Clinicopathological Correlation Study on Acute Severe Stroke: Case Series

Diffuse axonal injury and demyelination are significant neuropathological features in acute severe stroke, a life-threatening condition. This study aimed to explore these changes by analyzing three middle-aged severe stroke patients with short disease duration in comparison with age-matched controls. Clinical assessments, neuropathological examinations, and whole-exome sequencing were performed. The primary lesions ranged from large ischemic infarcts to hemorrhagic lesions in strategic brain region or extensive putaminal hemorrhage. All cases exhibited brain swelling and basilar atherosclerosis, with extensive ischemic neuronal loss, particularly in the brainstem. Axonal amyloid precursor protein (APP) deposition and demyelination were observed in severe stroke cases, but these two pathologies did not overlap. Cerebral amyloid angiopathy and varied glial responses were also evident. Genetic analysis identified multiple stroke-related variants in each case, including three ischemic stroke risk variants in one case and two risk variants in two hemorrhagic cases (rs42524 of COL1A2 and rs2250889 of MMP-9 ). These findings suggest that axonal injury may occur distant from the primary lesions and that polygenic risk factors contribute to severe stroke.