Plasma neurofilament light chain in pediatric hereditary spastic paraplegia

Plasma neurofilament light chain (pNfL) is increasingly investigated as a biomarker of axonal damage in several neurological disorders, including hereditary spastic paraplegias (HSPs). Currently, very few studies are focused on pediatric HSPs.

Plasma NfL levels were measured in 40 pediatric (e.g., <18 years) subjects affected by genetically solved or unsolved HSPs. For 31 subjects, longitudinal NfL evaluation was also available. Potential correlation between pNfL and disease-specific or non-specific features were explored.

Median age at enrollment was 11.53 years, with a median disease duration of 9 years and a median NfL level of 8.5 pg/mL. At baseline, pNfL did not differ across SPG, vs non-SPG HSPs, GMFCS levels, pure vs complex phenotype (with a non-statistically significant increase in the latter) and early- vs childhood-onset forms. Higher levels were observed in subjects with shorter disease duration from onset. Genetically unsolved individuals exhibited non-significant reduced levels compared with genetically confirmed cases. Plasma NfL presented a similar age-related trajectory as in the healthy pediatric population, with a possible trend of increase in younger children. Finally, no differences were observed at longitudinal NfL evaluation after a median period of 9 months.

This study is the first pediatric-focused work exploring utility of pNfL in HSPs. NfL levels showed a tendency of increase especially in complex forms, in younger subjects and with shorter disease duration from onset. Lower levels were observed in genetically unsolved individuals. Larger and longer studies are warranted to further define NfL utility as a clinically relevant biomarker in pediatric HSPs.