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Fibrocartilaginous embolism is a rarely reported cause of spinal cord infarction. Seemingly innocuous activities may be associated with nucleus pulposus material embolising to the spinal cord vasculature. We describe a 36-year-old woman presenting with bilateral arm paraesthesia and chest pain that evolved into an acute cord syndrome. Initial MR scan of spine showed central spinal cord T2-weighted hyperintensity over several vertebral levels, suggesting transverse myelitis. Repeat MR scan after her symptoms persisted showed an acute cord infarction from a presumed fibrocartilaginous embolus. Clinicians should consider fibrocartilaginous embolism in patients presenting with an acute cord syndrome with supportive radiological findings.

Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years.A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH).Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up.PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events.

Objectives Vitamin B12 is crucial for neurologic function, red blood cell production, and DNA synthesis. Deficiency can lead to a wide spectrum of haematologic and neuropsychiatric disorders including subacute combined degeneration of the cord. This report presents a case of a 47 y.o female who presented with subacute combined degeneration of the spinal cord with a normal active B12 level. Results MRI demonstrated high T2 signal throughout the dorsal columns of the cervical and upper thoracic cord without enhancement consistent with subacute combined degeneration of the cord. Her blood count revealed a mild macrocytic anaemia. Total vitamin B12 was 128 pmol/L, confirmed on repeat testing. Functional vitamin B12 deficiency was confirmed by an elevated homocysteine level of 38.6 umol/L (reference range 4.4 to 13.6 umol/L) and elevated serum methylmalonic acid of 20.75 umol/L (reference range Conclusion Our patient had a clinical presentation consistent with B12 deficiency with an erroneously high active B12 level. Functional assays confirmed B12 deficiency, and a serological diagnosis of pernicious anaemia was made. This case illustrates the importance of not relying on any single test to exclude B12 deficiency.

Background Syphilis is increasing in prevalence in the community.1 2 Neurosyphilis has protean manifestations making recognition, diagnosis and early initiation of treatment challenging. Methods/Results We present a case of early syphilitic meningitis in a 37-year-old female presenting with multiple cranial neuropathies (V, VI, VII, VIII and XII) developing over the course of two weeks. This began with a sensation of disequilibrium and unsteady gait, and progressed to difficulty closing both eyes, right lip numbness, bilateral hearing impairment (right, followed by left), and dysarthria. She did not report headache, meningism, features of primary syphilis infection or risk factors for sexually transmitted infections (STIs). Examination confirmed the presence of right-sided trigeminal, bilateral abducens, facial, vestibulocochlear and hypoglossal nerve palsies. Cerebrospinal fluid (CSF) examination was inflammatory (protein 1.28 g/L, glucose 3.8mmol/L) with predominant lymphocytosis (76%, WCC 441 x 106/L). Magnetic resonance imaging (MRI) demonstrated post-contrast enhancement of the trigeminal nerve at the pons, as well as facial and vestibulocochlear nerves at the geniculate ganglion with no leptomeningeal enhancement. Our patient was diagnosed with neurosyphilis on serum and CSF serological testing (Serum Treponema pallidum particle agglutination assay (TPPA) positive, chemiluminescent microparticle immunoassay (CMIA) IgG and IgM positive, rapid plasma reagen 1:32. CSF TPPA positive, Venereal Disease Research Laboratory test titre of 1:8). She was treated with intravenous benzylpenicillin with rapid improvement in her cranial neuropathies. Conclusions This is the most extensive cranial neuropathy reported with syphilitic infections to date. Neurosyphilis should be considered as a differential in patients presenting with multiple cranial neuropathies. References Kojima N, Klausner J. An update on the global epidemiology of syphilis. Curr Epidemiol Rep 2018;5(1):24–38. Ghanem K, Ram S, Rice P. The modern epidemic of syphilis. N Engl J Med 2020;382(24):2379–80.

Background There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. Methods We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. Results Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. Conclusion Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

Background and Purpose— Women are reported to have poorer health-related quality of life (HRQoL) after stroke than men, but the underlying reasons are uncertain. We investigated factors contributing to the sex differences. Methods— Individual participant data on 4288 first-ever strokes (1996–2013) were obtained from 4 high-quality population-based incidence studies from Australasia and Europe. HRQoL utility scores among survivors after stroke (range from negative scores=worse than death to 1=perfect health) were calculated from 3 scales including European Quality of Life-5 Dimensions, Short-Form 6-Dimension, and Assessment of Quality of Life at 1 year (3 studies; n=1210) and 5 years (3 studies; n=1057). Quantile regression was used to estimate the median differences in HRQoL for women compared to men with adjustment for covariates. Study factors included sociodemographics, prestroke dependency, stroke-related factors (eg, stroke severity), comorbidities, and poststroke depression. Study-specific median differences were combined into pooled estimates using random-effect meta-analysis. Results— Women had lower pooled HRQoL than men (median difference unadjusted 1 year, −0.147; 95% CI, −0.258 to −0.036; 5 years, −0.090; 95% CI, −0.119 to −0.062). After adjustment for age, stroke severity, prestroke dependency, and depression, these pooled median differences were attenuated, more greatly at 1 year (−0.067; 95% CI, −0.111 to −0.022) than at 5 years (−0.085; 95% CI, −0.135 to −0.034). Conclusions— Women consistently exhibited poorer HRQoL after stroke than men. This was partly attributable to women’s advanced age, more severe strokes, prestroke dependency, and poststroke depression, suggesting targets to reduce the differences. There was some evidence of residual differences in HRQoL between sexes but they were small and unlikely to be clinically significant.

