ABSTRACT BACKGROUND Perivascular Spaces (PVS) are a marker of cerebral small vessel disease (CSVD) that are visible on brain imaging. Larger PVS has been associated with poor quality of life and cognitive impairment post-stroke. However, the association between PVS and post-stroke sensorimotor outcomes has not been investigated. METHODS 602 individuals with a history of stroke across 24 research cohorts from the ENIGMA Stroke Recovery Working Group were included. PVS volume fractions were obtained using a validated, automated segmentation pipeline from the basal ganglia (BG) and white matter centrum semiovale (CSO), separately. Robust mixed effects regressions were used to a) examine the cross-sectional association between PVS volume fraction and post-stroke sensorimotor outcomes and b) to examine whether PVS volume fraction was associated with other measures of CSVD and overall brain health (e.g., white matter hyperintensities [WMHs], brain age [measured by predicted age difference, brain-PAD]). RESULTS Larger PVS volume fraction in the CSO, but not BG, was associated with worse post-stroke sensorimotor outcomes (b = -0.06, p = 0.047). Higher burden of deep WMH (b = 0.25, p <0.001), periventricular WMH (b = 0.16, p <0.001) and higher brain-PAD (b = 0.09, p <0.001) were associated with larger PVS volume fraction in the CSO. CONCLUSIONS Our data show that PVS volume fraction in the CSO is cross-sectionally associated with sensorimotor outcomes after stroke, above and beyond standard lesion metrics. PVS may provide insight into how the overall vascular health of the brain impacts inter-individual differences in post-stroke sensorimotor outcomes.
Evaluate the association of remotely captured ambulatory activity with structural central nervous system pathology via quantitative magnetic imaging, in people with multiple sclerosis (MS).
Background:
Remote activity monitoring has the potential to evaluate real-world motor function and disability outside of the clinic. The relationships of daily physical activity with spinal cord white matter and grey matter areas, MS disability, and leg function are unknown.
Design/Methods:
Fifty adults with progressive or relapsing MS with motor disability who could walk at least 2 minutes, were assessed using clinical, patient-reported, and quantitative brain and spinal cord MRI measures. Fitbit Flex2, worn on the non-dominant wrist, remotely assessed activity over 30 consecutive days. Univariate and multivariate analyses were performed to assess correlations between remote physical activity and other disability metrics.
Results:
The mean age of the cohort was 53.3 years and the median EDSS was 4.0. Average daily step counts (STEPS) were highly correlated with EDSS and walking measures (i.e., Timed 25-foot Walk, Timed up and Go tests, and subjective 12-item MS Walking Scale). Greater STEPS correlated with greater C2-C3 spinal cord grey matter areas (rho=0.39, p=0.04), total cord area (rho=0.35, p=0.04), and brain volume (rho=0.32, p=0.04).
Conclusions:
These results provide preliminary evidence that spinal cord grey matter area is a neuroanatomical substrate associated with STEPS. STEPS could serve as a proxy to alert clinicians and researchers to possible changes in structural nervous system pathology. Disclosure: Dr. Block has nothing to disclose. Shuiting Cheng has nothing to disclose. An immediate family member of Jeremy Juwono has received personal compensation for serving as an employee of Metropolitan Transportation Commission . Jeremy Juwono has received personal compensation for serving as an employee of UCSF. Dr. Cuneo has nothing to disclose. Gina Kirkish has nothing to disclose. Amber M. Alexander has nothing to disclose. Dr. Khan has nothing to disclose. Mr. Science has nothing to disclose. Dr. Caverzasi has nothing to disclose. The institution of Nico Papinutto has received research support from National Center for Advancing Translational Sciences, National Institutes of Health, through a UCSF-CTSI Grant . The institution of Nico Papinutto has received research support from Race to Erase MS Foundation. William Stern has nothing to disclose. Refujia Gomez has nothing to disclose. Mark Pletcher has nothing to disclose. Gregory Marcus has received stock or an ownership interest from InCarda . The institution of Gregory Marcus has received research support from Jawbone . Jeffrey Olgin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson and Johnson. The institution of Jeffrey Olgin has received research support from Samsung. The institution of Jeffrey Olgin has received research support from NIH. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant and Expert, Vaccine Injury Compensation Program with United States Health and Human Services and Department of Justice. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Therini. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. Dr. Cree has received publishing royalties from a publication relating to health care. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDDAY. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi/Genzyme.
