Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke

We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.FSW – Publicaties zonder aanstelling Universiteit Leide

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis

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.Artemis Zavaliangos-Petropulu, PhD, Bethany Lo, BSc, Miranda R. Donnelly, MS, Nicolas Schweighofer, PhD, Keith Lohse, PhD, PStat, Neda Jahanshad, PhD, Giuseppe Barisano, MD, Nerisa Banaj, PhD, Michael R. Borich, PhD, Lara A. Boyd, PhD, Cathrin M. Buetefisch, MD, PhD, Winston D. Byblow, PhD, Jessica M. Cassidy, PhD, Charalambos C. Charalambous, PhD, Adriana B. Conforto, PhD, Julie A. DiCarlo, MSc, Adrienne N. Dula, PhD, Natalia Egorova-Brumley, PhD, Mark R. Etherton, MD, PhD, Wuwei Feng, MD, Kelene A. Fercho, PhD, Fatemeh Geranmayeh, PhD, Colleen A. Hanlon, PhD, Kathryn S. Hayward, PhD, Brenton Hordacre, PhD, Steven A. Kautz, PhD, Mohamed Salah Khlif, PhD, Hosung Kim, PhD, Amy Kuceyeski, PhD, David J. Lin, MD, Jingchun Liu, MD, Martin Lotze, MD, Bradley J. MacIntosh, PhD, John L. Margetis, OTD, Feroze B. Mohamed, PhD, Fabrizio Piras, PhD, Ander Ramos-Murguialday, PhD, Kate P. Revill, PhD, Pamela S. Roberts, PhD, Andrew D. Robertson, PhD, Heidi M. Schambra, MD, Na Jin Seo, PhD, Mark S. Shiroishi, MD, Cathy M. Stinear, PhD, Surjo R. Soekadar, MD, Gianfranco Spalletta, MD, PhD, Myriam Taga, PhD, Wai Kwong Tang, MD, Gregory T. Thielman, EdD, Daniela Vecchio, PhD, Nick S. Ward, MD, Lars T. Westlye, PhD, Emilio Werden, PhD, Carolee Winstein, PhD, PT, George F. Wittenberg, MD, PhD, Steven L. Wolf, PhD, Kristin A. Wong, MD, Chunshui Yu, MD, Amy Brodtmann, MD, PhD, Steven C. Cramer, MD, Paul M. Thompson, PhD, Sook-Lei Liew, PhD, OTR,