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Objective: To identify any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS) in the alteplase dose-arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables. Results: Of 2588 participants with available imaging and clinical data, we classified cases as definite or probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of the alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Overall, low-dose alteplase (compared to standard) had no differential effect on the functional outcome (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of ICH. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all P interaction ≥0.07). Conclusions: We found no clear evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.

ObjectiveTo determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.MethodsIn a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2–6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.ResultsOf 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2–6, adjusted odds ratio [95% confidence interval] 0.60 [0.47–0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2–6, 1.04 [0.87–1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07).ConclusionsWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of EvidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.Clinical Trial RegistrationClinicaltrials.gov identifier NCT01422616.

Abstract: The under-representation of women in clinical trials is a commonly recognized and seemingly intractable problem in many different areas of clinical medicine. Discrepancies in the enrollment of women in clinical trials raises concerns about the generalizability of trial evidence, as well as the potential for reduced access and utilization of new therapies in women. Recent studies confirm that the problem of under-enrollment of women continues to exist in stroke clinical trials, even after accounting for the sex ratio of stroke cases in the underlying population. The origins of these disparities are complex, and there remains a relative dearth of stroke studies that have examined the causes in detail. Although caution should be used when generalizing research findings from studies conducted in other medical conditions including cardiology trials, factors that contribute to lower enrollment in women include the use of specific trial eligibility criteria (eg, older age, presence of specific comorbidities), patient attitudes and beliefs (resulting in less interest and more refusals in women), and potentially implicit biases among study personnel. Beyond a general call to prioritize stroke research in this area, we also recommend the greater use of trial screening logs, the use of qualitative studies to understand patient attitudes and beliefs towards stroke research, avoiding the use of age-based exclusion criteria (eg, >80 years), and increasing the number of women who lead stroke clinical trials.

OBJECTIVE: To evaluate the impact of the Coronavirus disease of 2019 (COVID-19) pandemic on patients with migraine. METHODS: Self-reported data from a migraine tracking smartphone application, Migraine Buddy, were used. Data were collected from users who reported at least one attack in the Jan, Feb, Mar and Apr of 2018, 2019 and 2020. In addition, a survey was conducted to evaluate the impact of COVID-19 on migraine management. RESULTS: On average, data from 124,717 users per month (mean age 36.3 +/- 10.9 years and 89% female) were collected. Overall, the mean frequency of migraine headache was higher in 2020 than in 2019 and higher in 2019 than in 2018. The four commonest headache triggers in 2018, 2019 and 2020 were stress in 39.7, 38.4 and 36.1%, lack of sleep in 25, 25 and 22.8%, neck pain, 20, 20.4 and 19.3 and anxiety in 19, 18.4 and 18.4% of participants, respectively. 1689 users participated in the survey and they reported that they preferred face-to-face (54.29%) to telehealth (11.9%) consultations. CONCLUSION: An increase in migraine frequency from 2018 to 2020 was reported by the users of the mobile phone. This could reflect a real increase or change in reporting habits. Stress, lack of sleep, neck pain and anxiety were the commonest attack triggers. The frequency of these triggers decreased slightly in 2020 compared to 2019 and 2018. An increase in telehealth consultations with specialists was reported in the survey but migraine patients preferred face-to-face consultations.

Background and Aim: Women have been under-represented in clinical trials areas of cardiovascular disease but there is less certainty over the level of disparity specifically in stroke and whether there is any influence of pathological subtype, age and time. We examined the participation of women in trials according to stroke prevalence in the population. Methods: Randomized controlled trials with ≥100 participants enrolled between 1990 and 2020 identified from ClinicalTrials.gov, using keywords “stroke” and “cerebrovascular accidents”, and subsequently published (identified using PubMed, Google Scholar, and Scopus) were included. To quantify sex disparites in enrolment we calculate the participation to prevalence ratio (PPR), defined as the percentage of women participating in a trial against the prevalence of women in the disease population. Results: There were 281 stroke trials eligible for analyses with a total of 588,887 participants, of whom 37.4 % were women. Overall, women were represented at a lower proportion relative to their prevalence in the underlying population (mean PPR 0.84; 95% confidence interval [CI] (0.81 to 0.87)). The greatest differences were observed in trials of hemorrhagic stroke (PPR 0.73; 95% CI 0.71 to 0.74), trials with a mean age of participants

BACKGROUND: To inform the interpretation of dietary data in the context of sex differences in diet-disease relations, it is important to understand whether there are any sex differences in accuracy of dietary reporting.OBJECTIVE: To quantify sex differences in self-reported total energy intake (TEI) compared with a reference measure of total energy expenditure (TEE).METHODS: Six electronic databases were systematically searched for published original research articles between 1980 and April 2020. Studies were included if they were conducted in adult populations with measures for both females and males of self-reported TEI and TEE from doubly labeled water (DLW). Studies were screened and quality assessed independently by 2 authors. Random-effects meta-analyses were conducted to pool the mean differences between TEI and TEE for, and between, females and males, by method of dietary assessment.RESULTS: From 1313 identified studies, 31 met the inclusion criteria. The studies collectively included information on 4518 individuals (54% females). Dietary assessment methods included 24-h recalls (n = 12, 2 with supplemental photos of food items consumed), estimated food records (EFRs; n = 11), FFQs (n = 10), weighed food records (WFRs, n = 5), and diet histories (n = 2). Meta-analyses identified underestimation of TEI by females and males, ranging from -1318 kJ/d (95% CI: -1967, -669) for FFQ to -2650 kJ/d (95% CI: -3492, -1807) for 24-h recalls for females, and from -1764 kJ/d (95% CI: -2285, -1242) for FFQ to -3438 kJ/d (95% CI: -5382, -1494) for WFR for males. There was no difference in the level of underestimation by sex, except when using EFR, for which males underestimated energy intake more than females (by 590 kJ/d, 95% CI: 35, 1,146).CONCLUSION: Substantial underestimation of TEI across a range of dietary assessment methods was identified, similar by sex. These underestimations should be considered when assessing TEI and interpreting diet-disease relations.

