016-0.044) and BDNFAS (1 CpG site, p = 0.016) compared to NP. Plasma BDNF and muscle BDNF messenger RNA (mRNA) expression did not significantly change after RT. BDNFAS DNA methylation increased after AEX in P relative to NP muscle (p = 0.017). CONCLUSIONS: This is the first evidence that stroke hemiparesis reduces BDNF skeletal muscle expression, with our findings identifying methylation alterations on the DNA sequence of BDNF and BDNFAS gene. Preliminary results further indicate that AEX increases methylation in BDNFAS gene, which presumably could regulate the expression of BDNF.

Validating accelerometry as a measure of physical activity and energy expenditure in chronic stroke.

BACKGROUND: Accelerometers can objectively measure steps taken per day in individuals without gait deficits, but accelerometers also have the ability to estimate frequency, intensity, and duration of physical activity. However, thresholds to distinguish varying levels of activity intensity using the Actical brand accelerometer are standardized only for the general population and may underestimate intensity in stroke. OBJECTIVE: To derive Actical activity count thresholds specific to stroke disability for use in more accurately gauging time spent at differing activity levels. METHODS: Men (n = 18) and women (n = 10) with chronic hemiparetic gait (4 ± 2 years latency, 43% Caucasian, 56% African-American, ages of 47-83 years, BMI 19-48 kg/m2) participated in the study. Actical accelerometers were placed on the non-paretic hip to obtain accelerometry counts during eight activities of varying intensity: (1) watching TV; (2) seated stretching; (3) standing stretching; (4) floor sweeping; (5) stepping in place; (6) over-ground walking; (7) lower speed treadmill walking (1.0 mph at 4% incline); and (8) higher speed treadmill walking (2.0 mph at 4% incline). Simultaneous portable monitoring (Cosmed K4b2) enabled quantification of energy cost for each activity in metabolic equivalents (METs, or oxygen consumption in multiples of resting level). Measurements were obtained for 10 min of standard rest and 5 min during each of the eight activities. RESULTS: Regression analysis yielded the following new stroke-specific Actical minimum thresholds: 125 counts per minute (cpm) for sedentary/light activity, 667 cpm for light/moderate activity, and 1546 cpm for moderate/vigorous activity. CONCLUSION: Our revised cut points better reflect activity levels after stroke and suggest significantly lower thresholds relative to those observed for the general population of healthy individuals. We conclude that the standard, commonly applied Actical thresholds are inappropriate for this unique population.

Resistive Training and Molecular Regulators of Vascular-Metabolic Risk in Chronic Stroke.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC-1α) gene and Sirtuin-1 (SIRT-1) respond to physiological stimuli and regulate insulin resistance. Inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and the soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1) are associated with increased risk of diabetes and coronary heart disease. Resistive training (RT) reduces hyperinsulinemia and improves insulin action in chronic stroke. Yet, the molecular mechanisms for this are unknown. This study will determine the effects of RT on skeletal muscle PGC-1α and SIRT-1 mRNA expression and inflammatory and vascular markers. METHODS: Stroke survivors (50-76 years) underwent a fasting blood draw for measurement of TNF-α, IL-6, CRP, serum amyloid A, sICAM-1, sVCAM-1, and bilateral vastus lateralis biopsies before and after RT. Participants were also assessed using bilateral multislice thigh computed tomography scans from the knee to the hip, a total body scan by dual-energy X-ray absorptiometry, and 1-repetition maximum strength testing. Subjects performed 2 sets of 3 lower extremity RT exercises 3 times per week for 12 weeks. RESULTS: Bilateral leg press and leg extension strength increased ~30-50% with RT (P < .001). Body weight, total body fat mass, and fat-free mass did not change. Thigh muscle area and volume increased in both legs (P < .05). Nonparetic muscle PGC-1α mRNA expression increased 14% (P < .05) after RT and SIRT-1 mRNA decreased 24% (P < .05) and 31% (P < .01) in paretic and nonparetic muscles. There were no significant changes in plasma inflammation with training. DISCUSSION: RT in chronic stroke induces changes in key skeletal muscle regulators of metabolism, without effecting circulating inflammation.

Sarcopenia and Physical Function in Middle-Aged and Older Stroke Survivors.

