Dynamic Regional Brain Atrophy Rates in the First Year After Ischemic Stroke

Abstract

Background and Purpose: Brain atrophy can be regarded as an end-organ effect of cumulative cardiovascular risk factors. Accelerated brain atrophy is described following ischemic stroke, but it is not known whether atrophy rates vary over the poststroke period. Examining rates of brain atrophy allows the identification of potential therapeutic windows for interventions to prevent poststroke brain atrophy. Methods: We charted total and regional brain volume and cortical thickness trajectories, comparing atrophy rates over 2 time periods in the first year after ischemic stroke: within 3 months (early period) and between 3 and 12 months (later period). Patients with first-ever or recurrent ischemic stroke were recruited from 3 Melbourne hospitals at 1 of 2 poststroke time points: within 6 weeks (baseline) or 3 months. Whole-brain 3T magnetic resonance imaging was performed at 3 time points: baseline, 3 months, and 12 months. Eighty-six stroke participants completed testing at baseline; 125 at 3 months (76 baseline follow-up plus 49 delayed recruitment); and 113 participants at 12 months. Their data were compared with 40 healthy control participants with identical testing. We examined 5 brain measures: hippocampal volume, thalamic volume, total brain and hemispheric brain volume, and cortical thickness. We tested whether brain atrophy rates differed between time points and groups. A linear mixed-effect model was used to compare brain structural changes, including age, sex, years of education, a composite cerebrovascular risk factor score, and total intracranial volume as covariates. Results: Atrophy rates were greater in stroke than control participants. Ipsilesional hemispheric, hippocampal, and thalamic atrophy rates were 2 to 4 times greater in the early versus later period. Conclusions: Regional atrophy rates vary over the first year after stroke. Rapid brain volume loss in the first 3 months after stroke may represent a potential window for intervention. REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02205424.

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

“…Our results support the hypothesis that non-lesioned deep gray structures serve distinct roles in subacute versus chronic stroke, which is not surprising given the cascade of neurobiological and neuroinflammatory processes that occur early after stroke (Murphy and Corbett, 2009; Ward, 2017). Within 90 days after stroke, only the ipsilesional thalamus showed detectable associations with post-stroke sensorimotor behavior, in line with recent research suggesting a role for the thalamus in subacute recovery (Brodtmann et al ., 2020). A smaller thalamic volume could reflect cell loss and thalamic dysfunction, thereby limiting resources critical for early recovery (Fries et al ., 1993; Brodtmann et al ., 2020).…”

“…These findings suggest that, post-stroke, subcortical brain alterations related to sensorimotor behavior occur most prominently in the hemisphere directly affected by the stroke. This was observed despite the fact that, after stroke, atrophy and reorganization has been observed bilaterally (Brodtmann et al ., 2020). The identification of sensorimotor relationships with specific ipsilesional subcortical nuclei may provide novel neuromodulatory or pharmacological targets to improve stroke outcomes.…”

“…23, 24 Within 90 days after stroke, only the ipsilesional thalamus showed detectable associations with post-stroke sensorimotor behavior, in line with recent research showing marked thalamic atrophy, particularly within the first three months post-stroke. 8 A smaller thalamic volume could reflect cell loss and thalamic dysfunction, thereby limiting resources critical for early recovery. 5, 8 Importantly, in our data, this relationship persists, and is stronger, when looking at only the first 21 days post-stroke.…”

“…8 A smaller thalamic volume could reflect cell loss and thalamic dysfunction, thereby limiting resources critical for early recovery. 5, 8 Importantly, in our data, this relationship persists, and is stronger, when looking at only the first 21 days post-stroke. As non-lesioned brain volumes within six weeks after stroke are assumed to be similar to those before the stroke, 25 this finding suggests that larger thalamic volumes prior to stroke could provide a neuroprotective effect.…”

“…Research has shown that lesions to the thalamus and basal ganglia result in poor stroke outcomes, given their roles in sensorimotor control along with learning, motivation, reward, and cognition. 3–7 Atrophy of these structures has been reported after stroke 8 and related to cognitive deficits. 9 However, little is known about whether and how atrophy to spared subcortical regions relates to subsequent sensorimotor behavior.…”