The utility of serum neurofilament light chain in MOGAD: Current insights and future directions

Serum neurofilament light chain (sNfL) has become an increasingly established biomarker for monitoring in multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a demyelinating disorder distinct from MS in terms of pathophysiology and treatment options, also presenting with demyelinating attacks that can result in permanent disability. Given its unpredictable disease course, the need for biomarkers reflective of the risk for poor clinical recovery or relapsing course is pressing. The purpose of this review is to summarize the current knowledge on sNfL levels in people with MOGAD, assess their utility for clinical practice and gain insights for future research.

Embase, MEDLINE, Scopus, and CINAHL databases were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Keywords used in the search included: (myelin oligodendrocyte glycoprotein OR MOG OR MOGAD) AND (neurofilament* OR neuro filament* OR NfL OR sNfL). This initial search generated 195 reports, 23 of which were original research articles investigating NfL levels in MOGAD patients, therefore meeting our inclusion criteria.

422 MOGAD patients were involved across all studies. Most studies revealed higher sNfL in MOGAD patients (n = 292) than in healthy controls (n = 3,172) with one study finding higher sNfL in MOGAD only during relapse. sNfL levels during attacks were similar when comparing MOGAD (n = 94) to MS (n = 256) and MOGAD (n = 149) to APQ4+ neuromyelitis optica spectrum disorder (APQ4+ NMOSD) (n = 214). MOGAD patients with brain lesions on magnetic resonance imaging (MRI) during a recent attack (n = 69 samples) had higher sNfL levels than patients without brain lesions (n = 78 samples). Median sNfL concentration was higher following clinical attacks (n = 69 samples) than in remission (n = 83 samples) in 3/5 studies. sNfL were higher at disease onset than subsequent attacks in 2 studies (n = 133 samples). Onset sNfL levels were not predictive of the likelihood of future relapse (relapsing: n = 15, monophasic: n = 18). A positive correlation was found between sNfL levels and attack severity assessed through various disability scales (n = 202), but not with the severity of acute or residual visual acuity (n = 45 eyes), or with residual retinal thickness among subjects with the optic neuritis (ON) phenotype (n = 11 eyes). The sGFAP/sNfL ratio showed utility in discriminating MOGAD from other autoimmune demyelinating diseases in two studies (MOGAD: n = 56, APQ4+ NMOSD: n = 66, MS: n = 31).

sNfL levels at presentation have limited utility in distinguishing MOGAD from other demyelinating disorders, but their combination with other biomarkers might improve their diagnostic utility. sNfL levels are higher in brain/spinal cord presentations than optic neuritis, correlating with clinical severity of these phenotypes but less so with the severity of visual outcome. Further studies should clarify the utility of sNfL as a biomarker for MOGAD, particularly in relation to long-term outcomes and imaging markers of central nervous system damage. Standardized sNfL testing parameters will improve study comparability and clinical application.