© 2019 AMPCo Pty Ltd Objectives: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). Design, setting, participants: Men and women aged 55–60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. Methods: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55–60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. Main outcome: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. Results: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. Conclusions: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

Background: Outcomes after subarachnoid hemorrhage (SAH) have been rarely examined in large cohorts. Methods: This is an extension of the International Stroke Outcomes Study (INSTRUCT) pooling 13 ‘ideal’ stroke incidence studies (n=657 with SAH from 1993-2017, median age 56 years; 46% men). The primary outcomes were mortality and functional outcome (mRS score 3-5). Harmonized study factors included age, sex, behaviors (current smoking, alcohol intake), comorbidities (history of hypertension, ischemic heart disease, atrial fibrillation), stroke severity (e.g. NIHSS score) and year of stroke. In the pooled dataset, we estimated predictors of mortality using Poisson regression, to estimate incidence rate ratio (IRR) at 1 month (11 studies), 1 year (12 studies) and 5 years (7 studies). Generalized equation estimates in the log-binomial family were used to calculate risk ratios (RRs) for predictors of poor functional outcome at 1 month (5 studies) and 1 year (8 studies). Results: Mortality was 33% at 1 month, 43% at 1 year, and 47% at 5 years (Fig 1). Poor functional outcome was 25% at 1 month and 15% at 1 year (Fig 1). In multivariable analysis, age and stroke severity were associated with mortality at all time points, together with current smoking at 1 and 5 years, and history of hypertension at 5 years (Fig 2). Poor functional outcome was predicted by age (RR 1.03; 95% CI 1.01-1.04) at 1 month and by age (RR 1.04; 95% CI 1.00-1.08) and stroke severity (RR 1.94; 95% CI 1.02-2.87) at 1 year. Conclusion: Risk factors that predict SAH incidence including hypertension and smoking make outcomes worse. Better management of older patients and those with severe strokes could improve outcomes after SAH.

Ideal Chern insulating phases arise in two-dimensional systems with broken time-reversal symmetry. They are characterized by having nearly-flat bands, and a uniform quantum geometry -- which combines the Berry curvature and quantum metric -- and by being incompressible. In this work, we analyze the role of the quantum geometry in ideal Chern insulators aiming to describe transport in presence of external out-of-plane magnetic and electric fields. We firstly show that in the absence of external perturbations, novel Berry connections appear in ideal Chern insulating phases. Secondly, we provide a detailed analysis of the deformation of the quantum geometry once weak out-of-plane magnetic fields are switched on. The perturbed Berry curvature and quantum metric provide an effective quantum geometry, which is analyzed in the insulating regime and provides an application of our novel connections. The conditions under which the Girvin-MacDonald-Platzman algebra is realized in this situation are discussed. Furthermore, an investigation of electrical transport due to the new effective quantum geometry is presented once an electric field is added. Restricting to the case of two bands in the metallic regime the quantum metric appears as measurable quantum mechanical correction in the Hall response. Our findings can be applied, for instance, to rhombohedral trilayer graphene at low energies., Comment: 13 pages plus appendices, 5 figures

Objectives: To examine sex differences in disease profiles, management, and survival at 1 and 5 years after ischemic stroke (IS) among people with atrial fibrillation (AF). Methods: We performed a systematic literature search of reports of AF at IS onset according to sex. We undertook an individual participant data meta-analysis (IPDMA) of nine population-based stroke incidence studies conducted in Australasia, Europe, and South America (1993–2014). Poisson regression was used to estimate women:men mortality rate ratios (MRRs). Study-specific MRRs were combined using random effects meta-analysis. Results: In our meta-analysis based on aggregated data from 101 studies, the pooled AF prevalence was 23% (95% confidence interval [CI]: 22%–25%) in women and 17% (15%–18%) in men. Our IPDMA is of 1,862 IS-AF cases, with women (79.2 ± 9.1, years) being older than men (76.5 ± 9.5, years). Crude pooled mortality rate was greater for women than for men (1-year MRR 1.24; 1.01–1.51; 5-year 1.12; 1.03–1.22). However, the sex difference was greatly attenuated after accounting for age, prestroke function, and stroke severity (1-year 1.09; 0.97–1.22; 5-year 0.98; 0.84–1.16). Women were less likely to have anticoagulant prescription at discharge (odds ratio [OR] 0.94; 95% CI: 0.89–0.98) than men when pooling IPDMA and aggregated data. Conclusions: AF was more prevalent after IS among women than among men. Among IS-AF cases, women were less likely to receive anticoagulant agents at discharge; however, greater mortality rate in women was mostly attributable to prestroke factors. Further information needs to be collected in population-based studies to understand the reasons for lower treatment of AF in women.

Syphilis is increasingly prevalent in the community. The protean manifestations of neurosyphilis make the recognition, diagnosis and early initiation of treatment challenging. We report a case of early syphilitic meningitis presenting with multiple cranial neuropathies. Cerebrospinal fluid (CSF) examination was inflammatory with predominant lymphocytosis. The patient was diagnosed with neurosyphilis based on serum as well as CSF testing. Intravenous benzylpenicillin treatment resulted in rapid improvement of neurological symptoms. Neurosyphilis should be considered in immunocompetent patients presenting with multiple cranial neuropathies, or isolated cranial neuropathies without vascular risk factors.

The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging.We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline.After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days.Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

The potential for B-vitamins to reduce plasma homocysteine (Hcy) and reduce the risk of Alzheimer's disease (AD) has been described previously. However, the role of Apolipoprotein E є4 (APOE4) in this relationship has not been adequately addressed. This case-control study explored APOE4 genotype in an Australian sample of 63 healthy individuals (female = 38; age = 76.9 ± 4.7 y) and 63 individuals with AD (female = 35, age = 77.1 ± 5.3 y). Findings revealed 55 of 126 participants expressed the APOE4 genotype with 37 of 126 having both AD and the APOE4 genotype. Analysis revealed an increased likelihood of AD when Hcy levels are11.0 µmol/L (p = 0.012), cysteine levels were255 µmol/L (p = 0.033) and serum folate was22.0 nmol/L (p = 0.003; in males only). In females, dietary intake of total folate336 µg/day (p=0.001), natural folate270 µg/day (p = 0.011), and vitamin B2 1.12 mg/day (p = 0.028) was associated with an increased AD risk. These results support Hcy, Cys, and SF as useful biomarkers for AD, irrespective of APOE4 genotype and as such should be considered as part of screening and managing risk of AD.