OBJECTIVES: To determine the prevalence of sarcopenia in stroke survivors using different methodologies, and compare a subset of the stroke group to age-, sex-, and body mass index (BMI)-matched nonstroke control counterparts. DESIGN: Cohort study. SETTING: A Veterans Affairs medical center and a university hospital. PARTICIPANTS: Mild to moderately disabled participants >6 months after onset of stroke aged 40 to 84 years (N=190, 61% men, 57% African American; mean BMI ± SEM, 29±1kg/m2). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry scans to assess appendicular lean mass (ALM). Rates of sarcopenia were determined using 4 established methods: (1) ALM/height2 (ALM/ht2); (2) European Working Group on Sarcopenia in Older Persons; (3) International Working Group on Sarcopenia; and (4) ALM/BMI. RESULTS: Sarcopenia prevalence in our stroke cohort ranged between 14% and 18%. The stroke survivor subset (n=38) matched one-for-one with control counterparts for race, sex, age ±4 years and BMI ±2.5kg/m2 had higher prevalence rates compared with their nonstroke counterparts (13.2% vs 5.3%, P<.0001). ALM/ht2 was related to 6-minute walking speed (r=.28, P<.01) and peak oxygen consumption (L/min: r=.58, P<.0001) for the stroke group. CONCLUSIONS: Stroke survivors show an elevated prevalence of sarcopenia when considering age, sex, and race compared with nonstroke individuals.

Strength Training for Skeletal Muscle Endurance after Stroke.

BACKGROUND AND PURPOSE: Initial studies support the use of strength training (ST) as a safe and effective intervention after stroke. Our previous work shows that relatively aggressive, higher intensity ST translates into large effect sizes for paretic and non-paretic leg muscle volume, myostatin expression, and maximum strength post-stroke. An unanswered question pertains to how our unique ST model for stroke impacts skeletal muscle endurance (SME). Thus, we now report on ST-induced adaptation in the ability to sustain isotonic muscle contraction. METHODS: Following screening and baseline testing, hemiparetic stroke participants were randomized to either ST or an attention-matched stretch control group (SC). Those in the ST group trained each leg individually to muscle failure (20 repetition sets, 3× per week for 3 months) on each of three pneumatic resistance machines (leg press, leg extension, and leg curl). Our primary outcome measure was SME, quantified as the number of submaximal weight leg press repetitions possible at a specified cadence. The secondary measures included one-repetition maximum strength, 6-minute walk distance (6MWD), 10-meter walk speeds, and peak aerobic capacity (VO2 peak). RESULTS: ST participants (N = 14) had significantly greater SME gains compared with SC participants (N = 16) in both the paretic (178% versus 12%, P < .01) and non-paretic legs (161% versus 12%, P < .01). These gains were accompanied by group differences for 6MWD (P < .05) and VO2 peak (P < .05). CONCLUSION: Our ST regimen had a large impact on the capacity to sustain submaximal muscle contraction, a metric that may carry more practical significance for stroke than the often reported measures of maximum strength.

Robotically assisted treadmill exercise training for improving peak fitness in chronic motor incomplete spinal cord injury: A randomized controlled trial.

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.

Higher Treadmill Training Intensity to Address Functional Aerobic Impairment after Stroke.

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.

Impact of serum nutritional status on physical function in african american and caucasian stroke survivors.

Background. The purpose of this study is to compare serum nutritional profiles in chronic stroke survivors to a representative sample of US Adults (NHANESIII) and determine whether these serum markers differed by race and impact physical function in stroke. Methods. Fasting serum samples were collected for analysis of lipids, uric acid, and albumin in 145 African American (AA) and 111 Caucasian (C) stroke survivors (age: 60 ± 1 years [mean ± SEM]). A six-minute walk was performed in a subset of stroke survivors (N = 134). Results. Triglycerides were higher and HDL-cholesterol and albumin lower in C than AA women stroke survivors (Ps < 0.05). Uric acid was lower in C than AA stroke survivors (P < 0.05). Compared to NHANESIII, HDL-cholesterol, albumin, and hemoglobin generally were lower (Ps < 0.05) and lipids were more favorable in stroke (Ps < 0.01). Uric acid was related to six-minute walk performance among a subset of stroke survivors (P < 0.05). Conclusion. In stroke, racial differences exist with regard to serum nutritional risk, but these differences are similar to that observed in the general population. Regardless of race, nutritional risk appears elevated above that of the general population with regard to many of the serum markers. As a modifiable biomarker, uric acid should be monitored closely as it may provide insight into the functional risk of stroke survivors.

Resistive training improves insulin sensitivity after stroke.

