Peter Langhorne

Motor recovery after stroke: a systematic review

Loss of functional movement is a common consequence of stroke for which a wide range of interventions has been developed. In this Review, we aimed to provide an overview of the available evidence on interventions for motor recovery after stroke through the evaluation of systematic reviews, supplemented by recent randomised controlled trials. Most trials were small and had some design limitations. Improvements in recovery of arm function were seen for constraint-induced movement therapy, electromyographic biofeedback, mental practice with motor imagery, and robotics. Improvements in transfer ability or balance were seen with repetitive task training, biofeedback, and training with a moving platform. Physical fitness training, high-intensity therapy (usually physiotherapy), and repetitive task training improved walking speed. Although the existing evidence is limited by poor trial designs, some treatments do show promise for improving motor recovery, particularly those that have focused on high-intensity and repetitive task-specific practice.

Effects of Augmented Exercise Therapy Time After Stroke A Meta-Analysis

Background and Purpose— To present a systematic review of studies that addresses the effects of intensity of augmented exercise therapy time (AETT) on activities of daily living (ADL), walking, and dexterity in patients with stroke. Summary of Review— A database of articles published from 1966 to November 2003 was compiled from MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, PEDro, DARE, and PiCarta using combinations of the following key words: stroke, cerebrovascular disorders, physical therapy, physiotherapy, occupational therapy, exercise therapy, rehabilitation, intensity, dose–response relationship, effectiveness, and randomized controlled trial. References presented in relevant publications were examined as well as abstracts in proceedings. Studies that satisfied the following selection criteria were included: (1) patients had a diagnosis of stroke; (2) effects of intensity of exercise training were investigated; and (3) design of the study was a randomized controlled trial (RCT). For each outcome measure, the estimated effect size (ES) and the summary effect size (SES) expressed in standard deviation units (SDU) were calculated for ADL, walking speed, and dexterity using fixed and random effect models. Correlation coefficients were calculated between observed individual effect sizes on ADL of each study, additional time spent on exercise training, and methodological quality. Cumulative meta-analyses (random effects model) adjusted for the difference in treatment intensity in each study was used for the trials evaluating the effects of AETT provided. Twenty of the 31 candidate studies, involving 2686 stroke patients, were included in the synthesis. The methodological quality ranged from 2 to 10 out of the maximum score of 14 points. The meta-analysis resulted in a small but statistically significant SES with regard to ADL measured at the end of the intervention phase. Further analysis showed a significant homogeneous SES for 17 studies that investigated effects of increased exercise intensity within the first 6 months after stroke. No significant SES was observed for the 3 studies conducted in the chronic phase. Cumulative meta-analysis strongly suggests that at least a 16-hour difference in treatment time between experimental and control groups provided in the first 6 months after stroke is needed to obtain significant differences in ADL. A significant SES supporting a higher intensity was also observed for instrumental ADL and walking speed, whereas no significant SES was found for dexterity. Conclusion— The results of the present research synthesis support the hypothesis that augmented exercise therapy has a small but favorable effect on ADL, particularly if therapy input is augmented at least 16 hours within the first 6 months after stroke. This meta-analysis also suggests that clinically relevant treatment effects may be achieved on instrumental ADL and gait speed.

Stroke Care 2 Stroke rehabilitation

Stroke is a common, serious, and disabling global health-care problem, and rehabilitation is a major part of patient care. There is evidence to support rehabilitation in well coordinated multidisciplinary stroke units or through provision of early supported provision of discharge teams. Potentially beneficial treatment options for motor recovery of the arm include constraint-induced movement therapy and robotics. Promising interventions that could be beneficial to improve aspects of gait include fitness training, high-intensity therapy, and repetitive-task training. Repetitive-task training might also improve transfer functions. Occupational therapy can improve activities of daily living; however, information about the clinical effect of various strategies of cognitive rehabilitation and strategies for aphasia and dysarthria is scarce. Several large trials of rehabilitation practice and of novel therapies (eg, stem-cell therapy, repetitive transcranial magnetic stimulation, virtual reality, robotic therapies, and drug augmentation) are underway to inform future practice.

Thrombophilia in pregnancy: a systematic review

Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0·74–34·40); early pregnancy loss (ORs, 1·40–6·25); late pregnancy loss (ORs, 1·31–20·09); pre‐eclampsia (ORs, 1·37–3·49); placental abruption (ORs, 1·42–7·71) and intrauterine growth restriction (ORs, 1·24–2·92). Low‐dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1·62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials

