Cerebral Infarction

IntroductionMyelin is pivotal for signal transfer and thus cognition. Cerebral small vessel disease (cSVD) is primarily associated with white matter (WM) lesions and diffusion changes; however, myelin alterations and related cognitive impairments in cSVD remain unclear.MethodsWe included 64 patients with familial cSVD (i.e., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]) and 20 cognitively unimpaired individuals. χ separation applied to susceptibility weighted imaging was used to assess myelin and iron within WM hyperintensities, normal appearing WM, and two strategic fiber tracts. Diffusion-based mean diffusivity and free water were analyzed for comparisons. Cognitive impairment was assessed by the Trail Making Test.ResultsCADASIL patients showed reduced myelin within WM hyperintensities and its penumbra in the normal appearing WM. Myelin was moderately correlated with diffusion and iron changes and associated with slower processing speed controlled for diffusion and iron alterations.DiscussionMyelin constitutes WM alterations distinct from diffusion changes and substantially contributes to explaining cognitive impairment in cSVD.Highlightsχ-negative magnetic resonance signal was reduced within white matter hyperintensities and normal appearing white matter in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting widespread myelin decreases due to cerebral small vessel disease (cSVD). χ-negative values were only moderately associated with diffusion tensor imaging derived indices including free water and mean diffusivity, suggesting that χ separation depicts distinct microstructural changes in cSVD. Alterations in χ-negative values made a unique contribution to explain processing speed impairment, even when controlled for diffusion and iron changes.

AimsIschemic stroke is increasingly treated by mechanical thrombectomy (MT) with the more rapid and complete reperfusion of the ischemic tissue, enhancing patient outcome, compared to recombinant tissue plasminogen activator (rtPA) alone. Even so, there is still extensive brain infarction and disability following MT, which is exacerbated by ischemia-reperfusion injury (IRI) and other pathological processes during reperfusion. Hence, an adjunct therapy to MT that decreases IRI should enhance patient outcomes.Methods and resultsTo test this possibility, we adapted the transient middle cerebral artery occlusion (tMCAO) mouse model to allow local intra-arterial administration of acidified disodium malonate (aDSM) to decrease IRI as the ischemic tissue was reperfused. Administration of aDSM (160 mg/kg; pH 6) during reperfusion decreased brain infarct volume by ∼60% when assessed by magnetic resonance imaging (MRI) 24 h after reperfusion and improved neurological function.ConclusionThese findings suggest aDSM as a potential adjunct therapy to further improve outcomes for stroke patients treated by MT.

Cortical cerebral microinfarcts are associated with brain atrophy in cross-sectional studies, with further investigation using longitudinal datasets being warranted. Moreover, little is known about their combined impact on cognition. This study aimed to establish the association between cortical cerebral microinfarcts and brain volume loss over time and explore whether they synergistically contribute to cognitive decline. A total of 475 patients, aged 72.7 ± 7.9 years, were enrolled from a memory clinic cohort, who underwent neuroimaging and neuropsychological assessments at least twice over 5 years. Cortical cerebral microinfarcts and other cerebrovascular disease were assessed using 3-T MRI. Brain volumes were calculated semi-automatically using FreeSurfer. Cognitive function was assessed using a neuropsychological test battery including six domains. Linear mixed-effect models were utilized to examine the association between cortical cerebral microinfarcts and brain volume loss and their interaction on cognitive decline. Estimated marginal means were derived to plot global cognitive trajectories. Cortical cerebral microinfarcts were associated with a greater decrease over 2 years in total brain volume [β = -1.94 (-3.07, -0.82) at Year 2, P-interaction with time < 0.001], grey matter volume [β = -1.00 (-1.69, -0.30) at Year 2, P-interaction = 0.002] and white matter volume [β = -0.95 (-1.54, -0.35) at Year 2, P-interaction < 0.001]. Brain volume loss was more pronounced in patients with multiple microinfarcts. Patients with high brain volume loss and cortical cerebral microinfarcts, particularly multiple microinfarcts, exhibited significantly lower global cognitive scores [single microinfarct: β = -1.83 (-2.68, -0.97) at Year 5, P-interaction with time < 0.001; multiple microinfarcts: β = -3.13 (-4.21, -2.05) at Year 5, P-interaction < 0.001]. The synergistic effects were more significant in the domains of executive function, memory, language and visuospatial function. Global cognitive trajectories revealed greater cognitive decline in patients with high brain volume loss and single or multiple microinfarcts, with the latter showing the steepest slope. This study established a longitudinal association between cortical cerebral microinfarcts and brain atrophy progression, with higher microinfarct burden associated with more pronounced brain volume loss. Furthermore, cortical cerebral microinfarcts and brain atrophy showed synergistic effects on cognitive decline. These findings highlight the importance of investigating the role of mixed pathologies in the development of cognitive impairment and dementia in future research.

Cerebral small vessel diseases (cSVDs) contribute significantly to stroke and dementia. Advanced 7 T MRI techniques have revealed small vessel dysfunction in cSVD patients, linked to global white matter damage cross-sectionally. However, it remains unclear whether these vascular deficits predict progressive tissue damage. This longitudinal study examined the spatial relationship between local vascular function and white matter damage progression in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Twenty-two patients underwent baseline small vessel function assessment using 7 T MRI. Voxelwise blood-oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) to a hypercapnic was evaluated. White matter changes were assessed on 3 T MRI over two years, analyzing mean diffusivity changes and conversion of normal-appearing white matter to white matter hyperintensities (WMH). Results showed significant global increases in white matter damage over time. Voxelwise analysis revealed that lower baseline BOLD-CVR magnitude and higher dispersion were associated with increased white matter damage and WMH progression at specific locations at follow-up. However, whole-brain vascular function measures did not predict white matter changes at a global level. These findings suggest that local vascular function plays a key role in white matter damage progression in CADASIL, highlighting the importance of regional vascular health in cSVDs.