Background— Women are reported to have greater mortality after stroke than men, but the reasons are uncertain. We examined sex differences in mortality at 1 and 5 years after stroke and identified factors contributing to these differences. Methods and Results— Individual participant data for incident strokes were obtained from 13 population-based incidence studies conducted in Europe, Australasia, South America, and the Caribbean between 1987 and 2013. Data on sociodemographics, stroke-related factors, prestroke health, and 1- and 5-year survival were obtained. Poisson modeling was used to estimate the mortality rate ratio (MRR) for women compared with men at 1 year (13 studies) and 5 years (8 studies) after stroke. Study-specific adjusted MRRs were pooled to create a summary estimate using random-effects meta-analysis. Overall, 16 957 participants with first-ever stroke followed up at 1 year and 13 216 followed up to 5 years were included. Crude pooled mortality was greater for women than men at 1 year (MRR 1.35; 95% confidence interval, 1.24–1.47) and 5 years (MRR 1.24; 95% confidence interval, 1.12–1.38). However, these pooled sex differences were reversed after adjustment for confounding factors (1 year MRR, 0.81; 95% confidence interval, 0.72–0.92 and 5-year MRR, 0.76; 95% confidence interval, 0.65–0.89). Confounding factors included age, prestroke functional limitations, stroke severity, and history of atrial fibrillation. Conclusions— Greater mortality in women is mostly because of age but also stroke severity, atrial fibrillation, and prestroke functional limitations. Lower survival after stroke among the elderly is inevitable, but there may be opportunities for intervention, including better access to evidence-based care for cardiovascular and general health.

Background Women have worse outcomes after stroke than men, and this may be partly explained by stroke severity. We examined factors contributing to sex differences in severity of acute stroke assessed by the National Institutes of Health Stroke Scale. Methods and Results We pooled individual participant data with National Institutes of Health Stroke Scale assessment (N=6343) from 8 population‐based stroke incidence studies (1996–2014), forming part of INSTRUCT (International Stroke Outcomes Study). Information on sociodemographics, stroke‐related clinical factors, comorbidities, and pre‐stroke function were obtained. Within each study, relative risk regression using log‐binominal modeling was used to estimate the female:male relative risk ( RR ) of more severe stroke (National Institutes of Health Stroke Scale>7) stratified by stroke type (ischemic stroke and intracerebral hemorrhage). Study‐specific unadjusted and adjusted RR s, controlling for confounding variables, were pooled using random‐effects meta‐analysis. National Institutes of Health Stroke Scale data were recorded in 5326 (96%) of 5570 cases with ischemic stroke and 773 (90%) of 855 participants with intracerebral hemorrhage. The pooled unadjusted female:male RR for severe ischemic stroke was 1.35 (95% CI 1.24–1.46). The sex difference in severity was attenuated after adjustment for age, pre‐stroke dependency, and atrial fibrillation but remained statistically significant (pooled RR adjusted 1.20, 95% CI 1.10–1.30). There was no sex difference in severity for intracerebral hemorrhage ( RR crude 1.08, 95% CI 0.97–1.21; RR adjusted 1.08, 95% CI 0.96–1.20). Conclusions Although women presented with more severe ischemic stroke than men, much although not all of the difference was explained by pre‐stroke factors. Sex differences could potentially be ameliorated by strategies to improve pre‐stroke health in the elderly, the majority of whom are women. Further research on the potential biological origin of sex differences in stroke severity may also be warranted.

Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66).Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.None.

Background Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event. Methods/Design The AUSPICE is a multicenter, randomized, placebo-controlled, double-blind, clinical trial to formally test whether vaccination with the pneumococcal polysaccharide vaccine protects against cardiovascular events (fatal and nonfatal acute coronary syndromes and ischemic strokes). Cardiovascular outcomes will be obtained during 4 to 5 years of follow-up, through health record linkage with state and national administrative data sets. Conclusion This is the first registered randomized controlled trial (on US, World Health Organization, Australia and New Zealand trial registries) to be conducted to test whether vaccination with the pneumococcal polysaccharide vaccine will reduce cardiovascular events. If successful, vaccination can be readily extended to at-risk groups to reduce the risk of cardiovascular diseases.

Background Impaired health-related quality of life (HRQoL) post stroke is common, though prevalence estimates vary considerably. Few longitudinal studies explore post-stroke patterns of HRQoL and factors contributing to their change over time. Accurately identifying HRQoL after stroke is essential to understanding the extent of stroke effects. Objectives This study aimed to assess change in levels of, and identify independent predictors of, HRQoL over the first 12-months post-stroke. Methods Design. A prospective cohort study. Setting and participants Community-dwelling stroke survivors in metropolitan Newcastle, New South Wales (NSW), Australia. Consecutively recruited stroke patients (n = 134) participated in face-to-face interviews at baseline, 3, 6, 9 and 12 months. Outcome measure HRQoL (measured using the Assessment Quality-of-life).Independent measures. Physical and psycho-social functioning, including depression and anxiety (measured via Hospital Anxiety and Depression Scale), disability (Modified Rankin Scale), social support (Multi-dimensional Scale Perceived Social Support) and community participation (Adelaide Activities Profile). Analyses A linear mixed model was used to establish the predictors of, change in HRQoL over time. Results On multivariable analysis, HRQOL did not change significantly with time post-stroke. Higher HRQoL scores were independently associated with higher baseline HRQoL (P = 0.03), younger age (P = 0.006), lower disability (P = 0.003), greater community participation (P ≤ 0.001) and no history of depression (P = 0.03). Conclusion These results contribute to an understanding of HRQoL in the first year post-stroke. Community participation and stroke-related disability are potentially modifiable risk factors affecting post-stroke HRQoL. Interventions aimed at addressing participation and disability post-stroke should be developed and tested.