Abstract Regional neuron loss following stroke can result in remote brain changes due to diaschisis and secondary brain atrophy. Whole brain changes post-stroke can be captured by the predicted brain age difference (brain-PAD), a neuroimaging-derived biomarker of global brain health previously associated with poorer chronic stroke outcomes. We hypothesized that greater lesion damage would be longitudinally associated with worsening brain-PAD during subacute stroke, and conversely, that poorer baseline brain-PAD would be associated with enlarged lesion damage. We prospectively collected MRIs from 47 stroke patients across three sites within 3 weeks (baseline) and at 3 months (follow-up) post-stroke. Predicted brain age was estimated via a pretrained ridge regression model using 77 morphological features. Brain-PAD was calculated as predicted age minus chronological age. Robust linear mixed effects regression models were used to examine relationships between infarct volume and brain-PAD, adjusting for age, sex, time, and intracranial volume at baseline. Larger baseline infarct volume was associated with accelerated brain aging at 3 months (β=0.87, p=0.023). Conversely, larger baseline brain-PAD predicted larger increase in infarct volume at 3 months (β=0.02, p=0.009). These findings reveal a bidirectional relationship between focal stroke damage and global brain health during the subacute period, underscoring the importance of assessing both.
Background: Remote activity monitoring has the potential to evaluate real-world, motor function, and disability at home. The relationships of daily physical activity with spinal cord white matter and gray matter (GM) areas, multiple sclerosis (MS) disability and leg function, are unknown. Objective: Evaluate the association of structural central nervous system pathology with ambulatory disability. Methods: Fifty adults with progressive or relapsing MS with motor disability who could walk >2 minutes were assessed using clinician-evaluated, patient-reported outcomes, and quantitative brain and spinal cord magnetic resonance imaging (MRI) measures. Fitbit Flex2, worn on the non-dominant wrist, remotely assessed activity over 30 days. Univariate and multivariate analyses were performed to assess correlations between physical activity and other disability metrics. Results: Mean age was 53.3 years and median Expanded Disability Status Scale (EDSS) was 4.0. Average daily step counts (STEPS) were highly correlated with EDSS and walking measures. Greater STEPS were significantly correlated with greater C2-C3 spinal cord GM areas (ρ = 0.39, p = 0.04), total cord area (TCA; ρ = 0.35, p = 0.04), and cortical GM volume (ρ = 0.32, p = 0.04). Conclusion These results provide preliminary evidence that spinal cord GM area is a neuroanatomical substrate associated with STEPS. STEPS could serve as a proxy to alert clinicians and researchers to possible changes in structural nervous system pathology.
Abstract BACKGROUND Brain age, a proxy of overall brain health estimated from structural neuroimaging, has been associated with sensorimotor performance in chronic stroke. Similarly, post-stroke cognitive outcomes have been associated with accelerated brain aging. However, the relationships between brain age, sensorimotor, and cognitive outcomes in early subacute stroke (<3 months after onset) are less understood. METHODS In this work, we investigated associations between stroke survivors’ brain-predicted age difference (brain-PAD, quantified as a person’s brain age minus their chronological age) and longitudinal measurements of motor impairment (Fugl-Meyer Upper Extremity Assessment [FMUE]) and cognitive impairment (Montreal Cognitive Assessment [MoCA]) in subacute stroke. We used high-resolution T1-weighted MRIs from 44 participants at baseline and three months after stroke onset to investigate associations between brain-PAD, MoCA, and FMUE scores with robust linear mixed-effects regression models and mediation analyses. RESULTS We found negative associations between baseline brain-PAD and FMUE at baseline (β=-0.87, p=0.029) and three months (β=-0.87, p=0.011). Baseline brain-PAD was also negatively correlated with MoCA at three months (β=-0.13, p=0.015) but not at baseline (β=-0.11, p=0.141). Baseline brain-PAD was not associated with changes in FMUE (β=-0.01, p=0.930) or MoCA (β=-0.03, p=0.579). Finally, MoCA was not associated with FMUE at either time point, nor did it mediate the relationship between brain-PAD and FMUE. CONCLUSION Overall, we show that baseline brain age predicts both motor and cognitive outcomes at three months. However, motor and cognitive outcomes are not directly associated with one other. This suggests that brain age is representative of changes in multiple, distinct neurological pathways post-stroke. Further research with longer time intervals is needed to examine whether brain age also predicts chronic stroke outcomes.
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