BACKGROUND AND PURPOSE This was an investigation of the differential effects of early intensive versus guideline-recommended blood pressure (BP) lowering between lacunar and non-lacunar acute ischaemic stroke (AIS) in the BP arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS In 1,632 participants classified as having definite or probable lacunar (n = 454 [27.8%]) or non-lacunar AIS according to pre-specified definitions based upon clinical and adjudicated imaging findings, mean BP changes over days 0-7 were plotted, and systolic BP differences by treatment between subgroups were estimated in generalized linear models. Logistic regression models were used to estimate the BP treatment effects on 90-day outcomes (primary, an ordinal shift of modified Rankin scale scores) across lacunar and non-lacunar AIS after adjustment for baseline covariables. RESULTS Most baseline characteristics, acute BP and other management differed between lacunar and non-lacunar AIS, but mean systolic BP differences by treatment were comparable at each time point (all pinteraction > 0.12) and over 24 h post-randomization (-5.5, 95% CI -6.5, -4.4 mmHg in lacunar AIS vs. -5.6, 95% CI -6.3, -4.8 mmHg in non-lacunar AIS, pinteraction = 0.93). The neutral effect of intensive BP lowering on functional outcome and the beneficial effect on intracranial haemorrhage were similar for the two subgroups (all pinteraction > 0.19). CONCLUSIONS There were no differences in the treatment effect of early intensive versus guideline-recommended BP lowering across lacunar and non-lacunar AIS.

ObjectiveTo test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).MethodsBlinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.ConclusionsNon-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

Introduction and Aim: Internationally, women are underrepresented as leaders in major scientific organizations and conferences. We aimed to determine gender differences in leadership roles and annual scientific conferences of the Stroke Society of Australasia (SSA). Methods: In a retrospective review of SSA data (2014–2019), committee members were obtained through the SSA Web site, and moderators, speakers, and award recipients were identified from SSA annual scientific conference programs. Gender was determined by name inspection and Web search. Absolute numbers and proportions of women and men were recorded for all roles examined, overall and per year. Associations between representation of women in conferences and percentage of women in speaking roles were tested using multinomial regression. Results: Presidential leadership of the SSA was held by men in 2014–2016 and 2019 and women in 2017–2018. SSA committee membership was predominantly women (55%), being lowest (47%) in 2014 and 2019 and highest (65%) in 2017. There was a wide gender variation at scientific conferences, with 41% of keynote speakers being women overall, from 20% in 2016 to 75% in 2015. From 2014 to 2019, 55% of all speakers were women, ranging from 32% (in 2016) to 71% (in 2015). A higher percentage of women as speakers or moderators was associated with a program committee with over a third of its members composed of women (p ≤ 0.044). Conclusions: Representation of women varied from 2014 to 2019 in the SSA organization and its conferences, although men are more often elected president in the organization and women are less often keynote speakers. When more women were included in the program committee, the representation of women as speakers increased.

BackgroundThe COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly. We aimed to illustrate how the stroke services were interrupted during the pandemic in China.MethodsA 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020.ResultsA total of 415 respondents completed the online survey after informed consent was obtained. Of the respondents, 37.8%, 35.2% and 27.0% were from mild, moderate and severe epidemic areas, respectively. Overall, the proportion of severe impact (reduction >50%) on the admission of transient ischaemic stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) was 45.0%, 32.0% and 27.5%, respectively. Those numbers were 36.9%, 27.9% and 22.3%; 36.5%, 22.1% and 22.6%; and 66.4%, 47.5% and 41.1% in mild, moderate and severe epidemic areas, respectively (all p50%), as reported by 54.4% of the respondents, while thrombectomy was 39.3%. These were 44.4%, 26.3%; 44.2%, 39.4%; and 78.2%, 56.5%, in mild, moderate and severe epidemic areas, respectively (all pConclusionWe found a significant reduction of admission for all types of patients with stroke during the pandemic. Patients were less likely to receive appropriate care, for example, thrombolysis/thrombectomy, after being admitted to the hospital. Stroke service in severe COVID-19 epidemic areas, for example, Wuhan, was much more severely impacted compared with other regions in China.

Background and Purpose: The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24–2.29) and deep (OR 1.50, 95% CI: 1.03–2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty – atrophy, white matter change, and old infarcts – were significantly associated with adverse physical but not emotional HRQoL domains. Conclusions: In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL.

