Objectives: To determine the relationship between patient-reported outcome measures (PROMs) and volumetric biomarkers assessed on clinical imaging in acute ischemic stroke (AIS). Background: AIS is a leading cause of long-term disability. White matter hyperintensity (V_WMH), brain (V_Brain) and stroke lesion volume (V_Lesion) have been linked as potential determinants of functional outcomes after stroke. Recently, there has been surging attention to PROMs, which allow for direct, patient-centered health assessments of stroke victims. However, the link between neuroimaging biomarkers and PROMs is not well studied. Methods: Patients presenting to the Emergency Department at Massachusetts General Hospital between February 2017 and February 2020 with a confirmed AIS on MRI were eligible and underwent a follow-up telephone interview, including PROM-10 questionnaires. V_WMH and V_Brain were automatically determined from clinical MRI. V_Lesion was manually segmented. Regression analyses were performed to identify associations of brain volumetrics and clinical variables with PROM-10 subscores and global mental and physical summary scores. Results: Utilizing data from 150 patients (mean age: 64.7; 41.9% female), higher V_WMH was associated with worse global mental (β = -0.65), global physical (β = -0.60), social activities (OR = 0.59), physical health (OR = 0.68), fatigue (OR = 0.69) and social satisfaction (OR = 0.66) scores. V_Lesions were associated with poorer global mental (β = -0.79), social (OR = 0.55) and physical (OR = 0.66) activities, mental health (OR = 0.68) and emotional distress (OR = 0.68) scores. Higher V_Brain was linked to better global mental (β = 0.93), global physical (β = 0.79), physical activities (OR = 1.72) and mental health (OR = 1.54) scores. Conclusions: Imaging biomarkers were significantly associated with PROMs. The inclusion of these markers with PROMs in routine post-stroke assessment can enhance our understanding of recovery.

ABSTRACT Objectives To determine the relationship between patient-reported outcome measures (PROMs) and volumetric imaging markers in acute ischemic stroke (AIS). Patients and Methods Patients presenting at Massachusetts General Hospital between February 14, 2017 and February 5, 2020 with a confirmed AIS by MRI were eligible and underwent a telephone interview including PROM-10 questionnaires 3-15 months after stroke. White matter hyperintensity (V WMH ) and brain volumes (V Brain ) were automatically determined using admission clinical MRI. Stroke lesions were manually segmented and volumes calculated (V Lesion ). Multivariable and ordinal regression analyses were performed to identify associations between global and PROM-10 subscores with brain volumetrics and clinical variables. Results Utilizing data from 167 patients (mean age: 64.7; 41.9% female), higher V WMH was associated with worse global physical (β=-0.6), global mental (β=-0.65), physical health (OR=0.68), social satisfaction (OR=0.66), fatigue (OR=0.69) and social activities (OR=0.59) scores. Higher V Lesion was associated with poorer global mental (β=-0.79), mental health (OR=0.68), physical (OR=0.66) and social activities (OR=0.55), and emotional distress (OR=0.68) scores. Higher V Brain was linked to better global mental (β=0.93), global physical (β=0.79), mental health (OR=1.54) and physical activities (OR=1.72) scores. Conclusions Neuroimaging biomarkers were significantly associated with PROMs, where higher V WMH and V Lesion led to worse outcome, while higher V Brain was protective. The inclusion of neuroimaging analyses and PROMs in routine assessment provides enhanced understanding of post-stroke outcomes.

