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

Abstract

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.

SynthSR: A public AI tool to turn heterogeneous clinical brain scans into high-resolution T1-weighted images for 3D morphometry

“…Morphometry of brain MRI of patients with stroke is important in the discovery of imaging biomarkers of outcome ( 66 ) and to study post-stroke dementia, which is becoming increasingly common as stroke mortality rates decrease ( 67 ). Unfortunately, there are (to the best of our knowledge) no morphometric tools that can readily cope with the abnormal distributions of shape and image intensity distribution caused by stroke, which forces studies to discard many cases that do not pass quality control ( 68 )—not only decreasing sample sizes but also introducing a potential selection bias.…”

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke

“…This is critical because recent work suggests that cross-sectional brain age may reflect either early-life differences or volume loss due to isolated incidents, such as stroke. 45 Furthermore, as previously noted, 24,25 although our large heterogeneous dataset provides statistical power and diverse data to test hypotheses, there are limited covariates that are present across the entire dataset. Additional factors known to influence brain age-such as genetics, neurodegenerative copathology such as microvascular damage, lifestyle factors, and comorbidities-should be examined in future studies.…”

Global brain health modulates the impact of lesion damage on post-stroke sensorimotor outcomes

“…Cellular and genetic measures, across the acute to chronic stages, may help to tease apart which mechanisms lead brains to be more vulnerable and less resilient to insult. In addition, as noted previously, 24,25 although our large, multi-site retrospective dataset provides excellent statistical power and diverse data to test hypotheses, there are limitations as to which covariates were present across the entire dataset. Additional factors known to influence brain age -such as race/ancestry, education, neurodegenerative copathology, and co-morbidities such as diabetes mellitus, hypercholesterolemia, and atrial fibrillation -should be examined in future studies.…”

“…Second, we expected that higher brain-PAD would be associated with worse sensorimotor outcomes, as well as worse global outcomes across multiple functional domains, due to less residual brain tissue available to support neuroplastic changes required for recovery. Assuming that brain-PAD partly reflects post-stroke secondary atrophy, we further hypothesized that the association between brain-PAD and sensorimotor behavior should be strongest in the ipsilesional hemisphere, which should undergo more changes with functional relevance compared to the contralesional hemisphere, [24][25][26] and in the chronic stage after stroke, allowing ample time for post-stroke atrophy to occur.…”