Abstracts

Rationale: Sturge-Weber syndrome (SWS) is a sporadic congenital neurocutaneous disorder characterized clinically by facial port-wine stain in the distribution of the trigeminal nerve and intractable epilepsy associated with meningeal angiomatosis, a type of vascular malformation. Coexistent cortical neuronal dyslamination associated with vascular malformation is histopathologically designated as focal cortical dysplasia (FCD) type IIIc in the ILAE classification; however, its pathological and functional significance in the epileptogenicity as well as histogenesis remain elusive. To elucidate the possible pathogenesis of SWS-related FCD type IIIc, we performed histological and immunohistochemical evaluations of cortical dyslamination in surgically resected brain tissue from patients with SWS. Methods: Six surgically resected brain tissues from patients with SWS were retrospectively chosen for this study from archival paraffin blocks (age 2.5-45 years at operation; mean 21.8+-18.5 years). Serial sections were subjected to Luxol Fast Blue - Hematoxylin - Eosin (LFB-HE), and elastica Masson stainings along with immunostainings for NeuN (clone A60, Chemicon Temecula, CA, USA), non-phosphorylated neurofilament H (clone SMI32, BioLegend, San Diego, CA, USA), and GFAP (clone 6F2, Dako, Glostrup, Denmark; clone GA5, Newcastle Upon Tyne, UK). Neuronal population and arrangement as well as astrogliosis in the cerebral neocortex were evaluated in the area with no or subtle, if any, calcification. Results: Focal horizontal bands showing neuronal loss and astrogliosis of varying thickness and depth were observed in all 6 cases. In 5 of 6 cases, this pseudolaminar lesion was localized in cortical layer (L) 3 affecting superficial or deeper portion or entire thickeness, extending to the neighboring L2 and/or L4. In one case having hippocampal sclerosis (dual pathology), pseudolaminar lesion was confined to L5. In 2 cases, the thickness and depth of the lesion was variable within a given section. Neither fresh ischemic change nor old cystic infarct was observed in all cases. There was no dysmorphic neuron or balloon cell. Overall, there appears to be a selective vulnerability for tissue injuries showing the most severe neuronal loss in L3 followed by L4 or less frequently L2 or both, with relative sparing of L5 and L6 (Table). Vascular congestion was observed in both meningeal angiomatosis and parenchymal, often dilated, veins in all cases. Cortical calcification of tram-track pattern, mainly affecting L2 and L4, was observed in all but one case aged 2.5 at operation. Numerous small calcospherites were often accentuated on wall of capillary or postcapillary venule. Conclusions: Pseudolaminar neuronal loss and astrogliosis affecting particularly cortical L3 and L4 appears to be the most frequent pattern of cortical dyslamination that characterize FCD type IIIc associated with meningeal angiomatosis in SWS. Chronic focal hypoxic-ischemic injury putatively due to venous stasis associated with meningeal angiomatosis may play a role in the pathogenesis of SWS-related FCD type IIIc. Funding: No funding