Background and Purpose: To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm. Methods: Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned Results: Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63–10.50]; with LVO 4.92 [0.87–27.86]; no LVO 6.16 [1.57–24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12–20.26]). Conclusions: FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

IntroductionDiet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure.Methods and analysisA comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by self-report assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality.Ethics and disseminationAll data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences.PROSPERO registration numberCRD42019131715.

Background Sex differences in the management of cardiovascular disease have been reported in secondary care. We conducted a systematic review with meta‐analysis of systematically investigated sex differences in cardiovascular medication prescription among patients at high risk or with established cardiovascular disease in primary care. Methods and Results PubMed and Embase were searched between 2000 and 2019 for observational studies reporting on the sex‐specific prevalence of aspirin, statins, and antihypertensive medication prescription, including beta blockers, calcium channel blockers, angiotensin‐converting enzyme inhibitors, and diuretics, in primary care. Random effects meta‐analysis was used to obtain pooled women‐to‐men prevalence ratios for each cardiovascular medication prescription. Metaregression models assessed the impact of age and year on the findings. A total of 43 studies were included, involving 2 264 600 participants (28% women) worldwide. Participants’ mean age ranged from 51 to 76 years. The pooled prevalence of cardiovascular medication prescription for women was 41% for aspirin, 60% for statins, and 68% for any antihypertensive medications. Corresponding rates for men were 56%, 63%, and 69% respectively. The pooled women‐to‐men prevalence ratios were 0.81 (95% CI , 0.72–0.92) for aspirin, 0.90 (95% CI , 0.85–0.95) for statins, and 1.01 (95% CI , 0.95–1.08) for any antihypertensive medications. Women were less likely to be prescribed angiotensin‐converting enzyme inhibitors (0.85; 95% CI , 0.81–0.89) but more likely with diuretics (1.27; 95% CI , 1.17–1.37). Mean age, mean age difference between the sexes, and year of study had no significant impact on findings. Conclusions Sex differences in the prescription of cardiovascular medication exist among patients at high risk or with established cardiovascular disease in primary care, with a lower prevalence of aspirin, statins, and angiotensin‐converting enzyme inhibitors prescription in women and a lower prevalence of diuretics prescription in men.

Background: Major differences between women and men exist in the clinical presentation, medical care, and prognosis and outcomes of stroke. We assessed the sex-specific association of major risk factors and the risk of incident stroke, including its major subtypes, among women and men. Methods: Between 2006-10, the UK Biobank recruited over 500,000 participants aged 40-69 years across the UK. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded among 471,971 (56% women) individuals without a history of cardiovascular disease at baseline. Cox regression models yielded adjusted hazard ratios (HRs), and women-to-men ratios of HRs (RHR), for stroke associated with seven risk factors. Results: The incidence rate per 10,000 person years was 8.66 (8.29; 9.04) in women and 13.96 (13.44; 14.50) in men for any stroke; 6.06 (5.75; 6.38) in women and 11.35 (10.88; 11.84) in men for ischaemic stroke, and 1.56 (1.41; 1.73) in women and 2.23 (2.02; 2.45) in men for haemorrhagic stroke. The magnitude of the relationship between increases in indices of blood pressure, body anthropometry, and lipid levels, diabetes mellitus, and atrial fibrillation and the risk of any stroke was similar between men and women. Hypertension (stage 2), current smoking, and a low socioeconomic status, respectively, were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26; 1.47), 1.18 (1.02; 1.36), and 1.17 (1.03; 1.33). Diabetes was associated with a higher HR of ischaemic stroke in women than men (RHR: 1.25 [1.00; 1.56]). Atrial fibrillation was associated with a higher HR of haemorrhagic stroke in women than men (RHR: 2.80 [1.07; 7.36]). The incidence of stroke was higher among men than women for all risk factors, except type 1 diabetes and atrial fibrillation (haemorrhagic stroke only). Conclusion: Several risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke in the presence of risk factors generally remains higher among men than women.

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.

IntroductionLife expectancy (LE) depends on the wider determinants of health, which have different impact in women and men. Therefore, this study aimed to investigate whether gender equality was correlated with LE in women and men.MethodsGender equality in the 27 European Union (EU) member states between 2010 and 2019 was estimated using a modified Gender Equality Index (mGEI), based on the index developed by the European Institute for Gender Equality. The correlation between this mGEI and LE and the gender gap in LE was calculated using the Spearman correlation coefficient.ResultsBetween 2010 and 2019, LE increased more for men than women, which resulted in a narrowing of the gender gap in LE in the EU. During the same period, there was an increase in gender equality, as measured by the mGEI, although with substantial heterogeneity between countries. There was a strong correlation between the mGEI and the gender gap in LE (−0.880), which was explained by a stronger correlation between the mGEI and longer LE in men than in women (0.655 vs 0.629, respectively). The domains of the mGEI most strongly associated with a narrowing of the gender gap in LE were health, money and knowledge, while power was the domain with the weakest association.ConclusionsGender equality appears to be at least as beneficial to men as women with regard to LE, thus reinforcing the key role gender equality plays in improving population health and longevity.

