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Introduction Infection after stroke is associated with unfavorable outcome. Randomized controlled studies did not show benefit of preventive antibiotics in stroke but lacked power for subgroup analyses. Aim of this study is to assess whether preventive antibiotic therapy after stroke improves functional outcome for specific patient groups in an individual patient data meta-analysis. Patients and methods We searched MEDLINE (1946–7 May 2021), Embase (1947–7 May 2021), CENTRAL (17th September 2021), trial registries, cross-checked references and contacted researchers for randomized controlled trials of preventive antibiotic therapy versus placebo or standard care in ischemic or hemorrhagic stroke patients. Meta-analysis was performed by a one-step and two-step approach. Primary outcome was functional outcome adjusted for age and stroke severity. Secondary outcomes were infections and mortality. Results 4197 patients from nine trials were included. Preventive antibiotic therapy was not associated with a shift in functional outcome (mRS) at 3 months (OR1.13, 95%CI 0.98–1.31) or unfavorable functional outcome (mRS 3–6) (OR0.85, 95%CI 0.60–1.19). Preventive antibiotics did not improve functional outcome in pre-defined subgroups (age, stroke severity, timing and type of antibiotic therapy, pneumonia prediction scores, dysphagia, type of stroke, and type of trial). Preventive antibiotics reduced infections (276/2066 (13.4%) in the preventive antibiotic group vs. 417/2059 (20.3%) in the control group, OR 0.60, 95% CI 0.51–0.71, p < 0.001), but not pneumonia (191/2066 (9.2%) in the preventive antibiotic group vs. 205/2061 (9.9%) in the control group (OR 0.92 (0.75–1.14), p = 0.450). Discussion and conclusion Preventive antibiotic therapy did not benefit any subgroup of patients with acute stroke and currently cannot be recommended.

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

PURPOSE: The microbiological aetiology of pneumonia complicating stroke is poorly characterised. In this second Pneumonia in Stroke ConsEnsuS statement, we propose a standardised approach to empirical antibiotic therapy in pneumonia complicating stroke, based on likely microbiological aetiology, to improve antibiotic stewardship. METHODS: Systematic literature searches of multiple databases were undertaken. An evidence review and a round of consensus consultation were completed prior to a final multi-disciplinary consensus meeting in September 2017, held in Barcelona, Spain. Consensus was approached using a modified Delphi technique and defined a priori as 75% agreement between the consensus group members. Findings: No randomised trials to guide antibiotic treatment of pneumonia complicating stroke were identified. Consensus was reached for the following: (1) Stroke-associated pneumonia may be caused by organisms associated with either community-acquired or hospital-acquired pneumonia; (2) Treatment for early stroke-associated pneumonia (

Supplemental Digital Content is available in the text., Background and Purpose— Computed tomography (CT) perfusion (CTP) provides potentially valuable information to guide treatment decisions in acute stroke. Assessment of interobserver reliability of CTP has, however, been limited to small, mostly single center studies. We performed a large, internet-based study to assess observer reliability of CTP interpretation in acute stroke. Methods— We selected 24 cases from the IST-3 (Third International Stroke Trial), ATTEST (Alteplase Versus Tenecteplase for Thrombolysis After Ischaemic Stroke), and POSH (Post Stroke Hyperglycaemia) studies to illustrate various perfusion abnormalities. For each case, observers were presented with noncontrast CT, maps of cerebral blood volume, cerebral blood flow, mean transit time, delay time, and thresholded penumbra maps (dichotomized into penumbra and core), together with a short clinical vignette. Observers used a structured questionnaire to record presence of perfusion deficit, its extent compared with ischemic changes on noncontrast CT, and an Alberta Stroke Program Early CT Score for noncontrast CT and CTP. All images were viewed, and responses were collected online. We assessed observer agreement with Krippendorff-α. Intraobserver agreement was assessed by inviting observers who reviewed all scans for a repeat review of 6 scans. Results— Fifty seven observers contributed to the study, with 27 observers reviewing all 24 scans and 17 observers contributing repeat readings. Interobserver agreement was good to excellent for all CTP. Agreement was higher for perfusion maps compared with noncontrast CT and was higher for mean transit time, delay time, and penumbra map (Krippendorff-α =0.77, 0.79, and 0.81, respectively) compared with cerebral blood volume and cerebral blood flow (Krippendorff-α =0.69 and 0.62, respectively). Intraobserver agreement was fair to substantial in the majority of readers (Krippendorff-α ranged from 0.29 to 0.80). Conclusions— There are high levels of interobserver and intraobserver agreement for the interpretation of CTP in acute stroke, particularly of mean transit time, delay time, and penumbra maps.

Objective To test the hypothesis that supplementary motor area (SMA) facilitation with functional near-infrared spectroscopy–mediated neurofeedback (fNIRS-NFB) augments poststroke gait and balance recovery, we conducted a 2-center, double-blind, randomized controlled trial involving 54 Japanese patients using the 3-meter Timed Up and Go (TUG) test. Methods Patients with subcortical stroke-induced mild to moderate gait disturbance more than 12 weeks from onset underwent 6 sessions of SMA neurofeedback facilitation during gait- and balance-related motor imagery using fNIRS-NFB. Participants were randomly allocated to intervention (28 patients) or placebo (sham: 26 patients). In the intervention group, the fNIRS signal contained participants' cortical activation information. The primary outcome was TUG improvement 4 weeks postintervention. Results The intervention group showed greater improvement in the TUG test (12.84 ± 15.07 seconds, 95% confidence interval 7.00–18.68) than the sham group (5.51 ± 7.64 seconds, 95% confidence interval 2.43–8.60; group difference 7.33 seconds, 95% CI 0.83–13.83; p = 0.028), even after adjusting for covariates (group × time interaction; F1.23,61.69 = 4.50, p = 0.030, partial η2 = 0.083). Only the intervention group showed significantly increased imagery-related SMA activation and enhancement of resting-state connectivity between SMA and ventrolateral premotor area. Adverse effects associated with fNIRS-mediated neurofeedback intervention were absent. Conclusion SMA facilitation during motor imagery using fNIRS neurofeedback may augment poststroke gait and balance recovery by modulating the SMA and its related network. Classification of Evidence This study provides Class III evidence that for patients with gait disturbance from subcortical stroke, SMA neurofeedback facilitation improves TUG time (UMIN000010723 at UMIN-CTR; umin.ac.jp/english/).

