Topographic Localization of Chronic Cerebellar Ischemic Lesions: Implications for Underlying Cause

BACKGROUND: Chronic cerebellar lesions of presumed ischemic origin are frequently found in patients with ischemic stroke and as incidental findings. However, the differentiation of embolic lesions from lesions caused by cerebral small vessel disease (SVD) is unclear. We aimed to investigate whether the location of chronic cerebellar ischemic lesions (deep versus cortical) indicates the underlying cause (embolic versus SVD). METHODS: This study was a post hoc data analysis from the multinational ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Patients With Postischemic Stroke With Atrial Fibrillation), which included patients with acute ischemic stroke and atrial fibrillation cohort between 2017 and 2022. For comparison, data from 2 cohorts (DiViNAS [Disease Variability in NOTCH3-Associated SVD] and VASCAMY [Vascular and Amyloid Predictors of Neurodegeneration and Cognitive Decline in Nondemented Subjects]) consisting of participants with hereditary cerebral SVD (ie, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) were analyzed (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cohort). Brain magnetic resonance imaging scans were evaluated for presence and location of chronic cerebellar ischemic lesions. The association between these lesions and the severity of supratentorial SVD was analyzed using univariable and multivariable models, adjusting for key covariables. RESULTS: In the atrial fibrillation cohort (N=790), 278 (35%) patients had chronic cerebellar ischemic lesions (cortical: n=242; deep: n=36). In multivariable analyses, features of cerebral SVD were associated with deep cerebellar ischemic lesions (summary SVD score; odds ratio per point, 2.5 [95% CI, 1.5–3.5]; P <0.001), while there was no association of SVD markers and cortical cerebellar ischemic lesions (summary SVD score; odds ratio per point, 1.1 [95% CI, 0.9–1.3]; P =0.107). In the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cohort (N=257), chronic cerebellar ischemic lesions (n=108 [42%]) were almost exclusively identified in deep cerebellar regions (n=101, 94%). CONCLUSIONS: Chronic cerebellar ischemic lesions in deep but not cortical regions were associated with supratentorial cerebral SVD. Therefore, cerebral SVD is likely the primary cause of chronic ischemic lesions in deep cerebellar regions, while cortical cerebellar lesions are more likely attributable to embolic etiologies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03148457.