Objective:

We evaluated whether neurofilament light chain (NfL) measured in paired cerebrospinal fluid (CSF) and serum is altered in spinal bulbar muscle atrophy (SBMA) and amyotrophic lateral sclerosis 4 (ALS4).

Background:

Spinal bulbar muscle atrophy and amyotrophic lateral sclerosis 4 are two rare forms of motor neuron disease that are characterized by slow disease progression.

Design/Methods:

Fourteen adult participants (7 SBMA, 4 ALS4, and 3 controls) enrolled in natural history studies at the National Institutes of Health underwent paired CSF and serum sampling. Two of the patients with SBMA were also assessed with paired CSF and blood sampling at 6 and 12 months apart. NfL concentrations in CSF and serum were measured using ultrasensitive technology (Simoa, Billerica, MA).

Results:

CSF and serum NfL were correlated (r=0.51, p=0.031). Patients with SBMA had increased concentrations of CSF NfL (median, 1133 pg/mL, IQR 206) as compared to ALS4 (median, 672 pg/mL, IQR 652) or controls (median, 686 pg/mL, IQR 1351). In contrast, serum concentrations of NfL did not differ between SBMA (median, 10 pg/mL, IQR 6), ALS4 (median, 10 pg/mL, IQR 24), or controls (median, 22 pg/mL, IQR 25). Longitudinally, only one of the SBMA patients had increased CSF (1153 pg/mL vs 1210 pg/mL) and serum NfL levels (6.1 pg/mL vs 6.6 pg/mL) at 12 months, while in the second patient both CSF (989 pg/mL vs 947 pg/mL) and serum NfL (10.3 pg/mL vs 9.3 pg/mL) were decreased at 12 months follow up.

Conclusions:

The results of this pilot study suggest patients with SBMA have increased concentrations of CSF NfL as compared to ALS4 and controls. Similar serum NfL levels could be due the slow neurodegeneration in SBMA, intact blood brain barrier, and/or small sample size. Longitudinal changes need to be assessed in a larger sample size accounting for age and sex.