The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute ischaemic stroke (AIS) remains controversial, especially in Asian countries. We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA. We performed a systematic literature search across MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 22 August 2016 to identify all related studies. The outcomes were death or disability (defined by modified Rankin Scale 2–6), death, and symptomatic intracerebral haemorrhage (sICH). Where possible, data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis. We included 26 observational studies and 1 randomised controlled trial with a total of 23 210 patients. Variable doses of rtPA were used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95 to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR 1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies. Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose rtPA was not associated with lower risk of death or disability, death alone, or sICH.

Background and Purpose: Hematoma volume is a key determinant of outcome in acute intracerebral hemorrhage (ICH). We aimed to compare estimates of ICH volume between simple (ABC/2, length, width, and height) and gold standard planimetric software approaches. Methods: Data are from the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Multivariable linear regression was used to compare ICH volumes on baseline CT scans using the ABC/2, modified ABC/2 (mABC/2), and MIStar software. Other aspects of ICH morphology examined included location, irregularity, heterogeneity, intraventricular and subarachnoid hemorrhage extension (SAH) of hematoma, and associated white matter lesions and brain atrophy. Results: In 2,084 patients with manual and semiautomated measurements, median (IQR) ICH volumes for each approach were: ABC/2 11.1 (5.11–20.88 mL), mABC/2 7.8 (3.88–14.11 mL), and MIStar 10.7 (5.59–18.66 mL). Median differences between ABC/2 and MIStar, and mABC/2 and MIStar were 0.34 (–1.01 to 2.96) and –2.4 (–4.95 to –0.7416), respectively. Hematoma volumes differed significantly with irregular shape (ABC/2 and MIStar, p < 0.001; mABC/2 and MIStar, p = 0.007) and larger volumes (mABC/2 and MIStar, p < 0.001; ABC/2 and MIStar, p = 0.07). ICH with SAH showed a significant discrepancy between ABC/2 and MIStar (p < 0.001). Conclusions: Overall, ABC/2 performs better than mABC/2 in estimating ICH volume. The largest discrepancies were evidenced against automated software for irregular-shaped and large ICH with SAH, but the clinical significance of this is uncertain.

ObjectiveTo explore the sex differences in outcomes and management after stroke using a large sample with high-quality international trial data.MethodsIndividual participant data were obtained from 5 acute stroke randomized controlled trials. Data were obtained on demographics, medication use, in-hospital treatment, and functional outcome. Study-specific crude and adjusted models were used to estimate sex differences in outcomes and management, and then pooled using random-effects meta-analysis.ResultsThere were 19,652 participants, of whom 7,721 (40%) were women. After multivariable adjustments, women with ischemic stroke had higher survival at 3–6 months (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70–0.97), higher likelihood of disability (OR 1.20, 95% CI 1.06–1.36), and worse quality of life (weighted mean difference −0.07, 95% CI −0.09 to 0.04). For management, women were more likely to be admitted to an acute stroke unit (OR 1.17, 95% CI 1.01–1.34), but less likely to be intubated (OR 0.58, 95% CI 0.36–0.93), treated for fever (OR 0.82, 95% CI 0.70–0.95), or admitted to an intensive care unit (OR 0.83, 95% CI 0.74–0.93). For preadmission medications, women had higher odds of being prescribed antihypertensive agents (OR 1.22, 95% CI 1.13–1.31) and lower odds of being prescribed antiplatelets (OR 0.86, 95% CI 0.79–0.93), glucose-lowering agents (OR 0.86, 95% CI 0.78–0.94), or lipid-lowering agents (OR 0.85, 95% CI 0.77–0.94).ConclusionsThis analysis suggests that women who had ischemic stroke had better survival but were also more disabled and had poorer quality of life. Variations in hospital and out-of-hospital management may partly explain the disparities.

Objectives Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk–benefit balance of low-dose alteplase treatment. Methods Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Results Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Conclusion Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.

OBJECTIVE: We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres. METHODS: The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were based upon estimated catchment populations. RESULTS: On thousand, five hundred and fifty-five patients from 76 centres were included, mostly from centres that specialize in hypertension (55%), cardiology (11%) or nephrology (19%). Mean age was 64, 60% were men, 62% were Caucasian, 36% had chronic kidney disease, 41% had diabetes, 12% were smokers and 31% had a previous cardiovascular event. Daytime and night-time ambulatory blood pressure (BP) was the most frequently used measurement for diagnosis (82%). Ninety-five percent of patients were prescribed diuretics, 93% an inhibitor of the renin-angiotensin system, 86% a calcium channel blocker, 74% a beta-blocker and 36% an aldosterone antagonist. The overall estimated mean incidence of TRH was 5.8 per 100 000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100 000 (ranging between 7.6 and 90.5 across regions). CONCLUSION: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patient selection and errors in estimation of catchment population across participating centres.

