Objective:

To evaluate serum neurofilament light (sNfL) levels in seropositive Stiff Person Syndrome Spectrum Disorders (SPSD) and compare them with neuroinflammatory cases (multiple sclerosis - MS) and healthy controls (HC).

Background:

Blood and cerebrospinal fluid (CSF) NfL levels are reliable prognostic and monitoring biomarkers of neurological injury across various neurological diseases. Here, we provide an initial exploration of sNfL levels in patients with SPSD.

Design/Methods:

sNfL was measured in people with SPSD, MS, and HC participants using a high-throughput immunoassay (Siemens Healthineers). Age-specific cut-offs of sNfL levels were calculated using the HC data. MS participants with sNfL > the age-specific 97.5th percentile of HC were classified as having elevated sNfL (sNfL-E). Additional analyses included the age-normalized sNfL z-score as a continuous variable.  

Results:

The majority of SPSD cases (n=20) were female (75%) with a median age (IQR) of 53 years old (44-58) and exhibited the classic phenotype (70%). Anti-GAD-65 antibody was present in the serum of all cases (100%) and CSF of 15 (75%). The mean sNfLz-scores in SPSD were 1.28 (SD 1.01) and 0.86 (SD 1.22) in MS cases. sNfL levels were significantly elevated compared to HC (p=4.27e-06) but not when compared to neuroinflammatory cases (p=0.179). We found significant differences between sNfL z-scores of mRS=4 and mRS=2 (p=0.0487). A negative correlation was found between the length of disease and sNfL z-score (rho=-0.46, p=0.04). 

Conclusions:

Neurofilament light chain levels were elevated in the serum of patients with SPSD compared to healthy controls and similar to MS cases. Higher sNfL levels were associated with earlier stages of the disease and higher disability scores in patients with SPSD. Further studies are needed to assess whether sNfL could be a biomarker of evolving disease burden and/or treatment response in SPSD.