The contribution of white matter pathology, hypoperfusion, lesion load, and stroke recurrence to language deficits following acute subcortical left hemisphere stroke

Abstract

Aphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute ischemic left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. We found that language performance was negatively correlated with acute/total lesion volumes and greater damage to substructures of the deep white matter and basal ganglia. We conducted a LASSO regression that included all variables for which we found significant univariate relationships to language performance, plus nuisance regressors. Only total lesion volume was a significant predictor of global language impairment severity. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals.

Association of Circumscribed Subcortical Gray and White Matter Lesions With Apraxic Deficits in Patients With Left Hemisphere Stroke

“…Furthermore, other studies did not find a consistent association between cortical hypoperfusion and aphasia after acute subcortical LH stroke. 42,43 In this study, we identified the caudate nucleus as the only subcortical structure whose amount of damage (independent of total lesion size) was associated with apraxia.…”

“…Furthermore, other studies did not find a consistent association between cortical hypoperfusion and aphasia after acute subcortical LH stroke. 42,43…”

Discourse- and lesion-based aphasia quotient estimation using machine learning

“…EC tracts are also adjacent to portions of SLF ( Schmahmann et al, 2009 ), raising the possibility that these two pathways are commonly damaged together in stroke affecting the middle cerebral artery. It is also possible that the EC contributes to language via subcortical connections that support language either directly or through domain-general processes ( Kuljic-Obradovic, 2003 , Sharif et al, 2022 ). The MOG, on the other hand, may be related to visual identification of items and objects near the ‘beginning’ of the ventral language stream ( Fridriksson et al, 2016 , Hickok and Poeppel, 2004 , Hickok and Poeppel, 2016 ).…”

Understanding recovery of language after stroke: insights from neurovascular MRI studies

“…Interestingly, a recent study showed that cortical hypoperfusion in the left hemisphere was more likely a determining factor of language deficits in subcortical aphasia rather than direct effect of the lesion in the basal ganglia ( n = 19) ( Celebi et al, 2022 ), replicating an effect observed earlier in acute subcortical aphasia ( Hillis et al, 2002 ). However, another study did not find cortical hypoperfusion to be a contributing factor to the severity of acute subcortical aphasia ( Sharif et al, 2022 ). The discrepancies in the results are likely due to varying methods used to assess cortical perfusion, with the latter study with null effects relying on hyperintense vessels on FLAIR scans to estimate regions of decreased blood flow.…”