Background Understanding of sex differences, especially in terms of the influence of sex on therapeutic interventions, can lead to improved treatment and management for all. Aim We examined temporal and regional trends in female participation and the reporting of sex differences in stroke randomized controlled trials. Methods Randomized controlled trials from 1990 to 2018 were identified from ClinicalTrials.gov, using keywords “stroke” and “cerebrovascular accidents.” Studies were selected if they enrolled ≥100 participants, included both sexes and were published trials (identified using PubMed, Google Scholar, and Scopus). Results Of 1700 stroke randomized controlled trials identified, 277 were published and eligible for analysis. Overall, these randomized controlled trials enrolled only 40% females, and in the past 10 years, this percentage barely changed, peaking at 41% in 2008–2009 and 2012–2013. North American randomized controlled trials recruited the most women, at 43%, and Asia the lowest, at 40%. Among the 277 randomized controlled trials, 101 (36%) reported results according to sex, of which 91 (33%) were pre-specified analyses. The increasing trend in the number of studies reporting sex-differentiated results from 2008 to 2018 merely paralleled the increase in the number of papers published during the same time period. North American randomized controlled trials most often reported sex-specific results (42%), and Australia and Europe least often (31%). Conclusion Little progress has been made in the inclusion of females and the reporting of sex in stroke randomized controlled trials. This highlights the need for key stakeholders, such as funders and journal editors, to provide clear guidance and effective implementation strategies to researchers in the scientific reporting of sex.

Introduction: Early recurrence of acute ischemic stroke (AIS) predicts adverse outcome, but there is uncertainty about the predictors after intravenous alteplase. We aimed to determine the predictors of stroke/transient ischemic attack (TIA) and their prognostic significance among ENCHANTED participants. Methods: ENCHANTED was an international, randomized, open-label, blinded-endpoint trial of low- versus standard-dose intravenous alteplase in AIS patients. Log-rank test and multivariable analysis with cox-regression models were used to assess the association of baseline characteristics and stroke/TIA recurrence and of functional outcome (modified Rankin scale [mRS] scores 2-6) at 90 days. Results: Among 3297 AIS participants, 103 (3%) had early recurrent AIS/TIA, which was predicted by recruitment in South America (hazard ratio 1.75, 95%CI 1.04-2.94), history of coronary artery disease (1.67, 1.03-2.72) and extra/intra-cranial vessel stenosis (2.94, 1.49-5.81), premorbid mRS ≥1 (1.63, 1.04-2.55), lipid lowering therapy (1.66, 1.03-2.67), multiple ischemic brain imaging lesions (2.33, 1.50-3.61), and cardioembolic stroke (1.58, 1.02-2.46). Early recurrence was independently associated with poor functional outcome (odds ratio 4.76, 95%CI 2.63-8.42). Conclusions: After treatment with intravenous alteplase, early recurrence of cerebral ischemic events complicates recovery and residual disability. Better targeting of preventive strategies in those at high risk, specifically those with cardioatherosclerosis and cardioembolic disease, may improve outcome from AIS.

Background and purpose: An early elevation in blood pressure (BP) is common after spontaneous intracerebral hemorrhage (ICH), has various potential causes, and is predictive of poor outcome. We aimed to determine the predictors of this phenomenon, in pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials [INTERACT1 (n = 404) and INTERACT2 (n = 2829)]. Methods: INTERACT trials were international, open, blinded endpoint, randomized controlled trials of patients with spontaneous ICH (Results: Among 3233 patients (mean age 63 years; 37% female; baseline mean SBP 179 mmHg), both analytic approaches showed significant positive associations of high admission BP with history of hypertension, admission hyperglycemia at least 6.5 mmol/l, elevated heart rate, and greater neurological severity (National Institutes of Health Stroke Scale scores); and significant negative associations with prior use of antithrombotic agents and longer time from onset to randomization. Conclusion: The high admission BP of mild-to-moderate acute ICH is related to autonomic nervous system activated ‘stress’ rather than hematoma location and mass effect.

Previous studies consistently reported a diurnal variation in the occurrence of intracerebral hemorrhage (ICH), with a morning peak. However, limited knowledge exists on the circadian pattern of ICH severity and outcome. This study aimed to determine possible associations between ICH onset time and admission severity and 90-day outcomes using the combined data set of the pilot and main-phase Intensive blood pressure (BP) reduction in an acute cerebral hemorrhage trial (INTERACT). The ICH onset time was categorized into three groups (1: 00:00-07:59; 2: 08:00-15:59; and 3: 16:00-23:59). We found an association between onset time and low Glasgow Coma Scale score: aOR (time 1: 1.72, 95% CI 1.12-2.66; time 3: 1.95, 95% CI 1.31-2.89, p = 0.003; in comparison to time 2). There was no association between onset time and volume of ICH (adjusted p = 0.354) or 90-day outcomes of death or major disability, and death and major disability separately (all adjusted p > 0.4). The results showed that more severe cases of ICH patients, defined by a reduced level of consciousness, had late afternoon to early morning stroke onset, but this was unrelated to baseline hematoma volume or location. There was no circadian influence on ICH clinical outcome.

The authors thank Drs. Ganesh and Varma for their interest in our article.1 We agree with Drs. Ganesh and Varma's comments on premorbid disability potentially influencing the sex differences in 90-day mRS. Indeed, the findings from the INternational STRoke oUtComes sTudy (INSTRUCT),2 which was individual participant data (IPD) for incident strokes obtained from 13 population-based incidence studies, showed that prestroke functional limitation was one of the confounding factors—along with age, stroke severity, and history of atrial fibrillation—that reversed the greater mortality in women compared with men after adjustments.

