FIGURE 3.

Cobblestone pathology in the cerebral cortex. The surface contour of the cerebral cortex was pebbled in a diffuse, relatively symmetric distribution that affected all lobes in both hemispheres (A, B). Multifocal sites of dense gliosis were noted along the cerebral cortical surface (C, arrow, H&E stain; pv). A reticulin stain (D) revealed that the pial surface basement membrane was disrupted at these sites of gliosis (arrow). Large, dysmorphic neurons (either side of the arrow, D) were often present at these sites. Coronal sections further revealed that adjacent gyri were partially fused across the intervening sulci (E and F, arrows; left frontal lobe). Superficially displaced neurons were also evident with neuN immunoperoxidase staining (G); subtle abnormal clustering of neurons was also often present within upper layers of the cortex. The bracket in G marks a region of fusion between adjacent gyri; the arrow points to the sulcus. A pv is present within the sulcus. White matter from multiple sites was unremarkable (H, LFB stain; frontal lobe centrum semiovale). The scale bar in panel C is 200 µm for panels C and G, and 100 µm for panels D and H. H&E, hematoxylin and eosin; LFB, luxol fast blue; pv = pial surface vessels.