Background: Objective cough frequency measurements are increasingly applied in clinical research. Technological advances enable automated detection and counting of cough events from sound recordings of many hours’ duration. A possible limitation of sound-based cough frequency measurement is the contamination of recordings by environmental coughs (coughs from persons other than the patient). This study aimed to investigate the accuracy of a sound-based cough monitor for detecting and discriminating patient cough from environmental cough. Methods: As part of a stroke trial (ISRCTN40298220), patients on a hospital ward underwent 15-minute recordings using the Leicester Cough Monitor (LCM), a sound-based cough monitor (‘semi-automated counts’). Participants and other persons in the environment were prompted to cough. An observer present in the room recorded the number of patient and environmental coughs (‘live counts’). LCM counts were also compared against a manual cough count, the most commonly used gold standard to determine accuracy (‘manual sound counts’ from listening to recordings), by a blinded assessor who cross-referenced timed cough events from the respective methods. Data for automated, manual and live cough counts were analyzed using agreement statistics. Results: On sound recordings from five patients, there were 65 patient coughs and 78 environmental coughs (manual counts). Absolute agreement for patient cough count between all three measurement methods (LCM automated, live, and manual sound counts) was high, with intra-class correlation coefficient of 0.94 [95% confidence intervals (CI): 0.74, 0.99]. The proportion of exact agreements for patient cough between LCM and manual count was 0.92, and kappa was 0.84 (95% CI: 0.75, 0.93). The LCM showed sensitivity of 0.94 (95% CI: 0.84, 0.98), specificity of 0.91 (95% CI: 0.82, 0.96), positive predictive value of 0.90 (95% CI: 0.79, 0.95) and negative predictive value of 0.95 (95% CI: 0.86, 0.98) for detecting patient coughs. Conclusions: This preliminary study supports the validity of the cough monitor for detecting and discriminating patient from environmental cough. Further validation is recommended, to describe the level of accuracy with greater precision.

Objective: To investigate whether nasogastric tubes (NGTs) increase poststroke pneumonia (PSP), mortality, or poor outcomes in nil-by-mouth acute stroke patients. Methods: This study analyzed prespecified outcomes of PSP at 14 days and mortality and function measured by the modified Rankin Scale at 90 days in 1,217 nil-by-mouth stroke patients at ≤48 hours of symptom onset in a multicenter randomized controlled trial of preventive antibiotics between April 21, 2008, and May 17, 2014. Generalized mixed models adjusted for age, comorbidities, stroke type and severity, and quality of care were used. No patients were lost to follow-up at 14 days, and 36 (3%) were lost at 90 days. Results: Patients with NGT (298 of 1,217 [24.4%]) had more severe strokes (median NIH Stroke Scale score 17 vs 14, p = 0.0001) and impaired consciousness (39% vs 28%, p = 0.001). NGT did not increase PSP (43 of 298 [14.4%] vs 80 of 790 [10.1%], adjusted odds ratio [OR] 1.26 [95% confidence interval (CI) 0.78–2.03], p = 0.35) or 14- and 90-day mortality (33 of 298 [11.1%] vs 78 of 790 [9.9%], adjusted OR 1.10 [95% CI 0.67–1.78], p = 0.71; and 79 of 298 [26.5%] vs 152 of 790 [19.2%], adjusted OR 0.95 [95% CI 0.67–1.33], p = 0.75, respectively). Ninety-day modified Rankin Scale score distribution was comparable between groups (adjusted OR 1.14 [95% CI 0.87–1.56], p = 0.08). PSP independently increased 90-day mortality (40 of 123 [32.5%] vs 191 of 965 [19.8%], adjusted OR 1.71 [95% CI 1.11–2.65], p = 0.015) and was not prevented by antibiotics in patients with NGT (adjusted OR 1.1 [95% CI 0.89–1.54], p = 0.16). Conclusions: Early NGT does not increase PSP incidence, mortality, or poor functional outcomes and can be used safely in acute stroke patients.

Comment inThe yin and yang of magnesium and calcium: New genetic insights for stroke? [Neurology. 2019]; International audience; Objective To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach. Methods Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases). Results In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10 −4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10 −4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype. Conclusions This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.

Background and aim Pyrexia-dependent clinical algorithms may under or overdiagnose stroke-associated pneumonia. This study investigates whether inclusion of elevated C-reactive protein as a criterion improves diagnosis. Methods The contribution of C-reactive protein ≥30 mg/l as an additional criterion to a Centers for Disease Control and Prevention-based algorithm incorporating pyrexia with chest signs and leukocytosis and/or chest infiltrates to diagnose stroke-associated pneumonia was assessed in 1088 acute stroke patients from 37 UK stroke units. The sensitivity, specificity, and positive predictive value of different approaches were assessed using adjudicated stroke-associated pneumonia as the reference standard. Results Adding elevated C-reactive protein to all algorithm criteria did not increase diagnostic accuracy compared with the algorithm alone against adjudicated stroke-associated pneumonia (sensitivity 0.74 (95% CI 0.65–0.81) versus 0.72 (95% CI 0.64–0.80), specificity 0.97 (95% CI 0.96–0.98) for both; kappa 0.70 (95% CI 0.63–0.77) for both). In afebrile patients (n = 965), elevated C-reactive protein with chest and laboratory findings had sensitivity of 0.84 (95% CI 0.67–0.93), specificity of 0.99 (95% CI 0.98–1.00), and kappa 0.80 (95% CI 0.70–0.90). The modified algorithm of pyrexia or elevated C-reactive protein and chest signs with infiltrates or leukocytosis had sensitivity of 0.94 (95% CI 0.87–0.97), specificity of 0.96 (95% CI 0.94–0.97), and kappa of 0.88 (95% CI 0.84–0.93) against adjudicated stroke-associated pneumonia. Conclusions An algorithm consisting of pyrexia or C-reactive protein ≥30 mg/l, positive chest signs, leukocytosis, and/or chest infiltrates has high accuracy and can be used to standardize stroke-associated pneumonia diagnosis in clinical or research settings. Trial Registration http://www.isrctn.com/ISRCTN37118456

Background and Purpose— Cough protects the lungs from aspiration. We investigated whether respiratory muscle training may improve respiratory muscle and cough function, and potentially reduce pneumonia risk in acute stroke. Methods— We conducted a single-blind randomized placebo-controlled trial in 82 patients with stroke (mean age, 64±14 years; 49 men) within 2 weeks of stroke onset. Participants were masked to treatment allocation and randomized to 4 weeks of daily expiratory (n=27), inspiratory (n=26), or sham training (n=25), using threshold resistance devices. Primary outcome was the change in peak expiratory cough flow of maximal voluntary cough. Intention-to-treat analyses were conducted using ANCOVA, adjusting for baseline prognostic covariates. Results— There were significant improvements in the mean maximal inspiratory (14 cmH 2 O; P 2 O; P P =0.0002) between baseline and 28 days in all groups. Peak expiratory cough flow of capsaicin-induced reflex cough was unchanged. There were no between-group differences that could be attributed to respiratory muscle training. There were also no differences in the 90-day incidence of pneumonia between the groups ( P =0.65). Conclusions— Respiratory muscle function and cough flow improve with time after acute stroke. Additional inspiratory or expiratory respiratory muscle training does not augment or expedite this improvement. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN40298220.