For the most part, stroke is a disease of old age. With the predicted increase in the aged population and longer life expectancies, the number and proportion of people living with stroke is expected to increase, especially among women and the elderly. For those who suffer stroke, there is a high likelihood of experiencing death and severe disability. Therefore, the issue of stroke amongst women (and men) is a key priority in global public health. In this review, we consider sex and gender differences in ischemic and hemorrhagic stroke, and we summarize data that outlines the epidemiology, risk factor, treatment recovery and prevention of stroke. We discuss possible mechanisms for the sex differences, specifically in areas of biology, medical management and social and behavioral context. With evidence showing that women and men experience stroke differently, sex must be taken into account when treating patients and when designing clinical trials.

Summary box Despite some progress over the last decade, gender inequalities persist in academic and research settings. Previous studies have shown that women have a lesser share of authorship positions overall and are less likely than men to be first or last author, the most relevant positions to career progression.1 The gap between total authorships for women and men has been stable in recent years, but has grown for senior authorships.2 With lockdowns enforced across the globe due to the COVID-19 pandemic, many researchers are now working from home and face competing demands from parenting, homeschooling and other caring duties. These roles are predominantly assumed by women, especially in countries with high gender inequality. Women’s representation in research generally, and specifically in the study of COVID-19, may be disproportionately affected by lockdown measures. Under-representation of female researchers tends to create under-representation of issues that are relevant to women in research — in our current situation this may create important gaps in our understanding of COVID-19. Therefore, we investigated whether gender differences existed in authorship of COVID-19 research since the onset of the pandemic. …

Background: While returning to paid work is a crucial marker of stroke recovery, little is known about the differences in unpaid work by sex following stroke. We aimed to determine the sex differences in participation in unpaid work 12 months after stroke. Methods: Psychosocial outcomes in stroke were a prospective, multicentre observational study that recruited individuals, 18–64 years, within 28 days of stroke from New South Wales, Australia. Unpaid work was defined as ≥5 h per week of one or more of: unpaid domestic work for the household; unpaid care of others; looking after own children without pay or looking after someone else’s children without pay. Data was collected before stroke, 28 days (baseline), 6 and 12 months follow-up. Results: Eighty per cent of women and 52% of men engaged in ≥5 h per week of unpaid work before stroke. At 12 months after, 69% of women and 53% of men completed ≥5 h of unpaid work per week. For women, there was a significant association between participation in unpaid work at 12 months and having financially dependent children (OR 2.67; 95% CI 1.08–6.59). A return to unpaid work in men was associated with participation in unpaid work before stroke (OR 3.74; 95% CI 2.14–6.53). Conclusions: More women are engaged in unpaid work before and at 12 months after stroke, but there is a reduction in the proportion of women returning to unpaid work at 12 months not seen in men. Consideration may need to be given to the development of rehabilitation strategies targeted at the specific needs of stroke survivors.

Objective To determine the adverse outcomes following resumption of anticoagulation in patients with anticoagulation-associated intracranial haemorrhage (ICH). Design We performed a systematic review and meta-analysis in this clinical population. The Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement was followed, and two authors independently assessed eligibility of all retrieved studies and extracted data. Data sources Medline, Embase and the Cochrane Central Register of Controlled Trials, from inception to February 2017. Eligibility criteria and outcomes Randomised controlled trials or cohort studies that recruited adults who received oral anticoagulants at the time of ICH occurrence and survived after the acute phase or hospitalisation were searched. Primary outcomes, including long-term mortality, recurrent ICH and thromboembolic events. Secondary outcomes were the frequency of resuming anticoagulant therapy and related factors. Results We included 12 cohort studies (no clinical trials) involving 3431 ICH participants. The pooled frequency of resuming anticoagulant therapy was 38% (95% CI 32% to 44%), but this was higher in participants with prosthetic heart valves, subarachnoid haemorrhage or dyslipidaemia. There was no evidence that resuming anticoagulant therapy was associated with higher long-term mortality (pooled relative risk (RR) 0.60, 95% CI 0.30 to 1.19; p=0.14) or ICH recurrence (pooled RR 1.14, 95% CI 0.72 to 1.80; p=0.57). Resumption of anticoagulation was associated with significantly fewer thromboembolic events (pooled RR 0.31, 95% CI 0.23 to 0.42; p

ObjectiveTo determine the optimal cut point on the NIH Stroke Scale (NIHSS) for predicting poor 90-day clinical outcome in patients with supratentorial and infratentorial acute ischemic stroke (AIS).MethodsData are from participants of the alteplase-dose arm of the randomized controlled trial, Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Associations between baseline characteristics of clinically defined supratentorial and infratentorial AIS patients and poor functional outcome, defined by scores 3–6 on the modified Rankin Scale, were evaluated in logistic regression models, with area under the curve (AUC) receiver operating characteristics defining the optimal NIHSS predictor cut point.ResultsPatients with infratentorial AIS (n = 289) had lower baseline NIHSS scores than those with supratentorial AIS (n = 2,613) (median 7 vs 9; p < 0.001). NIHSS cut points for poor outcome were 10 (AUC 76, sensitivity 65%, specificity 73%) and 6 (AUC 69, sensitivity 72%, specificity 56%) in supratentorial and infratentorial AIS, respectively. There was no significant difference in functional outcome or symptomatic intracranial hemorrhage between AIS types.ConclusionsIn thrombolysis-eligible AIS patients, the NIHSS may underestimate clinical severity for infratentorial compared to supratentorial lesions for a similar prognosis for recovery. Because thrombolysis treatment has low effect on stroke outcome in patients with infratentorial AIS when baseline NIHSS score is more than 6, additional treatment such as endovascular treatment should be considered to improve stroke outcome.Clinicaltrials.gov identifierNCT01422616.

