Exploratory Analysis of Neuroimaging and Molecular Findings in a Cohort of Neuronal Ceroid Lipofuscinosis: a Descriptive study

Neuronal ceroid lipofuscinosis (NCL) is a group of progressive neurodegenerative disorders affecting the brain and retina. This study descriptively characterizes Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (^1H MRS) features across NCL subtypes in 16 patients and preliminarily explores potential associations with clinical severity and genetic findings. Due to the small sample size, no definitive genotype–phenotype correlations could be established; rather, we report observed imaging patterns as hypothesis-generating observations. MRI demonstrated patterns such as thalamic T2-weighted hypointensity and periventricular white matter signal abnormalities, which may reflect disease burden and progression. ^1H MRS, performed in a subset of patients, showed reduced N-Acetyl Aspartate and variable choline peaks. Notably, preliminary subtype-specific metabolic trends were observed across the four subtypes in which MRS was performed, suggesting the potential for metabolite profiling to aid in diagnosis and subtype differentiation. However, these findings are merely exploratory and require validation in larger cohorts. These preliminary findings suggest a complementary role for advanced neuroimaging alongside molecular testing in the early diagnosis and evaluation of NCL, though larger prospective studies are needed to validate these observations.