Introduction: Post-stroke cognitive impairment/dementia (PSCID) is highly prevalent and associated with poor long-term outcomes after acute ischemic stroke (AIS). Recognition of early determinants of PSCID allows for individualized interventions to reduce long-term disability. Furthermore, investigating the relation between PSCID and patient-reported outcomes provides insight into personalized impact of post-stroke cognitive dysfunction. We aimed to identify clinical determinants of PSCID and association with patient-reported outcome measures (PROMs) at 3- and 12-month after AIS. Methods: 138 AIS patients with no previous history of dementia were included. Clinical variables were acquired on hospital admission. Patients underwent a telephone interview at 3- and 12-months post-stroke including the Telephone Interview for Cognitive Status (TICS), modified Rankin scale (mRS), Barthel Index (BI) and PROM-10 questionnaires. PSCID was defined as TICS < 36 at 12-month post-stroke. Linear regression analyses were performed to identify predictors of 12-month TICS score and association with 3- and 12-month PROMs. Results: At 12 months post-stroke, 113 participants (82%) had PSCID. AIS patients with PSCID had higher rates of mRS ≥ 2 at 3-months (61.8% vs. 32%, p = 0.01), worse BI at 12-months (93.12 vs. 102, p < 0.01) and lower 12-month PROMs T Mental scores (48.22 vs. 52.41, p < 0.05). In linear regression analysis, worse functional and patient-reported outcomes at 3- and 12-months were independently associated with lower 12-month TICS (Table) . Conclusions: Large proportion of AIS patients experience PSCID at 12-months after stroke. 3-month PROMs, especially in the physical domain, are independently associated with worse cognitive measures at 12-months post-stroke. Moreover, PROMs at 12-months after AIS are strongly associated with PSCID. Incorporating PROMs in the ambulatory setting may offer additional insight into cognitive impairment after stroke.

Background and ObjectivesWhile chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological “brain age.” We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors and worse functional outcomes.MethodsWe extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison with chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs and a logistic regression model of favorable functional outcomes taking RBA as input.ResultsWe reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age = 62.8 years, 42.0% female patients). T2-FLAIR radiomics predicted chronological ages (mean absolute error = 6.9 years, r = 0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted odds ratios: 0.58, 0.76, 0.48, 0.55; all p-values < 0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes.DiscussionT2-FLAIR radiomics can be used to predict brain age and derive RBA. Older-appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke.

Background and ObjectivesAccumulating evidence suggests that gray matter atrophy, often considered a marker of Alzheimer disease (AD), can also result from cerebral small vessel disease (CSVD). Cerebral amyloid angiopathy (CAA) is a form of sporadic CSVD, diagnosed through neuroimaging criteria, that often co-occurs with AD pathology and leads to cognitive impairment. We sought to identify the role of hippocampal integrity in the development of cognitive impairment in a cohort of patients with possible and probable CAA.MethodsPatients were recruited from an ongoing CAA study at Massachusetts General Hospital. Composite scores defined performance in the cognitive domains of memory, language, executive function, and processing speed. Hippocampal subfields' volumes were measured from 3T MRI, using an automated method, and multivariate linear regression models were used to estimate their association with each cognitive domain and relationship to CAA-related neuroimaging markers.ResultsOne hundred twenty patients, 36 with possible (age mean [range]: 75.6 [65.6-88.9]), 67 with probable CAA (75.9 [59.0-94.0]), and 17 controls without cognitive impairment and CSVD (72.4 [62.5-82.7]; 76.4% female patients), were included in this study. We found a positive association between all investigated hippocampal subfields and memory and language, whereas specific subfields accounted for executive function (CA4 [Estimate = 5.43; 95% CI 1.26-9.61; p = 0.020], subiculum [Estimate = 2.85; 95% CI 0.67-5.02; p = 0.022]), and processing speed (subiculum [Estimate = 1.99; 95% CI 0.13-3.85; p = 0.036]). These findings were independent of other CAA-related markers, which did not have an influence on cognition in this cohort. Peak width of skeletonized mean diffusivity (PSMD), a measure of white matter integrity, was negatively associated with hippocampal subfields' volumes (CA3 [Estimate = -0.012; 95% CI -0.020 to -0.004; p = 0.034], CA4 [Estimate = -0.010; 95% CI -0.020 to -0.0007; p = 0.037], subiculum [Estimate = -0.019; 95% CI -0.042 to -0.0001; p = 0.003]).DiscussionThese results suggest that hippocampal integrity is an independent contributor to cognitive impairment in patients with CAA and that it might be related to loss of integrity in the white matter. Further studies exploring potential causes and directionality of the relationship between white matter and hippocampal integrity may be warranted.

