Neuronal ceroid lipofuscinosis: a clinicopathological study

Abstract

We report the clinical, electrophysiological, radiological and morphological features in a series of 12 patients of histopathologically confirmed cases (infantile, juvenile and adult onset) of neuronal ceroid lipofuscinosis (NCL) observed from 1979 to 1998 at National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore (South India). The commonest type of NCL was juvenile ( n=8, 67%) while infantile and adult forms were two each ( n=2, 16.8%). The age at presentation ranged from 2 to 45 years (mean—12.6, 14.3 years; median—7 years; M:F ratio of 2:1). Four patients (33%) had positive family history and five patients had history of consanguineous parentage (41.6%). The commonest presenting symptoms were regression of milestones (83.3%) and/or seizures, myoclonus (83.8%) followed by involuntary choreiform movements (50%), visual loss (41.6%), ataxia (33.3%) and abnormal behaviour (16.6%). Neuro-ophthalmological abnormalities like optic atrophy (50%), macular degeneration (33.3%) and retinitis pigmentosa (8.3%) were seen in two thirds. Nerve conduction studies ( n=4) revealed abnormalities in two, suggestive of sensorimotor neuropathy. Scalp EEG ( n=9) showed slowing of background activity (BGA) of varying degrees with paroxysmal bursts of seizure discharges in majority. Cranial CT scan ( n=4) revealed varying degrees of diffuse atrophy. Diagnostic brain biopsy was carried out in 11 and brain was examined at autopsy in 1 case. Histological examination revealed characteristic PAS and Luxol Fast Blue (LFB) positive, autofluorescent (AF) intracellular ceroid material, both in neurons and astrocytes in the grey matter. Electron microscopy ( n=5) revealed curvilinear ( n=4), lamellar ( n=2) and electron dense ( n=2) inclusions in neurons, astrocytes and vascular endothelial cells. To conclude, this neurodegenerative disease had varied but characteristic clinical presentations and required histopathological confirmation of diagnosis.