Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts

Abstract

Objective: To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts.Methods: Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity. Results:We found focal cortical thinning specifically in areas connected to acute infarcts (p , 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (r 5 20.39, p 5 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter.Conclusions: These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke. Remote cortical effects of acute infarcts critically contribute to functional reorganization after stroke and influence clinical outcome.1,2 We recently identified focal cortical thinning as a potential structural correlate of remote effects after ischemic lesions. In a small retrospective study on 9 patients with inherited small vessel disease, we showed that incident subcortical lacunes are associated with focal thinning in cortex connected to the infarct. 3,4 We attributed these findings to secondary cortical neurodegeneration following damage to the connecting subcortical fiber tracts. However, the study protocol and small sample size precluded a detailed assessment of these tracts and how changes in these tracts relate to changes in the connected cortex. Also, the results were obtained in a rare hereditary condition and were limited to a single infarct mechanism and to chronic, cavitating infarcts.In the current prospective, longitudinal study, we investigated the processes driving secondary neurodegeneration after acute infarcts. We measured changes of cortical thickness and microstructural integrity of connecting white matter tracts over a 6-month interval starting from stroke onset. We tested the following hypotheses: (1) cortical thinning in connected cortical regions is detectable within a few months after an acute infarct; (2) cortical thinning relates to *These authors contributed equally to this work.

Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL

“…First, in the present study, we found that CC A is independently associated with the volume of lacunes, suggesting that reduction of CC A might be secondary to degeneration of long-range fibers passing through the altered parenchyma, in line with the description of remote cortex atrophy after subcortical infarcts. 19 Note that we observed, in 10 of 26 patients, imaging aspects compatible with such secondary changes after the occurrence of lacunes in the corpus callosum fibers (Fig 3). Also, in additional analyses, we compared 28 other patients with CADASIL without lacunes from our national cohort study who were age-and sex-matched to the control group of the present study.…”

Microstructure of Strategic White Matter Tracts and Cognition in Memory Clinic Patients with Vascular Brain Injury

“…Also, using quantitative measures for hippocampal [45], gray matter, and white matter atrophy (instead of using a single quantitative measure for global atrophy as was done in the current study) might help to further increase the explained variance in cognitive functioning. Assessing regional gray matter atrophy might be particularly interesting in relation to the DTI-based assessment of strategic white matter tracts, since subcortical vascular lesions are known to cause focal cortical thinning via secondary degeneration [46]. An effort to acquire and integrate all these data into a large cohort in order to push the explained variance in cognitive functioning to a maximum would be interesting, but also very challenging.…”

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

“…A delayed apoptotic cell death occurs in the thalamus in experimental stroke models after cortical stroke that is distant to the thalamus [87], and similarly in the substantia nigra after striatal stroke that is distant from the substantia nigra [81]. After white matter stroke, connected cortical areas suffer a delayed damage that is seen as cortical thinning in magnetic resonance imaging [88], and as an overall brain atrophy [89]. In the aged brain with white matter stroke there is increased microglial activation and inflammatory cytokine release in connected cortical areas, compared with the young adult [90].…”