Background and Purpose— Diagnosis of pneumonia complicating stroke is challenging, and there are currently no consensus diagnostic criteria. As a first step in developing such consensus-based diagnostic criteria, we undertook a systematic review to identify the existing diagnostic approaches to pneumonia in recent clinical stroke research to establish the variation in diagnosis and terminology. Methods— Studies of ischemic stroke, intracerebral hemorrhage, or both, which reported occurrence of pneumonia from January 2009 to March 2014, were considered and independently screened for inclusion by 2 reviewers after multiple searches using electronic databases. The primary analysis was to identify existing diagnostic approaches for pneumonia. Secondary analyses explored potential reasons for any heterogeneity where standard criteria for pneumonia had been applied. Results— Sixty-four studies (56% ischemic stroke, 6% intracerebral hemorrhage, 38% both) of 639 953 patients were included. Six studies (9%) reported no information on the diagnostic approach, whereas 12 (19%) used unspecified clinician-reported diagnosis or initiation of antibiotics. The majority used objective diagnostic criteria: 20 studies (31%) used respiratory or other published standard criteria; 26 studies (41%) used previously unpublished ad hoc criteria. The overall occurrence of pneumonia was 14.3% (95% confidence interval 13.2%–15.4%; I 2 =98.9%). Occurrence was highest in studies applying standard criteria (19.1%; 95% confidence interval 15.1%–23.4%; I 2 =98.5%). The substantial heterogeneity observed was not explained by stratifying for other potential confounders. Conclusions— We found considerable variation in terminology and the diagnostic approach to pneumonia. Our review supports the need for consensus development of operational diagnostic criteria for pneumonia complicating stroke.

Introduction Each year 7 million people die of stroke worldwide; most deaths are caused by chest infections. Patients with acute stroke have impaired voluntary cough flow, associated with increased risk of chest infections. Reduced functional residual capacity (FRC) could lead to impaired cough flow. We therefore compared FRC in acute hemiparetic stroke patients and controls and explored its relationship with volume inspired before cough and voluntary cough peak flow. Methods 21 patients within 2 weeks of first-ever middle cerebral artery territory (MCA) infarct (mean (SD) age 68 (11) years, 10 females) and 30 controls (58 (11) years, 15 females) underwent FRC and voluntary cough testing (cough inspired volume and peak flow) while semirecumbent. FRC was expressed as % predicted; cough inspired volume was expressed as % predicted VC and cough peak flow as % predicted PEF. A clinician scored stroke severity using the National Institutes of Health Stroke Scale (NIHSS). Results Patients’ reclined FRC, voluntary cough peak flowand cough inspired volume were reduced compared with controls (p

Objective: To describe the content and delivery of the adapted London Stroke Carers Training Course intervention evaluated in the Training Caregivers after Stroke (TRACS) trial. Setting: The London Stroke Carers Training Course is a structured training programme for caregivers of inpatients who are likely to return home after their stroke. The course was delivered by members of the multidisciplinary team while the patient was in the stroke unit with one recommended ‘follow through’ session after discharge home. Intervention: The intervention consists of 14 training components (six mandatory) that were identified as important knowledge/skills that caregivers would need to be able to care for the stroke patient after discharge home. Following national training days, the London Stroke Carers Training Course was disseminated to intervention sites by the cascade method of implementation. Results: The intervention was adapted for implementation across a range of stroke units. Training days were well attended (median 2.5 and 2.0 attendees per centre for the first and second days, respectively) and the feedback positive, demonstrating ‘face validity’ for the intervention. However cascading of this training to other members of the multidisciplinary team was not consistent, with 7/18 centres recording no cascade training. Conclusion: The adapted London Stroke Carers Training Course provided a training programme that could be delivered in a standardised, structured way in a variety of stroke unit settings throughout the UK. The intervention was well received by stroke unit staff, however, the cascade method of implementation was not as effective as we would have wished.

Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. For patients and clinicians the possibility of relying on valid predictors of recovery is an important asset in the clinical management of stroke-related impairment. Age, level of education, type and severity of initial symptoms are established predictors of recovery. However, anatomical predictors are still poorly understood. In this prospective longitudinal study, we intended to assess anatomical predictors of recovery derived from diffusion tractography of the perisylvian language networks. Our study focused on the arcuate fasciculus, a language pathway composed of three segments connecting Wernicke’s to Broca’s region (i.e. long segment), Wernicke’s to Geschwind’s region (i.e. posterior segment) and Broca’s to Geschwind’s region (i.e. anterior segment). In our study we were particularly interested in understanding how lateralization of the arcuate fasciculus impacts on severity of symptoms and their recovery. Sixteen patients (10 males; mean age 60 ± 17 years, range 28–87 years) underwent post stroke language assessment with the Revised Western Aphasia Battery and neuroimaging scanning within a fortnight from symptoms onset. Language assessment was repeated at 6 months. Backward elimination analysis identified a subset of predictor variables (age, sex, lesion size) to be introduced to further regression analyses. A hierarchical regression was conducted with the longitudinal aphasia severity as the dependent variable. The first model included the subset of variables as previously defined. The second model additionally introduced the left and right arcuate fasciculus (separate analysis for each segment). Lesion size was identified as the only independent predictor of longitudinal aphasia severity in the left hemisphere [beta = −0.630, t(−3.129), P = 0.011]. For the right hemisphere, age [beta = −0.678, t(–3.087), P = 0.010] and volume of the long segment of the arcuate fasciculus [beta = 0.730, t(2.732), P = 0.020] were predictors of longitudinal aphasia severity. Adding the volume of the right long segment to the first-level model increased the overall predictive power of the model from 28% to 57% [F(1,11) = 7.46, P = 0.02]. These findings suggest that different predictors of recovery are at play in the left and right hemisphere. The right hemisphere language network seems to be important in aphasia recovery after left hemispheric stroke.