To review the current evidence and ongoing clinical trials evaluating the efficacy and safety of tenecteplase (TNK), an alternative tissue plasminogen activator (tPA), in the acute management of arterial ischemic stroke (AIS). To date, alteplase is the only tPA approved by the United States FDA for use in AIS. There have been multiple phase two and three trials investigating the safety and efficacy of TNK in AIS. In patients with AIS due to large vessel occlusion, one randomized controlled trial demonstrated superiority of TNK for vessel recanalization rates and long-term functional outcomes when compared to alteplase. A meta-analysis of all phase two and three trials evaluating TNK in AIS concluded that TNK has a comparable safety and efficacy profile to alteplase. The results of these trials prompted new recommendations in the Acute Stroke Guideline published by the AHA suggesting it may be reasonable to use as an alternative to alteplase. Furthermore, recent real-world data has also reported decreased door-to-needle time with TNK utilization. In patients with AIS, use of a thrombolytic agent is standard of care and has been shown to reduce neurological disability and improve functional outcome. Randomized controlled trials have demonstrated that TNK is non-inferior to alteplase from a clinical outcome and safety standpoint. The existing data evaluating the efficacy of TNK compared to alteplase in acute AIS within 4.5 h from symptom onset showed no significant difference between these two agents with regard to functional outcome at 90 days but improved median time to treatment and large vessel recanalization in TNK-treated patients. The results from ongoing TNK trials in larger patient cohorts and in wake-up stroke populations will be instrumental to the wide-scale utilization of TNK in acute AIS management.

BACKGROUND:Ischemic stroke (IS) is a leading cause of long-term disability with sex-specific differences in outcomes. Identifying the influential factors that contribute to sex-specific disparities in stroke outcomes, therefore, holds potential to develop individualized interventions for reducing long-term disability. Further, investigating the association between sex and Patient-Reported Outcome Measures (PROMs) provides additional information on the individual impact and heterogeneity of IS. We aimed to identify sex-specific differences in stroke outcomes and relationship with PROMs in IS patients with 3-month follow-up.METHODS:Between February 2017 and February 2020, a total of 410 patients admitted with IS to the Massachusetts General Hospital, in Boston, were enrolled in this prospective cohort. At 3-month poststroke, patients were assessed for Barthel Index, modified Rankin Scale, and PROM-10 questionnaires. T scores for physical and mental health were determined from the summing of PROM-10 responses in each domain. Regression analysis was performed to identify sex-specific determinants of functional and patient-reported outcomes.RESULTS:At baseline, 242 participants were male (mean age, 65 years) and 168 were female (mean age, 70 years). Groups had similar rates of cardiovascular risk factors, admission National Institutes of Health Stroke Scale, and discharge modified Rankin Scale. At follow-up, male participants were more likely to have better rates of T Physical and Barthel Index. In regression analysis, PROMs T Physical (odds ratio, 1.06; P=0.01), Barthel Index (odds ratio, 1.06; P=0.01), and modified Rankin Scale score of ≥2 (odds ratio, 2.60; P=0.01) were associated with female sex. Female sex was also associated with lower scores for PROMs Physical subcomponents and with patient-reported general health and emotional problems.CONCLUSIONS:Women have worse outcomes after ischemic stroke, including objective measures of functional disability and patient-reported outcomes. Incorporating PROMs into IS outcome measures may offer additional insight into sex-specific differences in stroke recovery and outcomes.

