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.

Objectives Since liver transplant (LT) was introduced to treat patients with familial amyloid polyneuropathy carrying the V30M mutation (ATTR-V30M), ocular and cardiac complications have developed. Long-term central nervous system (CNS) involvement was not investigated. Our goals were to: (1) identify and characterise focal neurological episodes (FNEs) due to CNS dysfunction in ATTR-V30M patients; (2) characterise neuropathological features and temporal profile of CNS transthyretin amyloidosis. Methods We monitored the presence and type of FNEs in 87 consecutive ATTR-V30M and 35 non-ATTR LT patients. FNEs were investigated with CT scan, EEG and extensive neurovascular workup. MRI studies were not performed because all patients had cardiac pacemakers as part of the LT protocol. We characterised transthyretin amyloid deposition in the brains of seven ATTR-V30M patients, dead 3–13 years after polyneuropathy onset. Results FNEs occurred in 31% (27/87) of ATTR-V30M and in 5.7% (2/35) of the non-ATTR transplanted patients (OR=7.0, 95% CI 1.5 to 33.5). FNEs occurred on average 14.6 years after disease onset (95% CI 13.3 to 16.0) in ATTR-V30M patients, which is beyond the life expectancy of non-transplanted ATTR-V30M patients (10.9, 95% CI 10.5 to 11.3). ATTR-V30M patients with FNEs had longer disease duration (OR=1.24; 95% CI 1.07 to 1.43), renal dysfunction (OR=4.65; 95% CI 1.20 to 18.05) and were men (OR=3.57; 95% CI 1.02 to 12.30). CNS transthyretin amyloidosis was already present 3 years after polyneuropathy onset and progressed from the meninges and its vessels towards meningocortical vessels and the superficial brain parenchyma, as disease duration increased. Conclusions Our findings indicate that CNS clinical involvement occurs in ATTR-V30M patients regardless of LT. Longer disease duration after LT can provide the necessary time for transthyretin amyloidosis to progress until it becomes clinically relevant. Highly sensitive imaging methods are needed to identify and monitor brain ATTR. Disease modifying therapies should consider brain TTR as a target.

Background and Purpose— Mortality statistics indicate that Portugal has the highest stroke mortality in Western Europe. Data on stroke incidence in Northern Portugal, the region with the highest mortality, are lacking. This study was designed to determine stroke incidence and case fatality in rural and urban populations in Northern Portugal. Methods— All suspected first-ever-in-a-lifetime strokes occurring between October 1998 and September 2000 in 37 290 residents in rural municipalities and 86 023 living in the city of Porto were entered in a population-based registry. Standard definitions and comprehensive sources of information were used for identification of patients who were followed-up at 3 and 12 months after onset of symptoms. Results— During a 24-month period, 688 patients with a first-ever stroke were registered, 226 in rural and 462 in urban areas. The crude annual incidence was 3.05 (95% CI, 2.65 to 3.44) and 2.69 per 1000 (95% CI, 2.44 to 2.93) for rural and urban populations, respectively; the corresponding rates adjusted to the European standard population were 2.02 (95% CI, 1.69 to 2.34) and 1.73 (95% CI, 1.53 to 1.92). Age-specific incidence followed different patterns in rural and urban populations, reaching major discrepancy for those 75 to 84 years old, 20.2 (95% CI, 16.1 to 25.0) and 10.9 (95% CI, 9.0 to 12.8), respectively. Case fatality at 28 days was 14.6% (95% CI, 10.2 to 19.3) in rural and 16.9% (95% CI, 13.7 to 20.6) in urban areas. Conclusions— Stroke incidence in rural and urban Northern Portugal is high compared to that reported in other Western Europe regions. The high official mortality in our country, which could be explained by a relatively high incidence, was not because of a high case fatality rate.