Summary Background Most patients who have had a stroke are dependent on informal caregivers for activities of daily living. The TRACS trial investigated a training programme for caregivers (the London Stroke Carers Training Course, LSCTC) on physical and psychological outcomes, including cost-effectiveness, for patients and caregivers after a disabling stroke. Methods We undertook a pragmatic, multicentre, cluster randomised controlled trial with a parallel cost-effectiveness analysis. Stroke units were eligible if four of five criteria used to define a stroke unit were met, a substantial number of patients on the unit had a diagnosis of stroke, staff were able to deliver the LSCTC, and most patients were discharged to a permanent place of residence. Stroke units were randomly assigned to either LSCTC or usual care (control group), stratified by geographical region and quality of care, and using blocks of size 2. Patients with a diagnosis of stroke, likely to return home with residual disability and with a caregiver providing support were eligible. The primary outcome for patients was self-reported extended activities of daily living at 6 months, measured with the Nottingham Extended Activities of Daily Living (NEADL) scale. The primary outcome for caregivers was self-reported burden at 6 months, measured with the caregivers burden scale (CBS). We combined patient and caregiver costs with primary outcomes and quality-adjusted life-years (QALYs) to assess cost-effectiveness. This trial is registered with controlled-trials.com, number ISRCTN 49208824. Findings We assessed 49 stroke units for eligibility, of which 36 were randomly assigned to either the intervention group or the control group. Between Feb 27, 2008, and Feb 9, 2010, 928 patient and caregiver dyads were registered, of which 450 were in the intervention group, and 478 in the control group. Patients' self-reported extended activities of daily living did not differ between groups at 6 months (adjusted mean NEADL score 27·4 in the intervention group versus 27·6 in the control group, difference –0·2 points [95% CI –3·0 to 2·5], p value=0·866, ICC=0·027). The caregiver burden scale did not differ between groups either (adjusted mean CBS 45·5 in the intervention group versus 45·0 in the control group, difference 0·5 points [95% CI –1·7 to 2·7], p value=0·660, ICC=0·013). Patient and caregiver costs were similar in both groups (length of the initial stroke admission and associated costs were £13 127 for the intervention group and £12 471 for the control group; adjusted mean difference £1243 [95% CI –1533 to 4019]; p value=0·380). Probabilities of cost-effectiveness based on QALYs were low. Interpretation In a large scale, robust evaluation, results from this study have shown no differences between the LSCTC and usual care on any of the assessed outcomes. The immediate period after stroke might not be the ideal time to deliver structured caregiver training. Funding Medical Research Council.

Multimodal CT or MR imaging may be helpful in guiding reperfusion therapy for stroke. However, access to multimodal imaging may frequently be limited. We hypothesised that certain clinical and non-enhanced CT (NECT) findings at initial assessment can potentially predict mismatch on CT perfusion (CTP) in patients with acute ischaemic stroke.We undertook an analysis of prospectively collected clinical and imaging data of consecutive patients with anterior circulation ischaemic stroke who underwent CTP during their initial assessment. NECT was read for early ischaemic change as measured by the Alberta Stroke Program Early CT Score (ASPECTS), and for hyperdense middle cerebral artery sign (HMCAS). CTP images were evaluated for mismatch. Independent clinical and imaging predictors of a CTP mismatch were identified using stepwise logistic regression.Of the 202 patients, 92 (46%) demonstrated a mismatch, 23 (11%) a matched deficit, and 87 (43%) no perfusion deficit. HMCAS on NECT (OR 13.65, 95% CI 6.04-30.81, p0.001), female gender (OR 2.37, 95% CI 1.19-4.72, p = 0.015), atrial fibrillation (OR 2.05, 95% CI 1.02-4.11, p = 0.044), and absence of a history of hypertension (OR 0.46, 95% CI 0.22-0.96, p = 0.037) were independent predictors of a CTP mismatch. HMCAS had 58% sensitivity, 91% specificity, 84% positive predictive value and 72% negative predictive value.A HMCAS on the initial NECT is associated with a high probability of mismatch in acute ischaemic stroke, and may identify patients most likely to benefit from recanalisation treatments when access to multimodal CT or MR facilities is limited.

Background and Purpose— Wake-up ischemic stroke (WUIS) patients are not thrombolysed even if they meet other criteria for treatment. We hypothesized that patients with WUIS showing no or early ischemic changes on brain imaging will have thrombolysis outcomes comparable with those with known time of symptom onset. Methods— Consecutive sampling of a prospective registry of patients with stroke between January 2009 and December 2010 identified 394 thrombolysed patients meeting predefined inclusion criteria, 326 presenting within 0 to 4.5 hours of symptom onset (Reference Group) and 68 WUIS patients. Inclusion criteria were last seen normal 4.5 hours (WUIS) or presented Results— The groups were comparable for mean age (72.8 versus 73.9 years; P =0.58) and baseline median National Institutes of Health Stroke Scale score (median 13 versus 12; P =0.34). The proportions of patients with modified Rankin Scale 0 to 2 (38% versus 37%; P =0.89) and modified Rankin Scale 0 to 1 (24% versus 16%; P =0.18) at 90 days, any ICH (20% versus 22%; P =0.42) and symptomatic intracerebral hemorrhage (3.4% versus 2.9%; P =1.0) were comparable after adjusting for age, stroke severity, and imaging changes. Only 9/394 (2%) patients were lost to follow-up. Conclusions— Thrombolysis in selected patients with WUIS is feasible, and its outcomes are comparable with those thrombolysed with 0 to 4.5 hours.

Background and Purpose— Wake-up ischemic stroke (WUIS) patients are not eligible for thrombolysis; the a priori hypothesis was that thrombolysis of selected WUIS patients who meet clinical and imaging criteria for treatment is associated with better outcomes. Methods— The sample consisted of consecutive WUIS patients who fulfilled predefined criteria: (1) were last seen normal >4.5 hours and Results— WUIS patients constituted 10.5% (193/1836) of all stroke admissions. Inclusion criteria were fulfilled by 122 (63%) patients, of whom 68 (56%) were thrombolysed. Thrombolysed and nonthrombolysed patients were comparable for baseline characteristics, but the median baseline National Institute of Health Stroke Scale score was higher in thrombolysed patients (9 versus 11.5; P =0.034). There was no difference in modified Rankin Scale 0 to 2 (25 [37%] versus 14 [26%]; P =0.346), death (10 [15%] versus 14 [26%]; P =0.122), and symptomatic intracerebral hemorrhage (2 versus 0; P =0.204) between thrombolysed and nonthrombolysed patients. After adjusting for age, sex, and baseline National Institute of Health Stroke Scale score thrombolysis was associated with odds ratio of 5.2 (95% confidence interval 1.3–20.3), P =0.017 for modified Rankin Scale 0 to 2 at 90 days and odds ratio of 0.09 (95% confidence interval 0.02–0.44), P =0.003 for death. Conclusions— Thrombolysis in selected WUIS patients is feasible and may have potential of benefit.

