Lipofuscin Accumulation in Dysmorphic Neurons in FCDIIa Focal Epilepsy: A Case Report and Literature Review

We describe the case of a 29-year-old woman with focal drug-resistant epilepsy and an unusual Focal Cortical Dysplasia (FCD) IIa with lipofuscin accumulation in dysmorphic neurons. We discuss the commonalities and discrepancies between the present case and FCDIIa cases without lipofuscin accumulation at the clinical, histopathological and proteomic levels. (a) Coronal 3D-FLAIR imaging demonstrates an unusually deep F1-F2 sulcus associated with subtle signal alteration (arrowhead). (b) Coronal FDG-PET coregistered with T1 3D MRI reveals marked hypometabolism of the same sulcus (arrowhead). (c-f) Histological images of the surgical specimen show numerous dysmorphic neurons (DN), a typical hallmark of FCD type IIa. Notably, DN (green arrows) exhibit cytoplasmic PAS-positive granular material identified as lipofuscin (c), neurofilament accumulation with peculiar 'ring-like' aspect (d,e) and occasional ubiquitin-binding protein p62 labelling (f). (g-h) Matrix-assisted laser desorption/ionisation imaging mass spectrometry (MALDI-IMS) further supports differences at proteomic level between the present case and classic FCDIIa without lipofuscin accumulation.