BACKGROUND: Insulin resistance is highly prevalent after stroke, contributing to comorbid cardiovascular conditions that are the leading cause of death in the stroke population. This study determined the effects of unilateral resistive training (RT) of both the paretic and nonparetic legs on insulin sensitivity in stroke survivors. METHODS: We studied 10 participants (mean age 65 ± 2 years; mean body mass index 27 ± 4 kg/m2) with hemiparetic gait after remote (>6 months) ischemic stroke. All subjects underwent 1-repetition maximum (1-RM) strength testing, 9 had an oral glucose tolerance test (OGTT), and 7 completed a 2-hour hyperglycemic clamp (with glucose elevation targeted at 98 mg/dL above baseline fasting level) before and after 12 weeks (3×/week) of progressive, high repetition, high-intensity RT. Body composition was assessed by dual-energy x-ray absorbtiometry in all participants. RESULTS: Leg press and leg extension 1-RM increased in the paretic leg by 22% (P < .05) and 45% (P < .01), respectively. Fasting insulin decreased 23% (P < .05), with no change in fasting glucose. The 16% reduction in OGTT insulin area under the curve (AUC) across training was not statistically significant (P = .18). There was also no change in glucose AUC. First-phase insulin response during the hyperglycemic clamp (0-10 minutes) decreased 24% (P < .05), and second-phase insulin response (10-120 minutes) decreased 26% (P < .01). Insulin sensitivity increased by 31% after RT according to clamp calculations (P < .05). CONCLUSIONS: These findings provide the first preliminary evidence that RT may reduce hyperinsulinemia and improve insulin sensitivity after disabling stroke.

The short physical performance battery as a predictor of functional capacity after stroke.

BACKGROUND: The short physical performance battery is a widely used instrument for quantifying lower extremity function in older adults. However, its utility for predicting endurance-based measures of functional performance that are more difficult to conduct in clinical settings is unknown. An understanding of this could be particularly relevant in mobility impaired stroke survivors, for whom establishing the predictive strength of simpler to perform measures would aid in tracking broader categories of functional disability. This cross-sectional study was conducted to determine whether the short physical performance battery is related to functional measures with a strong endurance component. METHODS: Functional measures (short physical performance battery, peak aerobic capacity, and 6-minute walk) were obtained and compared for the first time in stroke survivors with hemiparetic gait. Pearson correlation coefficients were used to assess strength of the relationships (α P < .05). RESULTS: Forty-three stroke participants performed a standardized short physical performance battery. Forty-one of the subjects completed a 6-minute walk, and 40 completed a peak treadmill test. Mean short physical performance battery (6.3 ± 2.5 [mean ± SD]), 6-minute walk (242 ± 115 meters), and peak aerobic capacity (17.4 ± 5.4 mL/kg/min) indicated subjects had moderate to severely impaired lower extremity functional performance. The short physical performance battery was related to both 6-minute walk (r = 0.76; P < .0001) and peak fitness (r = 0.52; P < .001). CONCLUSIONS: Our results show that the short physical performance battery may be reflective of endurance-based, longer-distance performance measures that would be difficult to perform in standard clinical stroke settings. Additional studies are needed to explore the value of using the short physical performance battery to assess rehabilitation-related functional progression after stroke.

Test-retest reliability of portable metabolic monitoring after disabling stroke.

PURPOSE: Impaired economy of gait, prevalent in chronic stroke secondary to residual gait deficits, is associated with intolerance for performing activities of daily living. Gait economy/efficiency is traditionally assessed by determining the rate of oxygen consumption during submaximal treadmill walking. However, the mechanics and energetics of treadmill versus overground walking are very different in stroke survivors with ambulatory deficits. Clearly, overground cardiopulmonary measures are needed to accurately profile movement economy after stroke. An obstacle to obtaining such measures after stroke has been the absence of reliable portable metabolic monitoring equipment. The purpose of this study was to establish the test-retest reliability of a portable metabolic monitoring device during overground walking in hemiparetic stroke survivors. METHODS: Twenty-three chronic hemiparetic stroke survivors underwent two 6-minute walk tests while wearing a COSMED K4b(2) portable metabolic measurement system. Intraclass correlations coefficients (ICC) were calculated for both cardiopulmonary parameters and distance covered to determine test-retest reliability. An ICC of ≥ 0.85 was considered reliable. RESULTS: ICCs for relative Vo2 (0.90), absolute Vo2 (0.93), Vco2 (0.93), and minute ventilation (0.95) demonstrated high reliability, but not for heart rate (0.76) or respiratory exchange ratio (0.64). There was no significant difference in the distance each participant walked between the first and second tests, eliminating distance as a potential confounder of our analyses (ICC = 0.99). CONCLUSIONS: Our results strongly support the reliability of the K4b(2) for quantifying overground gait efficiency after stroke. Use of this device may enable researchers to study how varying poststroke rehabilitation interventions affect this central measure of health and function.

Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease.