Background: Avoidance of admission through provision of hospital care at home is a scheme whereby health care professionals provide active treatment in the patient9s home for a condition that would otherwise require inpatient treatment in an acute care hospital. We sought to compare the effectiveness of this method of caring for patients with that type of in-hospital care. Methods: We searched the MEDLINE, EMBASE, CINAHL and EconLit databases and the Cochrane Effective Practice and Organisation of Care Group register from the earliest date in each database until January 2008. We included randomized controlled trials that evaluated a service providing an alternative to admission to an acute care hospital. We excluded trials in which the program did not offer a substitute for inpatient care. We performed meta-analyses for trials for which the study populations had similar characteristics and for which common outcomes had been measured. Results: We included 10 randomized trials (with a total of 1327 patients) in our systematic review. Seven of these trials (with a total of 969 patients) were deemed eligible for meta-analysis of individual patient data, but we were able to obtain data for only 5 of these trials (with a total of 844 patients [87%]). There was no significant difference in mortality at 3 months for patients who received hospital care at home (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.54–1.09, p = 0.15). However, at 6 months, mortality was significantly lower for these patients (adjusted HR 0.62, 95% CI 0.45–0.87, p = 0.005). Admissions to hospital were greater, but not significantly so, for patients receiving hospital care at home (adjusted HR 1.49, 95% CI 0.96–2.33, p = 0.08). Patients receiving hospital care at home reported greater satisfaction than those receiving inpatient care. These programs were less expensive than admission to an acute care hospital ward when the analysis was restricted to treatment actually received and when the costs of informal care were excluded. Interpretation: For selected patients, avoiding admission through provision of hospital care at home yielded similar outcomes to inpatient care, at a similar or lower cost.

Purpose Several risk stratification scores for predicting stroke-associated pneumonia have been derived. We aimed to evaluate the performance and clinical usefulness of such scores for predicting stroke-associated pneumonia. Method A systematic literature review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, with application of the Quality Assessment of Diagnostic Accuracy-2 tool. Published studies of hospitalised adults with ischaemic stroke, intracerebral haemorrhage, or both, which derived and validated an integer-based clinical risk score, or externally validated an existing score to predict occurrence of stroke-associated pneumonia, were considered and independently screened for inclusion by two reviewers. Findings We identified nine scores, from eight derivation cohorts. Age was a component of all scores, and the NIHSS score in all except one. Six scores were internally validated and five scores were externally validated. The A2DS2 score (Age, Atrial fibrillation, Dysphagia, Severity [NIHSS], Sex) was the most externally validated in 8 independent cohorts. Performance measures were reported for eight scores. Discrimination tended to be more variable in the external validation cohorts (C statistic 0.67–0.83) than the derivation cohorts (C statistic 0.74–0.85). Discussion Overall, discrimination and calibration were similar between the different scores. No study evaluated influence on clinical decision making or prognosis. Conclusion The clinical prediction scores varied in their simplicity of use and were comparable in performance. Utility of such scores for preventive intervention trials and in clinical practice remains uncertain and requires further study.

We undertook two systematic reviews to determine the levels of respiratory muscle weakness and effects of respiratory muscle training in stroke patients. Two systematic reviews were conducted in June 2011 using a number of electronic databases. Review 1 compared respiratory muscle strength in stroke and healthy controls. Review 2 was expanded to include randomized controlled trials assessing the effects of respiratory muscle training on stroke and other neurological conditions. The primary outcomes of interest were maximum inspiratory and expiratory mouth pressure (maximum inspiratory pressure and maximum expiratory pressure, respectively). Meta-analysis of four studies revealed that the maximum inspiratory pressure and maximum expiratory pressure were significantly lower ( P < 0·00001) in stroke patients compared with healthy individuals (weighted mean difference −41·39 and −54·62 cmH2O, respectively). Nine randomized controlled trials indicate a significantly ( P = 0·0009) greater effect of respiratory muscle training on maximum inspiratory pressure in neurological patients compared with control subjects (weighted mean difference 6·94 cmH2O) while no effect on maximum expiratory pressure. Respiratory muscle strength appears to be impaired after stroke, possibly contributing to increased incidence of chest infection. Respiratory muscle training can improve inspiratory but not expiratory muscle strength in neurological conditions, although the paucity of studies in the area and considerable variability between them is a limiting factor. Respiratory muscle training may improve respiratory muscle function in neurological conditions, but its clinical benefit remains unknown.

Thrombolysis and endovascular interventions have revolutionized stroke treatment, but many patients are excluded from such therapies, and residual disability is common.1 Emerging approaches to enhance poststroke brain repair may have no time constraints and are applicable to most stroke patients. Novel interventions to enhance brain repair include electromagnetic or robotic techniques, brain–computer interface, and restorative cell-based and pharmacological therapies.2–4 A major impediment to translation to patient care, however, is the lack of robust in vivo techniques to monitor the effects of such interventions in humans.3 Noninvasive imaging of the human brain for multiparametric in vivo monitoring of poststroke recovery presents challenges. The clinical application of certain techniques such as positron emission tomography is frequently restricted by radiation exposure, limited resolution, high cost, or difficult access.5–7 Magnetic resonance imaging (MRI), however, is accessible, noninvasive, safe, and versatile, with high resolution, making this an ideal modality for multiparametric in vivo monitoring of stroke recovery. This review concentrates on MRI markers of stroke recovery in experimental models and, when available, in humans (Table). View this table: Table. Magnetic Resonance Options for Imaging Poststroke Recovery ### Angiogenesis The peri-infarct cortex is a unique neurovascular niche, within which angiogenesis is closely and causally linked to neurogenesis through vascular growth factors and chemokines.2 Together with parenchymal astrocytes, angiogenic vessels facilitate synaptogenesis and axonal sprouting.2 Angiogenesis stimulated by cell-based or pharmacological interventions correlates with improved behavioral outcome.2 In rodents, capillary sprouting at the ischemic boundary leads to new vessel development between 2 and 28 days.8 Angiogenesis has been observed in the ischemic penumbra of humans 3 to 4 days after stroke, and higher cerebral blood vessel density has been associated with improved survival.9 Angiogenic vessels are permeable during the early stages of development and become less leaky as they …

