Abstract
BACKGROUND: Infantile-onset ascending hereditary spastic paralysis (IAHSP), caused by bi-allelic variants in ALS2, is an ultra-rare, neurodegenerative disorder characterized by progressive ascending spasticity and weakness with bulbar dysfunction. OBJECTIVES: To investigate baseline plasma neurofilament light chain (NfL) levels in children with IAHSP patients compared to age-matched controls. METHODS: Five patients (age range: 6-11 years) with genetically confirmed IAHSP and 74 healthy controls were assessed. Plasma NfL was measured using a single-molecule array. Statistical analyses included non-parametric tests, age-matched comparisons, and effect size estimation. RESULTS: Children with IAHSP had modestly but significantly elevated plasma NfL levels compared to controls (median: 17.5 vs. 4.78 pg/mL, p = 0.004). High NfL levels persisted across varying levels of clinical severity. CONCLUSIONS: Plasma NfL levels are elevated in IAHSP, suggesting axonal degeneration. These pilot findings highlight NfL as a potential marker for disease activity, warranting further investigation in larger cohorts and longitudinal studies.