Altres ajuts: The Stroke Genetics Network (SiGN) study was funded by a cooperative agreement grant from the US National Institute of Neurological Disorders and Stroke (NINDS), NIH (U01 NS069208 and R01 NS100178). SAHLSIS was supported by the Swedish Heart and Lung Foundation (HLF-20160316), the Swedish Research Council (K2014-64X-14605-12-5), the Swedish Stroke Association, the Swedish state (under the "Avtal om Läkarutbildning och Medicinsk Forskning, ALF") (ALFGBG-720081). Australian Stroke Genetics Collaboration study was supported by the National Health and Medical Research Council, Australia. Stroke Pharmacogenomics and Genetics group was supported by Invictus plus network, Generation project, and Miguel Servet programme from Instituto de Salud Carlos III, GODs project and Epigenesis project from Marató de TV3 Foundation and Agaur from Generalitat de Catalunya Government. Arne Lindgren was supported by the Swedish Heart and Lung Foundation, Region Skåne, Skåne University Hospital, the Freemasons Lodge of Instruction EOS in Lund, Lund University, the Foundation of Färs & Frosta-one of Spar-banken Skåne's ownership Foundations, and the Swedish Stroke Association. Martin Söderholm was supported by grants from the Swedish Stroke Association, the Foundation of Färs & Frosta-one of Sparbanken Skåne's ownership Foundations, and the Swedish government (under the "Avtal om Läkarutbildning och Medicinsk Forskning, ALF"). Annie Pedersen was supported by grants from the Swedish government (under the "Avtal om Läkarutbildning och Medi-cinsk Forskning, ALF") and the Gothenburg Foundation for Neurological Research. Natalia Rost was in part supported by NIH-NINDS (R01NS086905 and R01NS082285). Daniel Strbian was supported by the Finnish Subsidiary Governmental Fund (VTR). The authors thank NINDS for funding the genotyping of patients included in the SiGN study (U01 NS069208 and R01 NS100178) and Sólveig Grétarsdóttir for genotyping a subsample of the SAHLSIS cohort. ObjectiveTo discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study.MethodsThe study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 × 10.ResultsWe identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-Expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p < 10), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1).ConclusionsIn this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.

ObjectiveTo examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke.MethodsIndividual participant data on long-term functional outcome or participation restriction (i.e., handicap) were obtained from 11 stroke incidence studies (1993–2014). Multivariable log-binomial regression was used to estimate the female:male relative risk (RR) of poor functional outcome (modified Rankin Scale score >2 or Barthel Index score ResultsIn unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RRunadjusted 1.32, 95% confidence interval [CI] 1.18–1.48; 5 years: RRunadjusted 1.31, 95% CI 1.16–1.47). However, this difference was greatly attenuated after adjustment for age, prestroke dependency, and stroke severity (1 year: RRadjusted 1.08, 95% CI 0.97–1.20; 5 years: RRadjusted 1.05, 95% CI 0.94–1.18). Women also had greater participation restriction than men (pooled MDunadjusted −5.55, 95% CI −8.47 to −2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MDadjusted −2.48, 95% CI −4.99 to 0.03).ConclusionsWorse outcomes after stroke among women were explained mostly by age, stroke severity, and prestroke dependency, suggesting these potential targets to improve the outcomes after stroke in women.

Introduction: As women suffer worse functional outcomes of stroke than men, they may also face more challenges with community reintegration but data are scarce. We examined sex differences in participation after stroke and which factors might account for these disparities. Methods: INSTRUCT is an individual participant data pooling study of incident strokes obtained from 13 population-based cohorts worldwide. Two of the cohorts (Melbourne ’96-‘99 and Auckland ’02-‘03) included assessment of participation at 5 years after stroke using the London Handicap Scale (LHS). The LHS is used to assess the individual’s perspective of their involvement in life situations including orientation (person’s awareness of surroundings), physical independence, mobility, occupation, social interaction and economic self-efficiency. The total score ranges from 0 (worst disadvantage) to 100 (no disadvantage). Linear regression was used to compare LHS total scores and sub-domains for women compared to men. Study-specific multivariable models incorporated adjustment for socio-demographics, stroke-related factors, pre-stroke health and post-stroke factors were combined using random-effects meta-analysis. Results: At 5 years after stroke, there were data on participation for 351/592 (59%) of survivors in Melbourne and 266/881 (30%) of survivors in Auckland. Women suffered greater participation restriction than men (total LHS, pooled mean difference, MD -5.55 [95% CI -8.47, -2.63]). The magnitude of the difference attenuated after adjusting for covariates (pooled MD -2.48 [-4.99, 0.03]). Significant confounders in study-specific models included age, stroke severity, pre-stroke dependency and pre-stroke dementia for Melbourne; and age, stroke severity and pre-stroke dependency for Auckland. In sub-dimensions, women had greater restriction than men in mobility, physical independence and occupation. Additionally, women in Melbourne experienced poorer social integration and orientation than men. Conclusion: Greater restriction in participation after stroke among women than men was mostly attributable to their advanced age and greater pre-stroke dependency. Interventions targeting participation could reduce the impact of stroke in women.

Background. No previous qualitative exploration of urinary incontinence (UI) or post-stroke urinary incontinence (PSUI) has been undertaken in an Australian population. Purpose. The purpose of this study is to explore the experiences of community-dwelling stroke survivors who were living with UI/PSUI and understand how context shaped those experiences. Methods. A pragmatic approach using thematic analysis was employed for this study. Findings. Four themes emerged from the data: “I’ve got to go”: onset and daily experience of UI; “No one ever mentioned it”: lack of advice and information from the health system; “You can’t enjoy something if you’ve got to go the toilet”: experience of occupational restrictions; and “It’s just a matter of planning”: management strategies. Implications. UI continued well beyond discharge and was shaped by limited advice, distress, and role loss. Occupational therapists are encouraged to engage in assessment, management, and treatment of UI, including the provision of education that promotes continence, attenuates negative experiences, and enhances community participation.