Background and Purpose— Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2). Methods— INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], Results— Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for P trend6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). Conclusions— Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Background and Purpose— Clinical utility of electronic Alberta Stroke Program Early CT Score (e-ASPECTS), an automated system for quantifying signs of infarction, was evaluated in a large database of thrombolyzed patients with acute ischemic stroke. Methods— All baseline noncontrast computed tomographic scans of patients with anterior circulation acute ischemic stroke who participated in the alteplase dose arm of the randomized controlled trial ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) were reviewed; poor quality and large (>6 mm) slice thickness were excluded. Included scans had e-ASPECTS scores correlated with baseline neurological severity (National Institutes of Health Stroke Scale scores) and 90-day disability outcomes (modified Rankin Scale scores). Multivariable logistic regression models were used to determine the predictive ability of e-ASPECTS for disability outcomes and symptomatic intracranial hemorrhage. Results— Of 2426 available computed tomographic images, 1480 (61%) were included in analyses of e-ASPECTS scores (median 9 [interquartile range, 8–10], 77% with good [range, 8–10] scores). Lower e-ASPECTS scores (per 1-point decrease) were significantly associated with increasing baseline National Institutes of Health Stroke Scale scores ( r , −0.31; P r , −0.27; P Conclusions— e-ASPECT scores from thin computed tomographic slices (≤6 mm) were highly correlated with baseline neurological severity and independently predict functional recovery and adverse outcomes in acute ischemic stroke. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Purpose To determine the frequency of false positive diagnoses of epilepsy and to explore its imitators and consequences. Method A systematic review of all published observational studies (to November 2015) was conducted to determine the proportion of false positive diagnoses of epilepsy. We included studies of people of all ages receiving a diagnosis of epilepsy. All observational study designs were included with the exception of case-reports and case series with fewer than 3 participants. Results Data were available from 27 studies (31 reports), reporting considerably varied frequencies of false positive diagnoses. The frequency of false positive diagnosis range from 2% to 71%. The data also suggest that syncope and psychogenic non-epileptic paroxysmal events were the commonest imitators of epilepsy. Misdiagnosis led to mismanagement with anti-epileptic drugs (AEDs) and affected legal driving status and employment. Conclusions False positive diagnosis of epilepsy is common, even though there is considerable heterogeneity across studies. All potential imitators should be considered and clinicians should be cautious introducing AEDs without a definite diagnosis given the risk of side effects, and the possible impact on legal driving status and employment.

Non-traumatic intracranial hemorrhage (i.e. intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) are more life threatening and least treatable despite being less common than ischemic stroke. Elevated blood pressure (BP) is a strong predictor of poor outcome in both ICH and SAH. Data from a landmark clinical trial INTERACT 2, wherein 2839 participants enrolled with spontaneous ICH were randomly assigned to receive intensive (target systolic BP

Background and Aim: There is little evidence on the prognostic significance of hyponatremia in patients with intracerebral hemorrhage (ICH). The aim of this study was to clarify the association of hyponatremia with clinical outcomes and to determine the relationship between hyponatremia and hematoma and perihematomal edema growth. Methods: This study was a subsidiary, post-hoc analysis of INTERACT 1 and 2; which were randomised controlled trials of patients with acute spontaneous ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP < 140 mmHg) or guideline-based (< 180 mmHg) BP management. Hyponatremia was defined as serum sodium < 135 mEq/L. The primary clinical outcome was death at 90 days. The outcomes of the CT substudies were absolute growth of hematoma and perihematomal edema volume in 24 hours. Results: Among 3002 patients with information on sodium and clinical outcomes, 349 (12%) had hyponatremia, which was associated with death at 90 days (multivariable-adjusted OR, 2.03; 95% CI, 1.41-2.91; p=0.0001). In the hematoma growth and perihematomal edema growth analyses, there were 1241 and 790 patients included, respectively. No associations were observed for hematoma growth or perihematomal edema growth during the first 24 hours. Conclusions: Hyponatremia is associated with higher mortality at 90 days in patients with spontaneous ICH. Hyponatremia does not appear to affect perihematomal edema growth or hematoma volume growth.