Objective To evaluate the effectiveness of comprehensive geriatric assessment in hospital for older adults admitted as an emergency. Search strategy We searched the EPOC Register, Cochrane’s Controlled Trials Register, the Database of Abstracts of Reviews of Effects (DARE), Medline, Embase, CINAHL, AARP Ageline, and handsearched high yield journals. Selection criteria Randomised controlled trials of comprehensive geriatric assessment (whether by mobile teams or in designated wards) compared with usual care. Comprehensive geriatric assessment is a multidimensional interdisciplinary diagnostic process used to determine the medical, psychological, and functional capabilities of a frail elderly person to develop a coordinated and integrated plan for treatment and long term follow-up. Data collection and analysis Three independent reviewers assessed eligibility and trial quality and extracted published data. Two additional reviewers moderated. Results Twenty two trials evaluating 10 315 participants in six countries were identified. For the primary outcome “living at home,” patients who underwent comprehensive geriatric assessment were more likely to be alive and in their own homes at the end of scheduled follow-up (odds ratio 1.16 (95% confidence interval 1.05 to 1.28; P=0.003; number needed to treat 33) at a median follow-up of 12 months versus 1.25 (1.11 to 1.42; P<0.001; number needed to treat 17) at a median follow-up of six months) compared with patients who received general medical care. In addition, patients were less likely to be living in residential care (0.78, 0.69 to 0.88; P<0.001). Subgroup interaction suggested differences between the subgroups “wards” and “teams” in favour of wards. Patients were also less likely to die or experience deterioration (0.76, 0.64 to 0.90; P=0.001) and were more likely to experience improved cognition (standardised mean difference 0.08, 0.01 to 0.15; P=0.02) in the comprehensive geriatric assessment group. Conclusions Comprehensive geriatric assessment increases patients’ likelihood of being alive and in their own homes after an emergency admission to hospital. This seems to be especially true for trials of wards designated for comprehensive geriatric assessment and is associated with a potential cost reduction compared with general medical care.

Do stroke units save lives

Management of stroke patients in specialist stroke units hastens recovery but is not believed to influence mortality. We did a statistical overview of randomised controlled trials reported between 1962 and 1993 in which the management of stroke patients in a specialist unit was compared with that in general wards. We identified 10 trials, 8 of which used a strict randomisation procedure. 1586 stroke patients were included; 766 were allocated to a stroke unit and 820 to general wards. The odds ratio (stroke unit vs general wards) for mortality within the first 4 months (median follow-up 3 months) after the stroke was 0.72 (95% CI 0.56-0.92), consistent with a reduction in mortality of 28% (2p < 0.01). This reduction persisted (odds ratio 0.79, 95% CI 0.63-0.99, 2p < 0.05) when calculated for mortality during the first 12 months. The findings were not significantly altered if the analysis was limited to studies that used a formal randomisation procedure. We conclude that management of stroke patients in a stroke unit is associated with a sustained reduction in mortality.

Association of gait and balance disorders with age-related white matter changes The LADIS Study

Objective: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on different objective measures of gait and balance. Methods: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading. Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. Results: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB: 10.2 ± 2.1 in the mild, 9.9 ± 2.0 in the moderate, 8.9 ± 2.6 in the severe group; p < 0.001). Walking speed correlated with the severity of ARWMC (1.24 ± 0.28 m/second in the mild, 1.18 ± 0.32 m/second in the moderate, and 1.09 ± 0.31 m/second in the severe group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg stance time: 18.9 ± 10.8 seconds) compared with moderate and severe ARWMC (16.4 ± 10.8 and 13.6 ± 11.2 seconds) (p < 0.001). Physically inactive individuals had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). Conclusions: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes. Design Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints. Setting 11 European centres. Participants 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy. Main outcome measure Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score ≥2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke. Results Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect. Conclusion The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

BACKGROUND Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Early supported discharge services for stroke patients: a meta-analysis of individual patients' data

BACKGROUND Stroke patients conventionally undergo a substantial part of their rehabilitation in hospital. Services have been developed that offer patients early discharge from hospital with rehabilitation at home (early supported discharge [ESD]). We have assessed the effects and costs of such services. METHODS We did a meta-analysis of data from individual patients who took part in randomised trials that recruited patients with stroke in hospital to receive either conventional care or any ESD service intervention that provided rehabilitation and support in a community setting with the aim of shortening the duration of hospital care. The primary outcome was death or dependency at the end of scheduled follow-up. FINDINGS Outcome data were available for 11 trials (1597 patients). ESD services were mostly provided by specialist multidisciplinary teams to a selected group (median 41%) of stroke patients admitted to hospital. There was a reduced risk of death or dependency equivalent to six (95% CI one to ten) fewer adverse outcomes for every 100 patients receiving an ESD service (p=0.02). The hospital stay was 8 days shorter for patients assigned ESD services than for those assigned conventional care (p<0.0001). There were also significant improvements in scores on the extended activities of daily living scale and in the odds of living at home and reporting satisfaction with services. The greatest benefits were seen in the trials evaluating a coordinated multidisciplinary ESD team and in stroke patients with mild to moderate disability. INTERPRETATION Appropriately resourced ESD services provided for a selected group of stroke patients can reduce long-term dependency and admission to institutional care as well as shortening hospital stays.