Few longitudinal studies explore post-stroke patterns of psychological morbidity and factors contributing to their change over time. We aimed to explore predictors of post-stroke depression (PSD) and post-stroke anxiety over a 12-month period.A prospective cohort study. Consecutively recruited stroke patients (n=134) participated in face-to-face interviews at baseline, 3, 6, 9, and 12 months. Primary outcome measures were depression and anxiety (measured via Hospital Anxiety and Depression Scale). Independent variables included disability (Modified Rankin Scale), Quality-of-life (Assessment Quality-of-life), social support (Multi-dimensional Scale Perceived Social Support) and community participation (Adelaide Activities Profile (AAP)). Secondary outcomes were predictors of resolution and development of PSD and anxiety.Anxiety (47%) was more common than depression (22%) at baseline. Anxiety (but not depression) scores improved over time. Anxiety post-stroke was positively associated with baseline PSD (p0.0001), baseline anxiety (p0.0001) and less disability (p=0.042). PSD was associated with baseline anxiety (p0.0001), baseline depression (p=0.0057), low social support (p=0.0161) and low community participation (p0.0001). The only baseline factor predicting the resolution of PSD (if depressed at baseline) was increased social support (p=0.0421). Factors that predicted the onset of depression (if not depressed at baseline) were low community participation (p=0.0015) and higher disability (p=0.0057).While more common than depression immediately post-stroke, anxiety attenuates while the burden of depression persists over 12 months. Clinical programs should assess anxiety and depression, provide treatment pathways for those identified, and address modifiable risk factors, especially social support and social engagement. Implications for Rehabilitation Psychological distress post stroke is persisting. Multi-disciplinary teams that establish goals with patients promoting social and community engagement could assist in managing psychological morbidity. A shift towards promoting longer-term monitoring and management of stroke survivors must be undertaken, and should consider the factors that support and hinder psychological morbidity.

Introduction Genome-wide association studies have identified several novel genetic loci associated with stroke risk, but how genetic factors influence stroke outcome is less studied. The Genetics of Ischaemic Stroke Functional outcome network aims at performing genetic studies of stroke outcome. We here describe the study protocol and methods basis of Genetics of Ischaemic Stroke Functional outcome. Methods The Genetics of Ischaemic Stroke Functional outcome network has assembled patients from 12 ischaemic stroke projects with genome-wide genotypic and outcome data from the International Stroke Genetics Consortium and the National Institute of Neurological Diseases Stroke Genetics Network initiatives. We have assessed the availability of baseline variables, outcome metrics and time-points for collection of outcome data. Results We have collected 8831 ischaemic stroke cases with genotypic and outcome data. Modified Rankin score was the outcome metric most readily available. We detected heterogeneity between cohorts for age and initial stroke severity (according to the NIH Stroke Scale), and will take this into account in analyses. We intend to conduct a first phase genome-wide association outcome study on ischaemic stroke cases with data on initial stroke severity and modified Rankin score within 60–190 days. To date, we have assembled 5762 such cases and are currently seeking additional cases meeting these criteria for second phase analyses. Conclusion Genetics of Ischaemic Stroke Functional outcome is a unique collection of ischaemic stroke cases with detailed genetic and outcome data providing an opportunity for discovery of genetic loci influencing functional outcome. Genetics of Ischaemic Stroke Functional outcome will serve as an exploratory study where the results as well as the methodological observations will provide a basis for future studies on functional outcome. Genetics of Ischaemic Stroke Functional outcome can also be used for candidate gene replication or assessing stroke outcome non-genetic association hypotheses.

Rationale No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. Aim The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation ‘spot sign’ will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4·5-hours of stroke onset compared with placebo. Design The Spot sign and Tranexamic acid On Preventing ICH growth – AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume Study outcomes The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. Discussion This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636.

Background and Purpose— Smoking may exacerbate the risk of death or further vascular events in those with stroke, but data are limited. Methods— 1589 cases of first-ever and recurrent stroke were recruited between 1996 and 1999 from a defined geographical region in North East Melbourne. Both hospital and nonhospital cases were included. Over a 10-year period, all deaths, recurrent stroke events, and acute myocardial infarctions that were reported at follow-up interviews were validated using medical records. Cox proportional hazards regression was used to assess the association between baseline smoking status (never, ex, and current) and outcome (death, acute myocardial infarction, or recurrent stroke). Results— Patients who were current smokers (Hazard Ratio [HR], 1.30; 95% Confidence Interval [CI], 1.06–1.60; P =0.012) at the time of their stroke had poorer outcome when compared with those who had never smoked. Among those who survived the first 28 days of stroke, current smokers (HR, 1.42; 95% CI, 1.13–1.78; P P =0.039) at baseline had poorer outcome than those who had never smoked. Current smokers also had a greater risk of recurrent events than past smokers (HR, 1.23; 95% CI, 1.00–1.50; P =0.050). Conclusions— Patients who smoked at the time of their stroke or had smoked before their stroke had greater risk of death or recurrent vascular events when compared with patients who were never smokers. There are benefits of smoking cessation, with ex-smokers appearing to have a lesser risk of recurrent vascular events than current smokers.

Introduction: It is uncertain why women suffer worse long-term outcomes after stroke than men. We examined sex differences in mortality and disability 1 and 5 years after stroke and identified factors contributing to these differences. Methods: Individual patient data pooling study of incident strokes (ischemic and hemorrhagic) from 1987-2013 obtained from 12 population-based cohorts from Australasia, Europe, South America and the Caribbean. Data on socio-demographics, stroke-related factors and pre-stroke health were obtained for each patient and harmonized between studies. Poisson modelling estimated the mortality rate ratio (MRR) for women compared to men at 1 year (12 studies) and 5 years (7 studies) post-stroke. Log binomial regression estimated the relative risk (RR) of poor outcome (modified Rankin scale>2 or Barthel Index Results: A total of 16557 first-ever-stroke patients with follow-up data to 1 year and 12,839 with follow-up to 5 years were included. The pooled crude mortality was greater in women than men at 1-year (MRR 1.37 95% CI 1.27-1.48) and 5 years (MRR 1.25 95% CI 1.13-1.39). However, these sex differences were reversed after adjustment for confounders at both 1 year (MRR 0.94 95% CI 0.82-1.06) and 5-years post stroke (MRR 0.74 95% CI 0.66-0.84). Similarly, the pooled crude RR for disability after stroke was greater in women than men at 1-year (RR 1.28 95% CI 1.17-1.39 and 5-year (RR 1.32 95% CI 1.18-1.47), but these sex differences disappeared after adjustment at both 1 year (RR 1.08 95%CI 0.98-1.18) and 5-years post stroke (RR 1.08 95% CI 0.97-1.20). The key contributors to worse outcomes in women were greater age, pre-stroke dependency, severe strokes and atrial fibrillation (AF, mortality only) compared with men. Conclusion: Worse outcomes in women were mostly due to age and potentially modifiable factors of stroke severity and AF providing potential targets to reduce the impact of stroke in women.

