Figure 5.

Neuropathological hallmarks of the c.1197−8G>A (GenBank: NM_001288739.1) variant

(A and B) Brain macroscopic aspect. (A) White matter displayed severe atrophy with lateral ventriculomegaly, spindly gyri, and extremely thin corpus callosum. A central myelin discoloration was observed consisting of a myelin defect sparing U fiber. (B) Among gray structures, thalamus was severely atrophic associated with a third ventricle distention. Cortical thickness seemed preserved but was difficult to estimate considering the associated severe white matter atrophy. CC, corpus callosum; Cx, cortex; LV, lateral ventricle; Put, putamen; Pal, pallidum; Th, thalamus; Tg, trigone; UF, U fibers; V3, third ventricles, ^∗, deep white matter.

(C–J) Pallidal synaptic dysplasia. (C) Pallidal glomeruli (star) appeared as rounded formations containing intermingled eosinophilic neurites (arrow). (D–I) After immunohistochemistry and control matching, these glomeruli (E) (star) consisted of exuberant neurites proliferation (arrow) (NF200(+)) that were covered by diffuse synaptic areas (synaptophysin). (D), (F), and (H) are age-matched controls; (F) and (G) are immunohistochemistry with anti-neurofilament 200; (H) and (I) are with anti-synaptophysin; initial magnification ×100. (J) Brain biopsy at pallidum level after electron microscopy conditioning. Initial magnification: ×7,500. Five hyperplastic synaptic terminations (Axt) surrounding one receptive dendrite (Dd). Synaptic vesicles appeared abnormally numerous and packed. M, mitochondria.