Background: Changes in meteorological parameters have been associated with cardiovascular mortality and stroke. The high incidence of stroke in Portugal may be modelled by short- or long-term weather changes whose effect may be different across stroke types and severity. Methods: Data include all patients with a first-ever-in-a-lifetime stroke registered in a population of 86,023 residents in the city of Porto from October 1998 to September 2000. Specific stroke types were considered and ischaemic stroke (IS) subtype was defined according to the Oxfordshire Community Stroke Projet classification and the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Information on daily temperature, humidity and air pressure was obtained from the National Meteorological Office. The Poisson distribution was used to model the daily number of events as a function of each weather parameter measured over different hazard periods, and the binomial model to contrast effects across subgroups. Differential effects of meteorological parameters and hazard periods upon stroke occurrence and outcome were analysed in a stepwise model. Results: Among the 462 patients registered, 19.6% had a primary intracerebral haemorrhage (PICH) and 75.3% an IS. Among patients with IS, 21.6% were total anterior circulation infarcts (TACIs), 19.8% partial anterior circulation infarcts (PACIs), 19.5% posterior circulation infarcts (POCIs) and 39.1% were lacunar infarcts (LACIs). The aetiology of IS was large artery atherosclerosis in 6.9%, cardioembolism in 23.3% and small artery occlusion in 35.6%. The incidence of PICH increased by 11.8% (95% CI: 3.8–20.4%) for each degree drop in the diurnal temperature range in the preceding day. The incidence of IS increased by 3.9% (95% CI: 1.6–6.3%) and cardioembolic IS by 5.0% (95% CI: 0.2–10.1%) for a 1°C drop in minimum temperature in the same hazard period. The incidence of TACIs followed the IS pattern while for PACIs and POCIs there were stronger effects of longer hazard periods and no association was found for LACIs. The relative risk of a fatal versus a non-fatal stroke increased by 15.5% (95% CI: 6.1–25.4%) for a 1°C drop in maximum temperature over the previous day. Conclusions: Outdoor temperature and related meteorological parameters are associated with stroke occurrence and severity. The different hazard periods for temperature effects and the absence of association with LACIs may explain the heterogeneous effects of weather on stroke occurrence found in community-based and hospital admission studies. Emergency services should be aware that specific weather conditions are more likely to prompt calls for more severe strokes.

Objective To examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke. Methods Individual 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 <20) at 1 year (10 studies, n = 4,852) and 5 years (7 studies, n = 2,226). Multivariable linear regression was used to compare the mean difference (MD) in participation restriction by use of the London Handicap Scale (range 0–100 with lower scores indicating poorer outcome) for women compared to men at 5 years (2 studies, n = 617). For each outcome, study-specific estimates adjusted for confounding factors (e.g., sociodemographics, stroke-related factors) were combined with the use of random-effects meta-analysis. Results In unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RR_unadjusted 1.32, 95% confidence interval [CI] 1.18–1.48; 5 years: RR_unadjusted 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: RR_adjusted 1.08, 95% CI 0.97–1.20; 5 years: RR_adjusted 1.05, 95% CI 0.94–1.18). Women also had greater participation restriction than men (pooled MD_unadjusted −5.55, 95% CI −8.47 to −2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MD_adjusted −2.48, 95% CI −4.99 to 0.03). Conclusions Worse 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.

Background: Transthyretin amyloidosis due to V30M mutation (ATTR-V30M) is the most frequent hereditary ATTR amyloidosis. Besides neurophysiological measures, there are no biomarkers to detect preclinical disease or monitor disease progression. CSF or plasma neurofilament light chain (pNfL) have recently been considered sensitive biomarkers to quantitate neuro-axonal damage in several disorders of the peripheral and central nervous system. Objective: Characterise plasma NfL levels in a series of untreated ATTR-V30M patients stratified by clinical severity using a cross-sectional retrospective study design. Methods: Sixty ATTR-V30M patients and 16 controls from 2 independent cohorts were analysed for pNfL by single-molecule array assay (SIMOA) technique. Disease severity was assessed with Polyneuropathy Disability Score. Results: pNfL is elevated in ATTR-V30M patients as a function of disease severity in both cohorts. Moreover, pNfL discriminates asymptomatic mutation carriers from early symptomatic patients (AUC = 0.97; p < .001) with high sensitivity (92.3%) and specificity (93.8%). pNfL elevation (>66.9 pg/mL) also discriminates patients with sensory neuropathy from patients with motor neuropathy (AUC = 0.91; p < .01) with a sensitivity of 61.5% and a specificity of 92.3%. Conclusion: pNfL is an easily accessible biomarker to establish ATTR-V30M disease conversion and to monitor disease progression. pNfL could be used as efficacy measure of disease-oriented therapies in clinical and pre-clinical trials.