PURPOSE There has been little exploration of the distinct trajectories of psycho- logical distress after stroke and the factors that predict recovery from distress. These trajectories may assist primary care physicians by providing insight into disease onset, progression, and resolution and may be a useful way to conceptu- alize and understand the pattern of psychological morbidity in stroke over time. We undertook a longitudinal qualitative study to explore poststroke psychologi- cal trajectories METHODS The primary data collection method was semistructured interviews with community-dwelling stroke survivors in metropolitan Newcastle, New South Wales, Australia. Our sample included 23 participants (12 men, 10 women; age range 37 to 94 years) discharged from a tertiary referral hospital after a stroke; these participants subsequently participated in a total of 106 interviews over 12 months. Qualitative outcomes were participants' perceptions at baseline, 3, 6, 9, and 12 months. Thematic saturation was achieved. RESULTS Most participants were male (54%) and had a partial anterior circula- tion infarction stroke subtype (57%). Four different longitudinal trajectories were identifi ed: resilience (n = 5); ongoing crisis (n = 5), emergent mood disturbance (n = 3), and recovery from mood disturbance (n = 10). Recovery from mood dis- turbance was facilitated by gains in independence and self-esteem and by having an internal health locus of control. CONCLUSIONS Stroke survivors experienced a variety of psychological trajecto- ries. Identifying distinct trajectories of psychological morbidity may help primary care physicians develop appropriately timed interventions to promote better mental health. Interventions require implementation over a longer duration than the current outpatient services that, in Australia, are typically provided in the fi rst few months after stroke.

To explore the experience of post-stroke fatigue in community-dwelling stroke survivors with and without post-stroke mood disturbance within one year of stroke.This was a prospective qualitative cohort study including semistructured interviews undertaken at baseline (stroke onset), 3, 6, 9 and 12 months in 23 stroke survivors; eight single interviews were held with "supplementary" participants. Qualitative data analysis involved an inductive thematic approach using a process of constant comparison.Thirty-one participants (17 men, 14 women; age range 37-94 years) took part in 122 interviews. The majority of participants was independent and experienced few major depressive symptoms. Three trajectories emerged regarding the participants' experiences of fatigue including experience of fatigue, coping strategies and knowledge.The results of this study suggest that in spite of reasonable objective physical recovery post-stroke, fatigue in community-dwelling stroke survivors may be disabling. The use of qualitative methodology was sensitive in identifying the factors that play a role in the experience of fatigue. The essential role of health professionals in this context is to provide support and education regarding fatigue and to promote participation after stroke in therapy programs. Routine practice for stroke services should include fatigue advice prior to discharge.

OBJECTIVES: Women may have poorer outcomes after stroke than men because of differences in their acute management. We examined sex differences in presentation, severity, in-hospital treatment, and early mortality in a cohort of first-ever-in-a-lifetime stroke patients. METHODS: Data were collected from May 1, 1996, to April 30, 1999, in the North East Melbourne Stroke Incidence Study. Stroke symptoms, prestroke medical history, in-hospital investigations, admission and discharge medications, initial stroke severity, and 28-day mortality were recorded. Multivariable regression was used to estimate sex differences in treatment, investigations, and 28-day mortality. RESULTS: A total of 1,316 patients were included. Women were older (mean age 76 +/- 0.6 vs 72 +/- 0.6, p < 0.01), had more severe strokes (median NIH Stroke Scale score 6 vs 5, p < 0.01), and more likely to experience loss of consciousness (31% vs 23%, p = 0.003) and incontinence (22% vs 11%, p = 0.01) than men. Women were less often on lipid-lowering therapy on admission. Echocardiography and carotid investigations were less frequently performed in women due to greater age and stroke severity. Women had greater 28-day mortality (32% vs 21%, p < 0.001) and stroke severity (44% vs 36%, p = 0.01) than men, but adjustment for age, comorbidities, and stroke severity (for mortality only) completely attenuated these associations. CONCLUSION: Sex differences seen in this study were mostly explained by women's older age, greater comorbidity, and stroke severity. The reasons for differences according to age may need further examination.

Background Specific information about the nature of recurrent events that occur after each subtype of index stroke may be useful for refining preventive therapies. We aimed to determine whether stroke recurrence rates, the pattern of subtype recurrence, and prescription of secondary prevention agents differed according to initial stroke subtype. Methods Multiple overlapping sources were used to recruit all first-ever stroke patients from a geographically defined region of Melbourne, Australia over a 3-year period from 1996 to 1999. Potential stroke recurrences (fatal and nonfatal) occurring within 2 years of the initial event were identified following patient interview and follow up of death records. Subjects were classified into the different Oxfordshire groups and the type of first-ever stroke was compared with recurrent stroke events. Results One thousand, three hundred and sixteen first-ever strokes were registered during the 3-year period (mean age 74·4 years). A total of 103 first recurrent stroke events (fatal and nonfatal) occurred among those with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) during the 2-year follow-up period. The recurrent stroke subtype was different to the index stroke subtype in most (78%) patients. People with partial anterior circulation infarct had the greatest proportion of recurrences (13%), with a third of these being the more severe total anterior circulation infarct subgroup. The relative risk of ICH after an index lacunar infarct (LACI) compared with an index non-LACI was 4·06 (95% CI 1·10–14·97, P=0·038). Prescription of secondary prevention agents was greater at 2 years after stroke than at hospital discharge, and was similar between ischemic stroke subtypes. Conclusion Approximately 9% of people with first-ever stroke suffered a recurrent event, despite many being prescribed secondary prevention agents. This has implications for the uptake of current preventive strategies and the development of new strategies. The possibility that ICH is greater among index LACI cases needs to be confirmed.

