Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke

Sex-specific lesion pattern of functional outcomes after stroke.

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke.

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health

Global and regional ecological boundaries explain abrupt spatial discontinuities in avian frugivory interactions

Species interactions can propagate disturbances across space via direct and indirect effects, potentially connecting species at a global scale. However, ecological and biogeographic boundaries may mitigate this spread by demarcating the limits of ecological networks. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among plant-frugivore networks, while accounting for background spatial and elevational gradients and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1496 plant and 1004 bird species) distributed across 67 ecoregions, 11 biomes, and 6 continents. We show that dissimilarities in species and interaction composition, but not network structure, are greater across ecoregion and biome boundaries and along different levels of human disturbance. Our findings indicate that biogeographic boundaries delineate the world’s biodiversity of interactions and likely contribute to mitigating the propagation of disturbances at large spatial scales.The authors acknowledge the following funding: University of Canterbury Doctoral Scholarship (L.P.M.); The Marsden Fund grant UOC1705 (J.M.T., L.P.M.); The São Paulo Research Foundation - FAPESP 2014/01986-0 (M.G., C.E.), 2015/15172-7 and 2016/18355-8 (C.E.), 2004/00810-3 and 2008/10154-7 (C.I.D., M.G., M.A.P.); Earthwatch Institute and Conservation International for financial support (C.I.D., M.G., M.A.P.); Carlos Chagas Filho Foundation for Supporting Research in the Rio de Janeiro State – FAPERJ grant E-26/200.610/2022 (C.E.); Brazilian Research Council grants 540481/01-7 and 304742/2019-8 (M.A.P.) and 300970/2015-3 (M.G.); Rufford Small Grants for Nature Conservation No. 22426–1 (J.C.M., I.M.), No. 9163-1 (G.B.J.) and No. 11042-1 (MCM); Universidade Estadual de Santa Cruz (Propp-UESC; No. 00220.1100.1644/10-2018) (J.C.M., I.M.); Fundação de Amparo à Pesquisa do Estado da Bahia - FAPESB (No. 0525/2016) (J.C.M., I.M.); European Research Council under the European Union’s Horizon 2020 research and innovation program (grant 787638) and The Swiss National Science Foundation (grant 173342), both awarded to C. Graham (D.M.D.); ARC SRIEAS grant SR200100005 Securing Antarctica’s Environmental Future (D.M.D.); German Science Foundation—Deutsche Forschungsgemeinschaft PAK 825/1 and FOR 2730 (K.B.G., E.L.N., M.Q., V.S., M.S.), FOR 1246 (K.B.G., M.S., M.G.R.V.) and HE2041/20-1 (F.S., M.S.); Portuguese Foundation for Science and Technology - FCT/MCTES contract CEECIND/00135/2017 and grant UID/BIA/04004/2020 (S.T.) and contract CEECIND/02064/2017 (L.P.S.); National Scientific and Technical Research Council, PIP 592 (P.G.B.); Instituto Venezolano de Investigaciones Científicas - Project 898 (V.S.D.)