Previous research has shown that prism adaptation (prism adaptation) can ameliorate several symptoms of spatial neglect after right-hemisphere damage. But the mechanisms behind this remain unclear. Recently we reported that prisms may increase leftward awareness for neglect in a task using chimeric visual objects, despite apparently not affecting awareness in a task using chimeric emotional faces ( Sarri et al., 2006 ). Here we explored potential reasons for this apparent discrepancy in outcome, by testing further whether the lack of a prism effect on the chimeric face task task could be explained by: i) the specific category of stimuli used (faces as opposed to objects); ii) the affective nature of the stimuli; and/or iii) the particular task implemented, with the chimeric face task requiring forced-choice judgements of lateral ‘preference’ between pairs of identical, but left/right mirror-reversed chimeric face tasks (as opposed to identification for the chimeric object task). We replicated our previous pattern of no impact of prisms on the emotional chimeric face task here in a new series of patients, while also similarly finding no beneficial impact on another lateral ‘preference’ measure that used non-face non-emotional stimuli, namely greyscale gradients. By contrast, we found the usual beneficial impact of prism adaptation (prism adaptation) on some conventional measures of neglect, and improvements for at least some patients in a different face task, requiring explicit discrimination of the chimeric or non-chimeric nature of face stimuli. The new findings indicate that prism therapy does not alter spatial biases in neglect as revealed by ‘lateral preference tasks’ that have no right or wrong answer (requiring forced-choice judgements on left/right mirror-reversed stimuli), regardless of whether these employ face or non-face stimuli. But our data also show that prism therapy can beneficially modulate some aspects of visual awareness in spatial neglect not only for objects, but also for face stimuli, in some cases.

This review article describes thrombolysis as an effective treatment for acute ischemic stroke. The aim of acute thrombolytic therapy is to break up the thrombus or embolus occluding a cerebral artery and restore perfusion to reversibly ischemic brain. Current evidence from randomized, controlled trials limits the therapeutic time window for thrombolysis to 4.5 h for intravenous treatment and 6 h for intra-arterial treatment. Guidelines emphasize the need to identify acute stroke as a clinical priority, and to develop ‘fast-track’ protocols for the early assessment and treatment of stroke patients. The use of advanced imaging techniques and adjuncts to thrombolysis that may have the potential to improve the ability to select patients who may benefit from reperfusion therapy, and allow treatment decisions to be based on individual brain pathophysiology rather than arbitrary time windows, are discussed.

Although hypertension is known to cause brain damage and cognitive impairment, epidemiological studies suggest that lower blood pressure (BP) in patients with established cerebrovascular disease is associated with more rapid cognitive decline. We investigated the relationship between 24-h ambulatory blood pressure (ABP) measurements, cerebrovascular disease load and cognitive performance in patients with hypertensive cerebrovascular disease.Eighty-eight patients (mean age 65+9 years) with hypertensive cerebrovascular disease on MRI were recruited. BP was controlled optimally. ABP monitoring, quantitative MRI analysis of white matter lesion (WML) volume and executive cognitive function tests were performed. The relationships between ABP variables, WML volume and executive test performance were examined using regression analyses to adjust for age, sex, vascular risk profile and premorbid intelligence.Patients had a mean daytime ABP of 96+10 mmHg and mean night-time ABP of 88+11 mmHg (P = 0.001). Median WML volume was 8464 mm3. There were no significant associations between ABP variables and supratentorial WML volumes. Infratentorial WML volume correlated negatively with night-time mean BP (r = -0.6, P = 0.002) and positively with nocturnal dipping (r = 0.6, P = 0.002). Higher night-time mean BP was an independent predictor of reduced infratentorial WML volume (R2: 0.460, P = 0.008).Infratentorial WML volume correlated with impairments of phonemic verbal fluency (r = 0.5, P0.001) and choice reaction time (r = 0.7, P0.005).Physiological falls in nocturnal BP may be associated with increased infratentorial WML volume and cognitive dysfunction in optimally controlled hypertensive patients with cerebrovascular disease.

A Consensus Conference on Stroke in 1988 concluded that rehabilitation for stroke in the United Kingdom was poorly organised, was not based on evidence, and was associated with poor outcomes compared with similar health care systems. In addition, there were significant variations in the quality of services and outcome across different areas of the country. Efforts to improve care included increased investment into services and research, development of multidisciplinary national guidelines for all aspects of stroke care, and a regular national audit of stroke rehabilitation. The last 20 years have seen dramatic improvements in the development of a coherent policy for the management of stroke patients in the United Kingdom, underpinned by well-organised services within a framework of guidelines and performance review. However, further work is needed to increase the evidence base for the nature, duration, and effectiveness of complex rehabilitation interventions and to improve multidisciplinary interactions and communications with patients and their caregivers. Of the further work required, the leading priority is to increase therapy input to make the best use of time that patients spend in rehabilitation settings.

Background: Small-vessel cerebrovascular disease and vascular cognitive impairment are more prevalent in hypertensive subjects of black African origin compared with Caucasians, but the relationships between blood pressure (BP), regional white matter damage and neuropsychological function have not been studied in well-characterised samples of subjects belonging to different ethnicities. Methods: Twenty-four-hour ambulatory BP, brain white matter lesion volumes on magnetic resonance imaging and executive cognitive function were compared in 41 Caucasian and 47 African-Caribbean subjects on optimal treatment attending a hypertension clinic. Results: African-Caribbean subjects were 4 years younger but had been hypertensive for 3 years longer than Caucasians. Their mean 24-hour systolic (136.6 vs. 129.4 mm Hg, p = 0.011) and diastolic (77.8 vs. 72.6 mm Hg, p = 0.006) BP were also higher despite being well-controlled. In multivariate models, African-Caribbean subjects had a greater parieto-occipital white matter lesion volume [adjusted difference: 319 mm3 (95% CI: 62–575), p = 0.016] and poorer performance on executive function [time difference: 0.375 s (95% CI: 0.191–0.558), p = 0.0001] and verbal fluency [score difference: –6.863 (95% CI: –12.531 to –1.195), p = 0.018] tests after adjusting for covariance in age, gender, vascular risk profile, duration of hypertension and education, and premorbid intelligence. Conclusions: African-Caribbean ethnicity was independently related to increased hypertensive white matter damage and executive cognitive dysfunction, the reasons for which merit further investigation.