OBJECTIVE: To compare the efficacy of treadmill exercises and stretching and resistance exercises in improving gait speed, strength, and fitness for patients with Parkinson disease. DESIGN: A comparative, prospective, randomized, single-blinded clinical trial of 3 types of physical exercise. SETTING: The Parkinson's Disease and Movement Disorders Center at the University of Maryland and the Baltimore Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center. PATIENTS: A total of 67 patients with Parkinson disease who had gait impairment were randomly assigned to 1 of 3 arms of the trial. INTERVENTIONS; (1) A higher-intensity treadmill exercise (30 minutes at 70%-80% of heart rate reserve), (2) a lower-intensity treadmill exercise (50 minutes at 40%-50% of heart rate reserve), and (3) stretching and resistance exercises (2 sets of 10 repetitions on each leg on 3 resistance machines [leg press, leg extension, and curl]). These exercises were performed 3 times a week for 3 months. MAIN OUTCOME MEASURES: The primary outcome measures were gait speed (6-minute walk), cardiovascular fitness (peak oxygen consumption per unit time [$$ VO2], and muscle strength (1-repetition maximum strength). RESULTS: All 3 types of physical exercise improved distance on the 6-minute walk: lower-intensity treadmill exercise (12% increase; P=.001), stretching and resistance exercises (9% increase; P<.02), and higher-intensity treadmill exercise (6% increase; P=.07), with no between-group differences. Both treadmill exercises improved peak $$ VO2 (7%-8% increase; P<.05) more than did the stretching and resistance exercises. Only stretching and resistance improved muscle strength (16% increase; P<.001). CONCLUSIONS: The effects of exercise were seen across all 3 exercise groups. The lower-intensity treadmill exercise resulted in the greatest improvement in gait speed. Both the higher- and lower-intensity treadmill exercises improved cardiovascular fitness. Only the stretching and resistance exercises improved muscle strength. Therefore, exercise can improve gait speed, muscle strength, and fitness for patients with Parkinson disease. The combination of treadmill and resistance exercises may result in greater benefit and requires further investigation.

The Unified Parkinson's Disease Rating Scale as a predictor of peak aerobic capacity and ambulatory function.

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.

Reduced cardiorespiratory fitness after stroke: biological consequences and exercise-induced adaptations.

Evidence from several studies consistently shows decline in cardiorespiratory (CR) fitness and physical function after disabling stroke. The broader implications of such a decline to general health may be partially understood through negative poststroke physiologic adaptations such as unilateral muscle fiber type shifts, impaired hemodynamic function, and decrements in systemic metabolic status. These physiologic changes also interrelate with reductions in activities of daily living (ADLs), community ambulation, and exercise tolerance, causing a perpetual cycle of worsening disability and deteriorating health. Fortunately, initial evidence suggests that stroke participants retain the capacity to adapt physiologically to an exercise training stimulus. However, despite this evidence, exercise as a therapeutic intervention continues to be clinically underutilized in the general stroke population. Far more research is needed to fully comprehend the consequences of and remedies for CR fitness impairments after stroke. The purpose of this brief review is to describe some of what is currently known about the physiological consequences of CR fitness decline after stroke. Additionally, there is an overview of the evidence supporting exercise interventions for improving CR fitness, and associated aspects of general health in this population.

Impaired economy of gait and decreased six-minute walk distance in Parkinson's disease.

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.

Atrophy and intramuscular fat in specific muscles of the thigh: associated weakness and hyperinsulinemia in stroke survivors.

PURPOSE: Sarcopenia and increased fat infiltration in muscle may play a role in the functional impairment and high risk for diabetes in stroke. Our purpose was to compare muscle volume and muscle attenuation across 6 muscles of the paretic and nonparetic thigh and examine the relationships between intramuscular fat and insulin resistance and between muscle volume and strength in stroke patients. METHODS: Stroke participants (70; 39 men, 31 women) aged 40 to 84 years, BMI = 16 to 45 kg/m(2) underwent multiple thigh CT scans, total body scan by DXA (dual-energy X-ray absorptiometry), peak oxygen intake (VO(2peak)) graded treadmill test, 6-minute walk, fasting blood draws, and isokinetic strength testing. RESULTS: Muscle volume is 24% lower and subcutaneous fat volume is 5% higher in the paretic versus nonparetic thigh. Muscle attenuation (index of amount of fat infiltration in muscle) is 17% higher in the nonparetic midthigh than the paretic. The semitendinosis/semimembranosis, biceps femoris, sartorius, vastus (medialis/lateralis), and rectus femoris have lower (between 9% and 19%) muscle areas on the paretic than the nonparetic thigh. Muscle attenuation is 15% to 25% higher on the nonparetic than the paretic side for 5 of 6 muscles. The nonparetic midthigh muscle attenuation is negatively associated with insulin. Eccentric peak torque of the nonparetic leg and paretic leg are associated with the corresponding muscle volume. CONCLUSIONS: The skeletal muscle atrophy, increased fat around and within muscle, and ensuing muscular weakness observed in chronic stroke patients relates to diabetes risk and may impair functional mobility and independence.

Improved cerebral vasomotor reactivity after exercise training in hemiparetic stroke survivors.

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.

Repeatability of aerobic capacity measurements in Parkinson disease.

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.