Objective:To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation.Methods:We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping.Results:We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 x 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 x 10(-20) for the CE score in MO).Conclusions:Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

Introduction: Brief cognitive tests such as the Mini-mental State Examination (MMSE) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) have been used to detect cognitive impairment and dementia in studies of stroke patients. However, there are few data on their validity for such use. We have evaluated their validity in detecting cognitive impairment not dementia (CIND) and dementia in a community-based sample of first-ever stroke patients.Methods: The standardized MMSE (S-MMSE) and the 16-item IQCODE were administered to 79 patients 1 year after a first-ever stroke. CIND and dementia were diagnosed independently using a comprehensive cognitive battery. The performances of the two tests were evaluated using receiver operating characteristic (ROC) analyses. Combined performance was evaluated when their scores were used in parallel (the “or rule”), in series (the “and rule”) or as a weighted sum (the “weighted sum rule”).Results: Both tests were extremely poor at detecting CIND individually and in combination. For dementia, at traditional cut-points, the S-MMSE (≤23) was insensitive (0.50, 95% CI 0.16–0.84) and the IQCODE (≥3.30) nonspecific (0.63, 95% CI 0.51–0.75). An acceptable balance between sensitivity and specificity was achieved for dementia using the “or rule” combination, but with only modest positive predictive value.Conclusions: The S-MMSE and the IQCODE were individually poor at detecting CIND and dementia after a nonaphasic first-ever stroke. The combination was useful in detecting dementia but it does not replace the need for detailed neuropsychological tests.

Viral encephalitis is associated with significant morbidity and mortality, particularly when appropriate management is omitted as a result of delayed diagnosis. A case of herpes simplex virus type 1 (HSV-1) encephalitis is presented, demonstrating that the presentation of confusion, speech difficulties and fever with non-specific early brain CT appearances can easily be misdiagnosed as pneumonia with stroke. This case highlights the need for increased awareness of HSV-1 encephalitis among emergency physicians and radiologists, given that the early spectrum of clinical and CT findings can mimic the more common diagnoses of sepsis and stroke.

Background and Purpose— Health-related quality of life (HRQoL) data are scarce from unselected populations. The aims were to assess HRQoL at 2 years poststroke, to identify determinants of HRQoL in stroke survivors, and to identify predictors at stroke onset of subsequent HRQoL. Methods— All first-ever cases of stroke in a population of 306 631 over a 1-year period were assessed. Stroke severity, comorbidity, and demographic information were recorded. Two-year poststroke HRQoL was assessed using the Assessment of Quality of Life (AQoL) instrument (deceased patients score=0). Handicap, disability, physical impairment, depression, anxiety, living arrangements, and recurrent stroke at 2 years were documented. If necessary, proxy assessments were obtained, except for mood. Linear regression analyses were performed to identify factors independently associated with HRQoL. Results— Of 266 incident cases alive at 2 years, 225 (85%) were assessed. The mean AQoL utility score for all survivors was 0.47 (95% CI, 0.42 to 0.52). Almost 25% of survivors had a score of ≤0.1. The independent determinants of HRQoL in survivors were handicap, physical impairment, anxiety and depression, disability, institutionalization, dementia, and age. The factors present at stroke onset that independently predicted HRQoL at 2 years poststroke were age, female sex, initial NIHSS score, neglect, and low socioeconomic status. Conclusions— A substantial proportion of stroke survivors have very poor HRQoL. Interventions targeting handicap and mood have the potential to improve HRQoL independently of physical impairment and disability.

Background and Purpose— Handicap, although more relevant to the patient than impairment or disability, has received little attention in people with stroke. The aim of this study was to identify, in an unselected population, factors determining handicap at 2 years after stroke. Methods— All first-ever cases of stroke in a population of 306 631 over a 1-year period were assessed. Stroke severity, comorbidity, and demographic information was recorded. Among survivors, 2-year poststroke handicap was assessed with the London Handicap Scale. Disability, physical impairment, depression, anxiety, living arrangements, and recurrent stroke at 2 years were documented. If necessary, proxy assessments were obtained, except for mood. Linear regression analyses were performed to identify factors independently associated with handicap. First, all assessments (proxy and nonproxy) were examined; then, the nonproxy assessments were used to examine the effects of mood. Results— Of 266 patients with incident stroke who were alive at 2 years, 226 (85%) were assessed. Significant determinants of handicap on univariable analysis were age, female sex, socioeconomic status, alcohol intake, stroke subtype, initial stroke severity; 2-year physical impairment, disability, depression and anxiety scores; institutionalization; and recurrent stroke. On multivariable analysis, the independent determinants of handicap were age and 2-year physical impairment and disability. In analysis restricted to nonproxy data, depression and anxiety were also independently associated with handicap. Conclusions— Age, concurrent disability, and physical impairment were more important determinants of handicap than other demographic factors or initial stroke severity. Because depression and anxiety were independently associated with handicap, their treatment may potentially reduce handicap in stroke patients.

Background and Purpose— Generic utility health-related quality of life instruments are useful in assessing stroke outcome because they facilitate a broader description of the disease and outcomes, allow comparisons between diseases, and can be used in cost-benefit analysis. The aim of this study was to validate the Assessment of Quality of Life (AQoL) instrument in a stroke population. Methods— Ninety-three patients recruited from the community-based North East Melbourne Stroke Incidence Study between July 13, 1996, and April 30, 1997, were interviewed 3 months after stroke. Validity of the AQoL was assessed by examining associations between the AQoL and comparator instruments: the Medical Outcomes Short-Form Health Survey (SF-36); London Handicap Scale; Barthel Index; National Institutes of Health Stroke Scale; and Irritability, Depression, Anxiety scale. Sensitivity of the AQoL was assessed by comparing AQoL scores from groups of patients categorized by severity of impairment and disability and with total anterior circulation syndrome (TACS) versus non-TACS. Predictive validity was assessed by examining the association between 3-month AQoL scores and outcomes of death or institutionalization 12 months after stroke. Results— Overall AQoL utility scores and individual dimension scores were most highly correlated with relevant scales on the comparator instruments. AQoL scores clearly differentiated between patients in categories of severity of impairment and disability and between patients with TACS and non-TACS. AQoL scores at 3 months after stroke predicted death and institutionalization at 12 months. Conclusions— The AQoL demonstrated strong psychometric properties and appears to be a valid and sensitive measure of health-related QoL after stroke.

