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Biomedical subjects

Richard F Macko

Publications and source records attributed to Richard F Macko.

At least 19 recordsLinked to original sources

Determinants of walking function after stroke: differences by deficit severity.

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.

Adult↗

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

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

Aged↗

Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. METHODS: Tissue plasminogen activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. RESULTS: TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (P<0.0001 for interaction effects between time and treatment). At 24 hours, higher levels of tPA antigen were associated with a lower chance of favorable outcome (odds ratio [OR]=0.34; 95% CI, 0.14 to 0.82) selectively in the rtPA group, and higher levels of TAT (OR=1.72; 95% CI, 1.26 to 2.34) in the entire cohort and of thrombomodulin selectively in the rtPA group (OR=4.45; 95% CI, 1.26 to 15.67) were associated with higher 3-month mortality. CONCLUSIONS: Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis.

Acute Disease↗

Effects of treadmill exercise on transcranial magnetic stimulation-induced excitability to quadriceps after stroke.

OBJECTIVE: To determine characteristics of transcranial magnetic stimulation (TMS)-induced measures of central motor excitability to the paretic and nonparetic quadriceps muscles of chronic hemiparetic stroke patients in the context of a short-term, submaximal bout treadmill exercise. DESIGN: Cross-sectional. SETTING: Motor control and gait biomechanics laboratory. PARTICIPANTS: Convenience sample of 11 patients including cohorts of treadmill untrained (n=8) and trained (n=3) stroke patients with chronic hemiparetic gait. INTERVENTION: Short-term submaximal treadmill exercise. MAIN OUTCOME MEASURES: Thresholds, amplitudes and latencies of TMS-induced motor evoked potentials at vastus medialis in paretic and nonparetic lower extremities. RESULTS: Baseline characteristics of the motor evoked potentials (MEPs) show significantly higher motor thresholds, longer latencies, and reduced amplitudes on the paretic side. In cross-sectional comparisons a group of treadmill-trained patients had greater paretic MEP amplitude changes after treadmill exercise versus paretic MEP responses from a group of untrained patients. CONCLUSIONS: These results indicate that treadmill training for 3 months or more may alter responsiveness of the lower-extremity central motor pathways to a short-term treadmill stimulus.

Aged↗

Exercise rehabilitation after 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.

Adaptation, Physiological↗

Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: a randomized, controlled trial.

BACKGROUND AND PURPOSE: Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. METHODS: Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. RESULTS: Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, delta% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. CONCLUSIONS: T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Aged↗

Human gender differences in fibrinolytic responses to exercise training and their determinants.

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.

Aged↗

Elevated tumor necrosis factor-alpha in skeletal muscle after stroke.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine negligibly expressed in normal muscle, is elevated in selected metabolic conditions characterized by muscle wasting and insulin resistance. Inflammation is fundamental to stroke pathogenesis. Stroke patients have gross muscular atrophy and high prevalence of diabetes and insulin resistance. Yet, no previous studies examined TNF-alpha expression in hemiparetic skeletal muscle. This study investigates whether TNF-alpha mRNA levels are elevated in paretic compared with nonparetic leg muscles of chronic ischemic stroke patients and age-matched controls. METHOD: Total RNA extracted from bilateral vastus lateralis muscle biopsies from n=20 hemiparetic stroke patients and n=9 healthy controls was reverse transcribed to cDNA, then TNF-alpha transcripts were amplified by real-time quantitative polymerase chain reaction. TNF-alpha mRNA concentrations were normalized against acidic ribosomal phosphoprotein, housekeeping gene. RESULTS: TNF-alpha mRNA levels were 2.8-fold higher in paretic compared with control leg muscle (6.28+/-1.86 versus 2.28+/-0.67; P<0.03) and 1.6-fold higher in nonparetic leg (3.71+/-1.02; P<0.11) compared with controls. There was a trend for higher TNF-alpha mRNA in paretic compared with nonparetic leg. CONCLUSIONS: Findings demonstrate increased TNF-alpha expression in paretic leg muscle, suggesting inflammatory pathways are accelerated in stroke muscle. Further studies are under way to determine whether intramuscular TNF-alpha contributes to atrophy and metabolic abnormalities after stroke.

Aged↗

Promoter polymorphisms in the nitric oxide synthase 3 gene are associated with ischemic stroke susceptibility in young black women.

BACKGROUND AND PURPOSE: Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility. METHODS: We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4. RESULTS: Significant associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D'=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective. CONCLUSIONS: Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women.

Adolescent↗

Brain activation of lower extremity movement in chronically impaired 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.

Aged↗

Steps after stroke: capturing ambulatory recovery.

BACKGROUND AND PURPOSE: Nearly two thirds of stroke survivors have deficits impairing ambulatory recovery. Conventional mobility outcome measures such as timed walks and functional independence measure (FIM) do not quantify free-living ambulatory behavior. This study compared step activity monitoring (SAM) with established instruments to assess ambulatory recovery across the outpatient subacute stroke rehabilitation phase. METHODS: We measured FIM mobility subscale, SAM-derived daily steps, Stroke Impact Scale (SIS) mobility scores, and timed walks in 11 subjects after discharge from inpatient rehabilitation and again 3 months later. RESULTS: Significant improvement was measured in free-living step activity (mean gain 80%; P=0.001) but not with timed walks (P=0.4), FIM (P=0.08), or SIS mobility scales (P=0.3). CONCLUSIONS: Microprocessor-linked SAM is a sensitive indicator of ambulatory recovery that measures improvements not captured by other conventional outcome instruments.

Activities of Daily Living↗

Reduced ambulatory activity after stroke: the role of balance, gait, and cardiovascular fitness.

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.

Aged↗

Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study.

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.

Adolescent↗

Unilateral impairment of leg blood flow in chronic stroke patients.

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.

Absorptiometry, Photon↗

Muscle molecular phenotype after stroke is associated with gait speed.

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

Aged↗

Accelerometer monitoring of home- and community-based ambulatory activity after stroke.

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.

Activities of Daily Living↗

Exercise training enhances endogenous fibrinolysis in peripheral arterial disease.

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.

Aged↗

Lesion location alters brain activation in chronically impaired stroke survivors.

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.

Aged↗