Prism adaptation to rightward optical shifts during visually guided pointing is considered a promising intervention in right-hemisphere stroke patients with left spatial neglect. Conventionally, prism adaptation is assessed via aftereffects, on subjective straight ahead (SSA) pointing with eyes closed; or by visual open-loop pointing (VOL), i.e. pointing to a visual target without seeing the hand. Previous data suggest indirectly that prism aftereffects in neglect patients may be larger (pathologically so) when assessed by SSA than by VOL. But these measures have never been directly compared within the same patients after identical prism exposure. Accordingly we implemented both measures here within the same group of 13 neglect patients and 13 controls. Prism aftereffects were much larger for SSA than VOL in neglect patients, falling outside the normative range only for SSA. This may arise because the SSA task can itself involve aspects of neglect that may be ameliorated by the prism intervention, hence showing abnormal changes after prisms. The extent of SSA change after prisms varied between patients, and correlated with improvements on a standard cancellation measure for neglect. The lesions of patients who did versus did not show neglect improvement immediately after prisms provide an initial indication that lack of improvement may potentially relate to cortical damage in right intraparietal sulcus and white matter damage in inferior parietal lobe and middle frontal gyrus. Future studies of possible rehabilitative impact from prisms upon neglect may need to consider carefully how to measure prism adaptation per se, separately from any impact of such adaptation upon manifestations of neglect.

Objective Diagnosing stroke-associated pneumonia (SAP) is challenging and may result in inappropriate antibiotic use or confound research outcomes. This study evaluates the diagnostic accuracy of algorithm-defined versus physician-diagnosed SAP in 1088 patients who had dysphagic acute stroke from 37 UK stroke units between 21 April 2008 and 17 May 2014. Methods SAP in the first 14 days was diagnosed by a criteria-based algorithm applied to blinded patient data and independently by treating physicians. Patients in whom diagnoses differed were reassigned following blinded adjudication of individual patient records. The sensitivity, specificity, positive predictive value (PPV) and diagnostic OR of algorithmic and physician diagnosis of SAP were assessed using adjudicated SAP as the reference standard. Agreement was assessed using the κ statistic. Results Physicians diagnosed SAP in 176/1088 (16%) and the algorithm in 123/1088 (11.3%) patients. Diagnosis agreed in 885/1088 (81.3%) patients (κ 0.22 (95% CI 0.14 to 0.29)). On a blinded review, 129/1088 (11.8%) patients were adjudicated as patients with SAP. The algorithm and the physicians had high specificity (97% (95% CI 96% to 98%) and 90% (95% CI 88% to 92%), respectively) but only moderate sensitivity (72% (95% CI 64% to 80%) and 65% (95% CI 56% to 73%), respectively) in diagnosing SAP. The algorithm showed better PPV (76% (95% CI 67% to 83%) vs 48% (95% CI 40% to 55%)), diagnostic OR (80 (95% CI 42 to 136) vs 18 (95% CI 12 to 27)) and agreement (κ 0.70 (95% CI 0.63 to 0.78) vs 0.48 (95% CI 0.41 to 0.54)) than physician diagnosis with adjudicated SAP. Conclusions Algorithm-based approaches can standardise SAP diagnosis for clinical practice and research. Trial registration number ISRCTN37118456; Post-results.

Background Deep vein thrombosis (DVT) is a common complication of acute stroke, but the new incidence in the era of improved specialist input in stroke care is yet unknown. The models for VTE diagnosis is well established, but prediction models to target at-risk patients for pharmacological prophylaxis is lacking and requires further research, particularly in the aftermath of acute stroke. Objectives To predict DVT after acute stroke using markers of haemostatic activation and stroke severity scores. Methods We examined the clinical utility of laboratory factors such as thrombin generation, D-dimer, fibrinogen alongside clinical factors (National Institute of Health Stroke Scale and Barthel Index) in the prediction of asymptomatic DVT, among 92 consecutively admitted patients. Results One in five patients (19.6%) had objectively confirmed DVT (6 proximal, 12 distal). Thrombolytic therapy did not protect against DVT, with 21% (6/29) of patients treated with r-tPA went on to develop DVT. Thrombin generation and fibrinogen had no clinical utility, but D-dimer at baseline and week 2 had high clinical potential in the prediction of asymptomatic DVT (2425 ng/mL versus 1010 ng/mL; p = 0.001) and (2240 Vs 970 ng/mL; p < 0.001) respectively. Patients with DVT had worse stroke severity, and are functionally less able, with lower Barthel index (p = 0.05), and high National Institute of Health Stroke Score (p = 0.07). Conclusion Thrombolytic therapy and specialist stroke intervention does not protect against DVT risk. D-dimer concentration within 48 h of acute stroke is independently associated with development of DVT. This observation would require confirmation in a large study.

Introduction. Stroke remains a global leading cause of death and disability. Traditional description of plasma biology in the aftermath of acute ischaemic stroke favours development of hypercoagulability, resulting from complex interplay between plasma and endothelial factors. However, no single assay measures the overall global coagulation process. We postulate that thrombin generation would assist in identifying coagulation abnormalities after acute stroke.Aim. To investigate the coagulation abnormalities after acute ischaemic stroke using thrombin generation.Methods. We evaluated thrombin generation, measured with calibrated automated thrombography in stroke of different aetiological types (n=170) within 48 hours of symptoms onset (baseline) and in the second week (time 2) and in normal healthy volunteers (n=71).Results. Two-point thrombin generation assays showed prolonged lag time and time to peak at baseline (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7);p=0.005) and (3.3 (2.9, 4.0) versus 3.6 (3.2, 4.7);p=0.002), respectively, and at time 2 (3.5 (2.9, 4.2) versus 4.0 (3.1, 4.9);p=0.004) and (5.9 (5.3, 6.6) versus 6.8 (5.8, 7.7)p=0.05), respectively, in cardioembolic stroke (n=39), when compared to noncardioembolic stroke (n=117). The result was reproduced in multiple comparisons between acute ischaemic stroke subgroups and normal healthy volunteers. Endogenous thrombin potential and peak thrombin did not indicate hypercoagulability after acute ischaemic stroke, and thrombolytic therapy did not affect thrombin generation assays.Conclusion. Our findings suggest that thrombin generation in platelet poor plasma is not useful in defining hypercoagulability in acute ischaemic stroke. This is similar to observed trend in coronary artery disease and contrary to other hypercoagulable states.

Stroke is the largest single cause of severe physical disability and rehabilitation to reduce functional deficits is the most effective treatment. Occupational therapists play a central role in rehabilitation as members of a multidisciplinary team. Occupational therapy is a client-centered profession that uses meaningful activities across the spectrum of physical and mental domains to reduce limitations after stroke. Where remediation is not possible, occupational therapists implement compensatory strategies to promote independence. Rehabilitation is based on the concept of brain plasticity, which implies that it is possible to modulate or facilitate cerebral reorganization by external inputs. Occupational therapy activities are specifically geared to promote this re-education process and encourage the development of lost skills while accommodating for specific physical, cognitive or affective impairments. Principles of motor, sensory, cognitive and affective rehabilitation are incorporated into effective task-specific activities and environments are adapted to create the optimum conditions for successful rehabilitation. Several promising new rehabilitation approaches, based on neuropsychology and technological advances, have been developed to complement therapy inputs and exploit the brain's capacity to recover from stroke.