Objectives To determine the prevalence of stroke risk factors in a general practice population and to identify pharmacotherapies currently used in management of stroke risk factors. Design Multicentre, observational study by 321 randomly selected general practitioners who each collected data on 50 consecutive patients attending their surgery. Patients and setting 16 148 patients aged 30 years or older attending general practices across Australia during 2000. Outcome measures Prevalence of hypertension, current smoking, diabetes, hypercholesterolaemia, atrial fibrillation, recent history of stroke or TIA; extent of pharmacotherapy use in risk-factor management. Results 70% of patients had one or more risk factors and 34% had two or more. Hypertension was the risk factor with greatest prevalence (44%), followed by hypercholesterolaemia (43%) and current smoking (17%). The prevalence of risk factors generally increased with age, except for current smoking, where a decrease with age was seen. The most common pharmacotherapies were cardiovascular agents, followed by antiplatelet agents. Two-thirds of patients with hypertension were taking cardiovascular drugs, most commonly angiotensin-converting enzyme inhibitors. Conclusions Stroke risk factors are highly prevalent in general practice patients and GPs are ideally placed for opportunistic case-finding. There is considerable scope for improving management of stroke risk factors. The Avoid Stroke as Soon as Possible (ASAP) general practice stroke audit provides a baseline against which progress in risk-factor management can be measured.

Background and Purpose — Knowledge of patterns of handicap after stroke and of the relationship among handicap, disability, perception of recovery, and stroke subtype is limited. The aim of this study was to assess handicap 3 and 12 months after first-ever stroke in a community-based study. Methods — All strokes occurring in a population of 133 816 people were found and assessed. Patients were classified as having cerebral infarction (CI) or intracerebral hemorrhage (ICH) according to imaging or autopsy findings. Cases of CI were categorized using the Oxfordshire stroke classification. Handicap, disability, and perception of recovery were assessed 3 and 12 months after stroke using the London Handicap Scale, Barthel Index, and the question “Have you made a complete recovery from your stroke?” The association between disability and handicap was examined using Pearson’s correlation. Differences in handicap among subtypes of CI were evaluated using one-way ANOVA. Results — There were 264 cases of CI or ICH. Of surviving patients, 113 (59%) were assessed at 3 months and 107 (64%) at 12 months. The domains of handicap most affected were physical independence and occupation. Only half the variance in handicap was due to disability. Of patients without disability, those who claimed complete recovery were less handicapped than those who claimed incomplete recovery. Patients with total anterior circulation infarction were more handicapped at 3 and 12 months than those with other subtypes of CI. Conclusions — Stroke patients were handicapped across many domains. Handicap is only partly explained by disability. Stroke subtype should be considered in the interpretation of outcome data.

Background and Purpose— Studies in rodent models suggest that upregulating angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to assess the association of plasma Angpt1 with stroke occurrence and outcome. Methods— Plasma Angpt1 was measured in 336 patients who had experienced a recent stroke and 321 healthy controls with no stroke history. Patients with stroke (n=285) were reassessed at 3 months and plasma Angpt1 concentration on admission compared between those with severe and minor disability as assessed by the modified Rankin scale. In a separate cohort of 4032 community-acquired older men prospectively followed for a minimum of 6 years, the association of plasma Angpt1 with stroke incidence was examined. Results— Median plasma Angpt1 was 3-fold lower in patients who had experienced a recent stroke (6.42, interquartile range, 4.26–9.53 compared with 17.36; interquartile range, 14.01–22.46 ng/mL; P P =0.012, and remained negatively associated with severe disability or death after adjusting for other risk factors. Plasma Angpt1 was not predictive of stroke incidence in community-dwelling older men. Conclusions— Plasma Angpt1 concentrations are low after ischemic stroke particularly in patients with poor stroke outcomes at 3 months. Interventions effective at upregulating Angpt1 could potentially improve stroke outcomes.

Summary: Purpose: To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose–positron emission tomography (FDG-PET) in refractory occipital lobe epilepsy. Methods: Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy. Results: Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies. Conclusions: Ictal SPECT can provide novel localizing data in MRI-negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.

Background Thrombolysis remains the only approved therapy for acute ischaemic stroke (AIS); however, its utilisation is reported to be low. Aims This study aimed to determine the reasons for the low utilisation of thrombolysis in clinical practice. Method Five metropolitan hospitals comprising two tertiary referral centres and three district hospitals conducted a retrospective, cross-sectional study. Researchers identified patients discharged with a principal diagnosis of AIS over a 12-month time period (July 2009-July 2010), and reviewed the medical record of systematically chosen samples. Results The research team reviewed a total of 521 records (48.8% females, mean age 74.4 ±14 years, age range 5-102 years) from the 1261 AIS patients. Sixty-nine per cent of AIS patients failed to meet eligibility criteria to receive thrombolysis because individuals arrived at the hospital later than 4.5 hours after the onset of symptoms. The factors found to be positively associated with late arrival included confusion at onset, absence of a witness at onset and waiting for improvement of symptoms. However, factors negatively associated with late arrival encompassed facial droop, slurred speech and immediately calling an ambulance. Only 14.7% of the patients arriving within 4.5 hours received thrombolysis. The main reasons for exclusion included such factors as rapidly improving symptoms (28.2%), minor symptoms (17.2%), patient receiving therapeutic anticoagulation (6.7%) and severe stroke (5.5%). Conclusion A late patient presentation represents the most significant barrier to utilising thrombolysis in the acute stroke setting. Thrombolysis continues to be currently underutilised in potentially eligible patients, and additional research is needed to identify more precise criteria for selecting patients for thrombolysis.