Background Post-stroke cognitive impairment and dementia (PSCID) is a sequel of ischemic stroke (IS), highly prevalent and linked to poor long-term outcomes. Thus, early recognition of the clinical determinants of PSCID is urgent for identifying high-risk individuals who are susceptible to PSCID. And investigating objective measures of PSCID in relation to patient-reported outcome measures (PROMs) is essential for understanding the impact of IS. Here we identify the clinical determinants associated with PSCID and the relationship of PSCID to patient-reported outcomes in a population with IS. Methods This was a cohort study. We enrolled 138 patients who were admitted to our hospital between February 2017 and February 2020, with IS and no pre-stroke diagnosis of dementia. Clinical variables were acquired on admission. At 3 months, patients underwent a follow-up evaluation including the Telephone Interview for Cognitive Status (TICS), modified Rankin scale (mRS), Barthel Index (BI), and PROMs, using the Patient-Reported Outcomes Measurement information System Global Health (PROMIS GH). MCI/Dementia was defined as a TICS score of <36. Regression analyses were used to identify clinical, functional, and patient-reported outcome determinants of the 3-month TICS score. Analyses were adjusted for age, stroke severity, and prior IS. Results At follow-up, 113 participants (82%) were found to have MCI/Dementia. Patients with PSCID were more likely to be older, and at 3-months post-stroke they had lower rates of PROMIS GH T Mental (mean 47.69 vs. 52.13) and T Physical (mean 46.75 vs. 50.64). In multivariable linear regression analyses, increasing age ( β = −0.07, p = 0.03) and Peripheral Artery Disease (PAD; β = −3.60, p = 0.03) were independently associated with a lower TICS score. Functional and patient-reported outcomes were also associated with worse TICS, including mRS ≥ 2, BI, T Mental, Global Mental, T Physical, and Global Physical in adjusted analyses. Individual components of PROMs were also associated with TICS, including quality of life, mental health, social satisfaction, and physical activities. Conclusions In patients with IS, increased age and a pre-admission diagnosis of PAD are independently associated with worse objective measures of PSCID. Worse functional and patient-reported outcomes are also strongly linked to PSCID.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and similar to 3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich dub regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

A leading cause of white matter (WM) injury in older individuals is cerebral small vessel disease (SVD). Cerebral SVD is the most prevalent vascular contributor to cognitive impairment and dementia. Therapeutic progress for cerebral SVD and other WM disorders depends on the development and validation of neuroimaging markers suitable as outcome measures in future interventional trials. Diffusion-tensor imaging (DTI) is one of the best-suited MRI techniques for assessing the extent of WM damage in the brain. But the optimal method to analyze individual DTI data remains hindered by labor-intensive and time-consuming processes. Peak width of skeletonized mean diffusivity (PSMD), a recently developed fast, fully automated DTI marker, was designed to quantify the WM damage secondary to cerebral SVD and reflect related cognitive impairment. Despite its promising results, knowledge about PSMD is still limited in the radiologic community. This focused review provides an overview of the technical details of PSMD while synthesizing the available data on its clinical and neuroimaging associations. From a critical expert viewpoint, the authors discuss the limitations of PSMD and its current validation status as a neuroimaging marker for vascular cognitive impairment. Finally, they point out the gaps to be addressed to further advance the field.

Background and Objectives Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). Methods We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations. Discussion There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.

Background and Objectives Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). Methods We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations. Discussion There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. Trial Registration Information This study is registered under NCT04934020.

Introduction: Understanding the relations between lesions and outcomes is a particularly promising avenue to support tailored stroke care. We here employed a novel Bayesian framework integrating lesion location and functional lesion connectivity, i.e., lesion network mapping data, aiming to augment the prediction of stroke severity and the interpretability of lesion-symptom associations in a multi-center cohort of acute ischemic stroke (AIS) patients. Methods: Analyses relied on 1,077 AIS patients of the MRI-GENIE study [age: 64.2(14.7), 38%women]. NIHSS-based stroke severity was modeled via Bayesian linear regression. Structural location and functional connectivity information was represented by ten unique patterns each. We compared the out-of-sample predictive performances of structural vs. structural-functional models in Bayesian model comparisons. In ancillary analyses, we extracted functional connectivity pattern relevant for stroke severity and repeated analyses after stratifying for lesion size (50% of patients with larger lesions). Models were generally adjusted for age, sex, comorbidities and total DWI lesion volume. Results: Model comparison indicated a benefit of the combined structural-functional stroke severity prediction model compared to the structural one (model weights: 82% vs. 18%). This benefit of the combined model became even more apparent in case of patients with large lesions (97% vs. 3%). Positive lesion connectivity to the bilateral ventral attention (VA) and somatomotor networks, as well as temporal default mode network (DMN) predicted higher severity, while positive connectivity to more medial parts of the DMN and the visual network predicted lower severity. Additionally, negative lesion connectivity to the bilateral DMN, somatomotor, dorsal attention, and control networks predicted higher, and negative connectivity to the right control and bilateral VA networks predicted lower severity. Conclusions: Model comparisons indicated a benefit of integrating structural and functional information for the prediction of stroke severity, especially in case of larger lesions. Lesion connectivity data can enhance our understanding of why specific lesion locations can lead to symptoms post-stroke.