Item does not contain fulltext OBJECTIVES: To determine the association of hyponatremia at presentation with clinical and imaging outcomes in patients with acute intracerebral hemorrhage. DESIGN: Retrospective pooled analysis of prospectively collected data from 3,243 participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (international, multicenter, open, blinded endpoint, randomized controlled trials designed to assess the effects of early intensive blood pressure lowering in patients with acute intracerebral hemorrhage). SETTING: Clinical hospital sites in 21 countries. PATIENTS: Patients with predominantly mild-moderate severity of spontaneous intracerebral hemorrhage within 6 hours of onset and elevated systolic blood pressure (150-220 mm Hg) were included in the study. INTERVENTIONS: Patients were assigned to receive intensive (target systolic blood pressure, < 140 mm Hg within 1 hr) or guideline-recommended (target systolic blood pressure, < 180 mm Hg) blood pressure-lowering therapy. MEASUREMENTS AND MAIN RESULTS: Presentation hyponatremia was defined as serum sodium less than 135 mEq/L. The primary outcome was death at 90 days. Multivariable logistic regression was used to assess the association of hyponatremia with important clinical events. Of 3,002 patients with available data, 349 (12%) had hyponatremia. Hyponatremia was associated with death (18% vs 11%; multivariable-adjusted odds ratio, 1.81; 95% CI, 1.28-2.57; p < 0.001) and larger baseline intracerebral hemorrhage volume (multivariable adjusted, p = 0.046) but not with baseline perihematomal edema volume nor with growth of intracerebral hemorrhage or perihematomal edema during the initial 24 hours. CONCLUSIONS: Hyponatremia at presentation is associated with increased mortality in patients with predominantly deep and modest volume intracerebral hemorrhage through mechanisms that seem independent of growth in intracerebral hemorrhage or perihematomal edema.

Background and Purpose— Faster heart rate predicts higher mortality in coronary heart disease and acute ischemic stroke, but its prognostic significance in intracerebral hemorrhage remains uncertain. We aimed to determine the effect of admission heart rate on clinical and imaging outcomes in patients with intracerebral hemorrhage. Methods— A post hoc pooled analysis of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT 1 and 2). Clinical outcomes were mortality and modified Rankin Scale score at 90 days; and imaging outcome was absolute growth in hematoma volume during the initial 24 hours. Patients were divided into 4 categories according to baseline heart rate ( Results— Of 3185 patients with available data, higher admission heart rate was associated with both mortality and worse modified Rankin Scale score: adjusted hazard ratio for heart rate (≥85 versus P -trend P -trend, 0.196). Conclusions— Higher admission heart rate is independently associated with death and poor functional outcome after acute intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00226096 and NCT00716079.

Elevated blood pressure (BP), which presents in approximately 80 % of patients with acute intracerebral hemorrhage (ICH), is associated with increased risk of poor outcome. The Second Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) study, a multinational, multicenter, randomized controlled trial published in 2013, demonstrated better functional outcomes with no harm for patients with acute spontaneous ICH within 6 h of onset who received target-driven, early intensive BP lowering (systolic BP target

Intraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2).Pooled analyses of the INTERACT CT substudies-international, multicentre, prospective, open, blinded end point, randomised controlled trials of patients with acute spontaneous ICH and elevated systolic blood pressure (SBP)-randomly assigned to intensive (140 mm Hg) or guideline-based (180 mm Hg) SBP management. Participants had blinded central analyses of baseline and 24 h CTs, with dIVH defined as new intraventricular haemorrhage (IVH) on the latter scan. Outcomes of death and major disability were defined by modified Rankin Scale scores at 90 days.There were 349 (27%) of 1310 patients with baseline IVH, and 107 (11%) of 961 initially IVH-free patients who developed dIVH. Significant associations of dIVH were prior warfarin anticoagulation, high (≥15) baseline National Institutes of Health Stroke Scale score, larger (≥15 mL) ICH volume, greater ICH growth and higher achieved SBP over 24 h. Compared with those who were IVH-free, dIVH had greater odds of 90-day death or major disability versus initial IVH (adjusted ORs 2.84 (95% CI 1.52 to 5.28) and 1.87 (1.36 to 2.56), respectively (p trend0.0001)).Although linked to factors determining greater ICH growth including poor SBP control, dIVH is independently associated with poor outcome in acute small to moderate-size ICH.NCT00226096 and NCT00716079.

Whether there are any benefits without harm from early lowering of blood pressure (BP) in the setting of acute ischemic stroke (AIS) has been a longstanding controversy in medicine. Whilst most studies have consistently shown associations between elevated BP, particularly systolic BP, and poor outcome, some also report that very low BP (systolic

A 48-year old man presented with a 20-year history of neurological symptoms. He reported slowly progressive changes in gait, mild right leg weakness and subtle short-term memory problems. There was no history of discrete relapses and no family history of neurological disease. The neurological examination revealed upper and lower limb weakness, marked lower limb spasticity, globally brisk reflexes and extensor plantar responses. MRI of the brain demonstrated white matter T2/FLAIR hyperintensities with extensive pericallosal involvement and MRI of the spinal cord revealed lesions in the thoracic cord suggestive of demyelination. Somatosensory and visual evoked potentials were markedly delayed and oligoclonal bands were detected in cerebrospinal fluid, consistent with multiple sclerosis. Nerve conduction studies demonstrated electrophysiological evidence of a generalised demyelinating, sensorimotor neuropathy, without temporal dispersion or conduction block, suggestive of an inherited cause. Genetic testing revealed PMP22 duplication, confirming Charcot-Marie-Tooth disease type 1A. This case highlights the rare co-existence of acquired central demyelination (i.e. primary progressive MS) in conjunction with inherited peripheral demyelination (CMT 1A).