Vascular cognitive impairment (V.C.I.) encompasses all forms of cognitive loss associated with cerebrovascular disease and ischaemic brain injury. It includes cognitive impairment related to stroke, cortical and subcortical infarcts, silent infarcts and strategic infarcts, white matter lesions associated with small vessel disease, and specific arteriopathies such as CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy). Recent studies have demonstrated that VCI is most commonly of a subcortical aetiology with small vessel disease being the major cause. VCI plays an important part in patients with other forms of dementia, such as Alzheimer's disease, who have coexisting vascular lesions and it has been proposed that VCI may be the most common form of cognitive impairment in older people, with a prevalence of 5% in people over the age of 65. In view of the aging population and the growing magnitude of vascular disease in western society, the prevalence of subcortical VCI is likely to increase, with a greater impact on patients and health care providers. In this article, we will review the cerebrovascular pathology underlying subcortical VCI and its role in mediating the characteristic cognitive deficits.

There is little available evidence to demonstrate how cough strength mediates the risk of aspiration-related pneumonia in acute stroke. Our secondary analysis of trial data indicates that risk of pneumonia reduces with increasing peak cough flow (PCF) of voluntary cough (OR 0.994 for each 1 L/min increase in PCF, 95% CI 0.988 to 1.0, p=0.035); and to a lesser degree with increasing PCF of reflex cough (OR 0.998 for each 1 L/min increase in PCF, 95% CI 0.992 to 1.004, p=0.475). These data serve hypothesis generation. Further studies are needed to confirm these findings and validate their clinical utility. Clinical trial registration number ISRCTN40298220 (post-results).

Background and Purpose— Desaturation during swallowing may help to identify aspiration in stroke patients. This study investigated pulse oximetry, bedside swallowing assessment (BSA), and videofluoroscopy as tests for detecting aspiration after stroke. Methods— Swallowing was assessed in 189 stroke patients (mean±SD age, 70.9±12.3 years) within 5 days of symptom onset with a modified BSA (water replaced by radio-opaque contrast agent, followed by chest radiography to detect aspiration). Simultaneous pulse oximetry recorded the greatest desaturation from baseline for 10 minutes from modified BSA onset. Videofluoroscopy was undertaken in 54 (28%) patients. Results— Modified BSA showed a safe swallow in 98 (51.9%), unsafe swallow in 85 (45.0%), and silent aspiration in 6 (3.2%) patients. During swallowing, desaturation by >2% occurred in 27 (27.6%) and by >5% in 3 (3.1%) of the 98 safe-swallow patients on modified BSA. Of the 85 unsafe-swallow patients, only 28 (32.9%) desaturated by >2% and 6 (7.1%) by >5%. Desaturation did not occur in any of the 6 silent aspirators. With the modified BSA to detect aspiration, sensitivity and specificity, respectively, were 0.31 and 0.72 for desaturation >2% and 0.07 and 0.97 for desaturation >5%. By videofluoroscopy, sensitivity and specificity for detecting aspiration were 0.47 and 0.72 for modified BSA, 0.33 and 0.62 for desaturation >2%, and 0.13 and 0.95 for desaturation >5%. Combining a failed modified BSA with desaturation >2% or >5% did not significantly improve predictive values. Conclusions— Modified BSA and pulse oximetry during swallowing, whether alone or in combination, showed inadequate sensitivity, specificity, and predictive values for detection of aspiration compared with videofluoroscopy in stroke patients.

OBJECTIVES: To study motor activation patterns of voluntary and reflex cough adjusted for cough flow rates. METHODS: Surface electromyography (EMG) and cough flow rate were measured in 10 healthy volunteers. Voluntary cough was assessed for 20 efforts in each quintile of increasing cough flow rate. Reflex cough was assessed for 25 efforts produced by nebulised l-tartaric acid. EMG was recorded over the expiratory (rectus abdominis, obliques, lower intercostals) and accessory (trapezius, pectoralis major, deltoid, latissimus dorsi) muscles. EMG activity, burst duration and onset were compared for each quintile of voluntary cough, and between voluntary and reflex cough matched for cough flow rate. RESULTS: EMG activity and burst duration of expiratory and accessory muscles during voluntary cough increased in proportion to cough flow. Expiratory muscles had longer EMG burst duration (difference 68 ms (95% CI 34 to 102), p

Prism adaptation can ameliorate some symptoms of left spatial neglect after right-hemisphere stroke. The mechanisms behind this remain unclear. Prism therapy may increase exploration towards the contralesional side, yet without improving perceptual awareness, as apparently for the left side of chimeric face stimuli (Ferber et al. 2003). However, other prism studies suggest that perceptual awareness might be improved (e.g., Maravita et al., 2003). We tested the impact of prism therapy on visual awareness for the left side of chimeric objects as well as chimeric faces, in three neglect patients. Prism therapy dramatically improved awareness for the identity of the left side of chimeric non-face objects, but had no effect on judging expressions for chimeric faces. The latter may thus be unique in showing no prism benefit.

Background and Purpose— A large proportion of disabled stroke survivors live at home and are supported by informal caregivers. Identification of determinants of caregiver burden will help to target caregiver interventions. Methods— Data on patient, caregiver, and health and social support characteristics were collected prospectively over 1 year in 232 stroke survivors in a randomized trial of caregiver training. The contribution of these variables to caregiver burden score (CBS) and quality of life (QOL) measures at 3 months and 1 year was analyzed using regression models. Results— Stroke patients had a mean age of 74±11 years, and 120 (52%) were men. The mean age of caregivers was 65.7±12.5 years, 149 (64%) were females, and 116 (50%) had received caregiver training. The mean CBS was 48±13 and 38±11 (score range of bad to good 88 to 22) and QOL score was 75±16 and 75±15 (score range of bad to good 0 to 100) at 3 months and 1 year, respectively. CBS and QOL correlated with each other and with patient (age, dependency, and mood), caregiver (age, gender, mood, and training), and support (social services and family networks) variables. Of these, only patient and caregiver emotional status, caregiver age and gender, and participation in caregiver training were independent predictors of either outcome at 3 months. Patient dependency and family support were additional independent predictors at 1 year. Social services support predicted institutionalization but not caregiver outcomes. Conclusion— Advancing age and anxiety in patients and caregivers, high dependency, and poor family support identify caregivers at risk of adverse outcomes, which may be reduced by caregiver training.