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Serum Neurofilament Light Chain Limited in Predicting MOGAD Attacks but Correlates With Attack Severity
Key Takeaways
- sNfL levels are elevated in MOGAD patients, particularly during clinical attacks and with brain lesions, but have limited predictive value for relapse.
- sNfL levels during attacks are comparable between MOGAD, multiple sclerosis, and aquaporin-4-positive neuromyelitis optica spectrum disorder.
A review highlighted the role of serum neurofilament light chain as a potential biomarker in MOG antibody-associated disease, with findings pointing to associations with attack severity.
Giulia Fadda, MD
(Credit: Ottawa Hospital Research Institute)
A recently published systematic review reported that serum neurofilament light chain (sNfL) levels were elevated in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), particularly during clinical attacks and in those with brain lesions, but had limited ability to predict relapse or differentiate MOGAD from related demyelinating diseases.1
Published in Multiple Sclerosis and Related Disorders, the review analyzed 23 original research articles comprising data from 422 patients with MOGAD from Embase, MEDLINE, Scopus, and CINAHL databases. In most studies, sNfL levels were higher in patients with MOGAD (n = 292) than in healthy controls (n = 3172), with 1 study reporting elevated levels only during relapse.2 Additionally, patients with MOGAD who experienced recent attacks with brain lesions (samples, n = 69) had higher sNfL levels than those without lesions (samples, n = 78).
Conducted by senior author Giulia Fadda, MD, assistant professor of neurology in the Department of Medicine at the University of Ottawa, and colleagues, 3 out of 5 studies in the analysis reported higher median sNfL concentrations following clinical attacks (samples, n = 69) compared with remission (samples, n = 83). However, authors reported that onset sNfL levels did not predict relapse risk, with similar levels in relapsing (n = 15) and monophasic (n = 18) cases.
"This is an evolving and promising field. While the clinical utility of sNfL in MOGAD is not yet fully defined, its potential is increasingly recognized. sNfL levels at presentation have limited utility in distinguishing MOGAD from other demyelinating disorders, but combining them with other biomarkers may enhance diagnostic accuracy," Fadda told NeurologyLive®. "Because sNfL levels tend to rise during acute attacks compared to remission, they may help differentiate true relapses from pseudorelapses. However, their sensitivity in this context still needs to be better defined, and initial findings suggest that it might be lower in isolated optic neuritis presentations than in cases involving the brain or spinal cord. Further research is needed to clarify how sNfL levels relate to long-term outcomes and imaging markers of CNS damage in MOGAD. Standardized testing protocols will be essential to improve comparability across studies and support future clinical application."
Across the included studies in the analysis, authors noted that the sNfL levels during attacks were comparable between MOGAD (n = 94) and patients with multiple sclerosis (MS; n = 256), and between MOGAD (n = 149) and aquaporin-4-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD; n = 214). Notably in 2 studies, researchers reported that the sNfL levels were higher at disease onset than in subsequent attacks (n = 133).
READ MORE: Indirect Immunofluorescence May Aid in Detecting Anti-MOG Antibodies in NMOSD, MOGAD
"I believe it is unlikely that sNfL will play a major role in differentiating brain versus optic nerve phenotypes in MOGAD beyond what clinical assessment already provides. However, its value as a prognostic biomarker may vary by phenotype, likely being more informative in cases involving the brain or spinal cord, and less so in isolated optic neuritis, where axonal damage may be more localized and less reliably reflected in serum levels," Fadda said.
All told, a positive correlation was observed between sNfL levels and attack severity measured by disability scales (n = 202), although no such correlation was revealed with acute or residual visual acuity (eyes, n = 45) or retinal thickness among optic neuritis cases (eyes, n = 11). Authors also noted that the serum glial fibrillary acidic protein /sNfL ratio was reported as useful in distinguishing MOGAD from MS and AQP4+ NMOSD in 2 studies (MOGAD: n = 56, AQP4+ NMOSD: n = 66, MS: n = 31).
“While one of the greatest clinical utilities of sNfL in MS is as a sensitive marker of subclinical disease activity and in confirming treatment response, because subclinical attacks are rare in MOGAD, sNfL is less likely to serve that same role in this population. Instead, its main potential in MOGAD may lie in assessing attack severity and predicting the likelihood of clinical recovery," Fadda said. "Studies to date have primarily examined correlations between sNfL levels and acute-phase clinical disability scores, while their relationship between sNfL and residual neurological deficits, T2 lesion burden on MRI, or gray matter volume changes remains largely unexplored."
"These could be important for identifying patients who might benefit from more aggressive acute treatment. Predicting a relapsing disease course remains a major unmet need in MOGAD. Notably, two small studies did not found an association between higher sNfL levels at onset and relapse risk, but it remains to be determined whether longitudinal sNfL measurements during remission,and changes from that baseline, could offer greater predictive value. Interestingly, one study found that the sNfL/MOG antibody ratio could predict monophasic versus relapsing disease, a result that merits further validation," Fadda noted.
