Evaluating the Role of Perilesional Tissue in Pathobiology of Epileptogenesis of Vascular Malformations of the Central Nervous System

BACKGROUND AND PURPOSE: Seizures are common presentation of cerebral vascular malformation (CVM). Topography and haemodynamic alterations are proposed as mechanisms for epileptogenesis, but the role of glial/neuronal alterations in perilesional tissue has not received much attention. Identification of the exact pathophysiologic basis could have therapeutic implications. To evaluate whether angioarchitectural factors of CVM or alterations in neuroglial/stroma of the adjacent cortex contribute to seizures. METHOD: The clinical, imaging and histological characteristics of arteriovenous malformation (AVM) and cerebral cavernous malformation (CCM) with and without seizures was evaluated using neuroimaging imaging and digital subtraction angiography parameters and histopathology by morphology and immunohistochemistry. RESULTS: Fifty-six cases of CVM were diagnosed over a 2-year study period. Of these, 32 had adequate perilesional tissue for evaluation (AVM, 24; CCM, 8). Seizures at presentation was seen in 12/24 (50%) of AVM and 5/8 (62.5%) CCM. In AVM, hemosiderin deposition and gliosis in parenchyma (p=0.01) had significant association with seizure. Siderotic vessels in the adjacent cortex was exclusively seen only in CCM with seizures (p=0.018). Angioarchitectural features of CVM on imaging and neuronal alterations in adjacent cortex on histology failed to show any statistically significant difference between the two groups (p>0.05). CONCLUSIONS: We propose that changes in adjacent cortex appear to be epileptogenic rather than the malformation per se. Reactive gliosis and hemosiderin deposits in perilesional tissue in AVM and siderotic vessels in CCM were associated with seizure. This explains the better outcomes following extended lesionectomy that includes epileptogenic perilesional tissues.