Diagnostic Biomarkers of Neurodegeneration in Multiple Sclerosis

cerebral spinal fluid
cerebral spinal fluid
Production of intrathecal immunoglobulin G and neurofilament light chain levels may have a diagnostic value in multiple sclerosis.

A cross-sectional study examining the diagnostic power of neurodegeneration biomarkers in multiple sclerosis has identified 2 such biomarkers. Both neurofilament light chain levels and intrathecal immunoglobin G production may aid in characterizing the disease course. This study was published in PLoS One.

There were 271 participants in the study, all of whom showed symptoms of the onset of multiple sclerosis after diagnostic examination. These subjects were compared with 23 persons with progressive multiple sclerosis and 51 healthy controls. Researchers then classified participants into 4 different groups: those with early relapsing remitting multiple sclerosis (early RRMS; n=93) or clinically isolated syndrome (n=4); those with RRMS whose disease had presented for ≥ 2 years (established RRMS; n=39); those who displayed symptoms of multiple sclerosis but not the disease (symptomatic controls; n=89; and those with diseases other than multiple sclerosis (n=46).

The only biomarkers of neurodegeneration with significant diagnostic power were intrathecal production of immunoglobin G and an increased level of cerebral spinal fluid neurofilament light chain (median 670 ng/L; interquartile range 400 to 2110). Other biomarkers linked with progressive disease were thin layers of retinal nerve fiber, increased cerebral spinal fluid glial fibrillary acidic protein levels, and low brain parenchymal fractions. However, these indicators were not associated with other phenotypes. Thin layers of retinal nerve fiber and low brain parenchymal fractions also correlated with a longer duration of disease.

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Researchers conclude that “intrathecal immunoglobulin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis…This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.”


Novakova L, Axelsson M, Malmeström C, et al. Searching for neurodegeneration in multiple sclerosis at clinical onset: diagnostic value of biomarkersPLoS One. Apr 3;13(4):e0194828.