Lin Kooi Ong, PhD
Brodtmann A, Khlif MS, Egorova N, Veldsman M, Bird LJ, Werden E. Dynamic Regional Brain Atrophy Rates in the First Year After Ischemic Stroke. Stroke. 2020;51:e183–e192.
Brain atrophy refers to a loss of brain cells or a loss in the networks between brain cells, and is a common feature for many neurodegenerative diseases. Ischemic stroke is usually viewed as an acute cerebrovascular injury, and not as a neurodegenerative condition. Nevertheless, there is now emerging evidence demonstrating that stroke can cause persistent regional brain atrophy for months and even years after the initial event. Further, this regional brain atrophy after stroke has been linked to several late phase functional disturbances, including cognitive impairment. Notably, stroke increases the risk of developing vascular dementia.
The CANVAS study (Cognition and Neocortical Volume After Stroke) is a longitudinal study in people recruited from Melbourne hospitals, Australia, following ischemic stroke, comparing brain volume and cognitive function over 3 years with a group of healthy age- and sex-matched control participants.(1) In this article, Brodtmann and colleagues examined the trajectories of total and regional brain volume changes in the first year following stroke. Specifically, brain magnetic resonance imaging (MRI) was performed on stroke and healthy control participants, with 86 stroke participants completing testing at baseline, 125 at 3 months, and 113 participants at 12 months, as well as 40 healthy control participants. Five brain measures — hippocampal volume, thalamic volume, total brain and hemispheric brain volume, and cortical thickness — were examined to evaluate whether brain atrophy rates differed between time points and groups.
This study demonstrated that brain atrophy rates were greater in stroke participants compared to healthy controls. Furthermore, ipsilesional hemispheric, hippocampal, and thalamic atrophy rates were greater from baseline to 3 months (early period) versus from 3 to 12 months (later period). Remarkably, the rate of ipsilesional thalamic atrophy in the early period was the most prominent at 2.14 mm3/day, and approximately 4.5 times faster than the later period at 0.48 mm3/day. The rate of ipsilesional hippocampal atrophy was much greater in the early period (0.64 mm3/day) compared to later (0.08 mm3/day).
These findings provide further neuroimaging evidence that brain damage is not only confined to the primary infarction after ischemic stroke, but also in remote regions of the brain at different degree. Degeneration of remote brain regions that are connected to the primary infarction or “secondary neurodegeneration” has been consistently observed in the thalamus, substantia nigra and pyramidal tract after cerebral infarction in the middle cerebral artery territory.(2) However, only limited studies have investigated hippocampal atrophy after ischemic stroke.(3,4) While the mechanisms involved in the development of regional brain atrophy have not been fully elucidated, studies in rodent stroke models have shed some light, suggesting that Wallerian degeneration and neuroinflammation are most likely involved. However, the involvement of neurotoxic proteins, such as amyloid-β, remains ambiguous.(5) It would be of interest to cover the potential mechanisms of secondary neurodegeneration in detail, but that is for another blog post. Therapeutic strategies to target secondary neurodegeneration processes may be promising approaches to prevent or delay post-stroke cognitive impairment.
1. Brodtmann A, Werden E, Pardoe H, et al. Charting cognitive and volumetric trajectories after stroke: protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study. Int J Stroke. 2014;9:824–828.
2. Zhang J, Zhang Y, Xing S, et al. Secondary neurodegeneration in remote regions after focal cerebral infarction: a new target for stroke management? Stroke. 2012;43:1700-1705.
3. Gemmell E, Bosomworth H, Allan L, et al. Hippocampal neuronal atrophy and cognitive function in delayed poststroke and aging-related dementias. Stroke. 2012;43:808-814.
4. Haque ME, Gabr RE, Hasan KM, et al. Ongoing secondary degeneration of the limbic system in patients with ischemic stroke: a longitudinal MRI Study. Front Neurol. 2019;10:154.
5. Ong LK, Walker FR and Nilsson M. Is Stroke a Neurodegenerative Condition? A Critical Review of Secondary Neurodegeneration and Amyloid-beta Accumulation after Stroke. AIMS Medical Science. 2017;4:1-16.