Bien que l’âge chronologique soit l'un des facteurs pronostiques les plus déterminants après un AVC ischémique, l'impact de l’âge cérébral, un biomarqueur personnalisé de santé cérébrale, reste inconnu. Nous formulons l'hypothèse que l'analyse radiomique de l'imagerie T2-FLAIR peut déterminer l’âge cérébral et qu'un âge cérébral avancé chez des patients souffrant d'un AVC ischémique est associé à plus de facteurs de risque (FdR) cardiovasculaire et à un pronostic fonctionnel péjoratif. Nous avons extraits des radiomics à partir d'images T2-FLAIR d'IRM acquises durant l’évaluation aigüe de patients victimes d'AVC. L’âge cérébral était déterminé à partir des radiomics du parenchyme cérébral à l'aide d'un régresseur ElasticNet. Puis le relative brain age (RBA), représentant l’âge cérébral d'un patient relativement aux patients d’âge chronologique similaire, était estimé. Enfin, nous avons construit un modèle de régression linéaire du RBA avec pour prédicteurs les FdR cardiovasculaire, et un modèle de régression logistique du bon pronostic fonctionnel à partir du RBA. Nous avons évalué 4163 patients issus d'une cohorte multicentrique d'AVC ischémique (âge moyen=42ans, 42%femmes). Les radiomics T2-FLAIR pouvaient prédire l’âge cérébral (erreur absolue moyenne=6,9années, r=0.81). Après ajustement, le RBA était plus élevé, et donc décrivait un cerveau d'apparence plus âgée, chez les patients présentant de l'hypertension, du diabète, un antécédent de tabagisme ou d'AVC ancien. En analyses multivariées, l’âge, le RBA, le NIHSS, ou un antécédent d'AVC étaient associés avec le pronostic fonctionnel (Odds-Ratios ajustés respectifs: 0,58; 0,76; 0,48; 0,55; p-values<0,001). De plus, l'effet péjoratif du RBA était spécialement prononcé dans les AVC peu sévères. Les radiomics T2-FLAIR peuvent prédire l’âge cérébral et déterminer le RBA. Les cerveaux d'apparence plus âgée, caractérisés par un RBA plus élevé, reflètent l'accumulation de FdR cardiovasculaires et sont associés à un pronostic fonctionnel défavorable après un AVC ischémique (figures 1 -2)

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Emerging evidence suggests that blood pressure variability (BPV) may contribute to small vessel disease (SVD) progression and cognitive impairment beyond the deleterious effects of elevated blood pressure, but the mechanisms remain largely unknown. This study investigates if BPV is associated with white matter (WM) microstructural integrity and the slope of cognitive decline in elderly individuals with cerebral amyloid angiopathy (CAA), a well characterized type of SVD. We recruited 94 non-demented individuals (73.3 ± 7.0 y, 40 F, MMSE 27.7 ± 1.5) from a memory-clinic cohort with and without possible/probable CAA with available neuropsychological evaluation and 3.0 T research MRI. Visit-to-visit BPV was assessed using the coefficient of variation derived from the serial outpatient BP measures during a 5-year interval. A novel diffusion tensor imaging marker – peak width of skeletonized mean diffusivity (PSMD) – was used to evaluate the WM integrity. Using linear regression models, we evaluated the association of PSMD with BPV, adjusted for standard cardiovascular risk factors. We found a significant association between loss of WM integrity and high systolic BPV (β = 0.37, P < 0.001), but not mean BP. The association remained significant after adjusting for age, antihypertensive medication usage, diabetes, smoking, and body mass index. Furthermore, the association of BPV with WM integrity was stronger when CAA was present ( P for interaction = 0.018). Higher BPV at baseline was associated with worse executive function in CAA patients at 2-year follow-up (β = -0.53, P = 0.003), adjusted for baseline function. Our findings show that visit-to-visit BP fluctuations are associated with loss of WM microstructural integrity and cognitive decline. The association between BP variability and WM integrity might in part be driven by CAA pathology. Further studies are warranted to disentangle the relationship between BP fluctuations, microvascular injury, and cognitive impairment in older adults.

Background The relationship of global white matter microstructural integrity and ischemic stroke outcomes is not well understood. Aims To investigate the relationship of global white matter microstructural integrity with clinical variables and functional outcomes after acute ischemic stroke. Methods A retrospective analysis of neuroimaging data from 300 acute ischemic stroke patients with magnetic resonance imaging brain obtained within 48 hours of stroke onset and long-term functional outcomes (modified Rankin, mRS) was performed. Peak width of skeletonized mean diffusivity (PSMD), as a measure of global white matter microstructural injury, was calculated in the hemisphere contralateral to the acute infarct. Multivariable linear and logistic regression analyses were performed to identify variables associated with PSMD and excellent functional outcome (mRS < 2) at 90 days, respectively. Mediation analysis was then pursued to characterize how PSMD mediates the effect of age on acute ischemic stroke functional outcomes. Results White matter hyperintensity volume, age, pre-stroke disability, and normal-appearing white matter mean diffusivity were independently associated with increased PSMD. In logistic regression analysis, increased infarct volume and PSMD were independent predictors of excellent functional outcome. Additionally, the effect of age on functional outcomes was indirectly mediated by PSMD ( P < 0.001). Conclusions As a marker of global white matter microstructural injury, increased PSMD mediates the effect of increased age to contribute to poor acute ischemic stroke functional outcomes. PSMD could serve as a putative radiographic marker of brain age for stroke outcomes prognostication.

Introduction For patients with large vessel occlusion (LVO) stroke, time to treatment with endovascular thrombectomy (EVT) is crucial to prevent infarction and improve outcomes. We sought to evaluate the arrival-to-puncture times and outcomes for transferred patients accepted directly to the angio-suite (LVO2OR) versus those accepted through the emergency department (ED) in a hub-and-spoke telestroke network. Methods Consecutive patients transferred for EVT with spoke CTA-confirmed LVO, spoke ASPECTS >6, and LKW-to-hub arrival <6 hours were identified. Our LVO2OR protocol began implementation in January 2017. The LVO2OR cohort includes patients who underwent EVT from July 2017 to October 2020; the ED cohort includes those from January 2011 to December 2016. Arrival-to-puncture time and 90-day modified Rankin Scale (mRS) were prospectively recorded. Results The LVO2OR cohort was comprised of 91 patients and the ED cohort 90. LVO2OR patients had more atrial fibrillation (AF, 51% vs 32%, p=0.02) and more M2 occlusions (27% vs 10%, p=0.01). LVO2OR patients had faster median hub arrival-to-puncture time (11 vs 92 minutes, p<0.001), faster median telestroke consult-to-puncture time (2.4 vs 3.6 hours, p<0.001), greater TICI 2b-3 reperfusion (92% vs 69%, p<0.001), and greater 90-day mRS <2 (35% vs 21%, p=0.04). In a multivariable model, LVO2OR significantly increased the odds of 90-day mRS <2 (aOR 2.77, 95%CI 1.07,7.20; p=0.04) even when controlling for age, baseline mRS, AF, NIHSS, M2 location, and TICI 2b-3. Conclusion In a hub-and-spoke telestroke network, accepting transferred patients directly to the angio-suite was associated with dramatically reduced arrival-to-puncture time and may lead to improved 90-day outcomes. Direct-to-angio-suite protocols should continue to be evaluated in other regions and telestroke models. Disclosures R. Regenhardt: None. J. Rosenthal: None. A. Dmytriw: None. J. Vranic: None. A. Bonkhoff: None. M. Bretzner: None. J. Hirsch: None. J. Rabinov: None. C. Stapleton: None. A. Patel: None. A. Singhal: None. N. Rost: None. T. Leslie-mazwi: None. M. Etherton: None.

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.