Should I order cerebrospinal fluid (CSF) anti-myelin oligodendrocyte glycoprotein (MOG) testing if serum anti-MOG antibodies and oligoclonal band (OCB) testing are negative?

Should You Order CSF Anti-MOG Testing After Negative Serum Results?

No, you should not routinely order CSF anti-MOG testing when serum anti-MOG antibodies are negative, as serum is the preferred diagnostic specimen and CSF-restricted MOG-IgG has extremely low diagnostic utility with poor sensitivity (2.63%) and positive predictive value (1.97%). 1

Primary Diagnostic Approach

• Serum is the specimen of choice for MOG-IgG testing, not CSF, because MOG-IgG is produced predominantly extrathecally (outside the central nervous system). 2, 3

• The 2018 international consensus guidelines explicitly state that CSF testing is "not usually required" for MOG-IgG diagnosis. 3

• MOG-IgG positivity isolated to CSF without serum positivity is listed as an atypical finding that should prompt careful clinical re-evaluation. 2

Evidence Against Routine CSF Testing

• In a large national referral study of 1,127 patients with paired CSF/serum samples, only 7/1016 (0.7%) seronegative patients had CSF-restricted MOG-IgG. 1

• Among these 7 CSF-only positive cases, 4/7 (57%) had confirmed alternative diagnoses including three with multiple sclerosis and one with CNS vasculitis, not MOGAD. 1

• The sensitivity of CSF-restricted MOG-IgG is only 2.63% (95% CI 0.55-7.50%) and the positive predictive value is only 1.97% (95% CI 0.45-8.13%). 1

Rare Exceptions Where CSF Testing May Be Considered

CSF MOG-IgG testing may have limited utility in highly selected scenarios only:

• When serum MOG-IgG is low-positive (near cutoff) and diagnostic uncertainty exists, as CSF positivity was found in 81% of true MOGAD cases versus only 20% of false-positive serum cases. 4

• When co-existing serum autoantibodies might interfere with serum analysis but not CSF analysis (creating a false-negative serum test). 2

• When the clinical phenotype is highly suspicious for MOGAD (bilateral optic neuritis, longitudinally extensive transverse myelitis, brainstem encephalitis) but initial serum testing is negative—though retesting serum during acute attacks or treatment-free intervals is preferred. 3, 4

What To Do Instead of CSF Testing

• Retest serum MOG-IgG during acute attacks, as antibody concentrations fluctuate with disease activity and are higher during acute phases than remission. 3

• Retest serum during treatment-free intervals, as immunosuppression lowers MOG-IgG concentrations. 3

• Retest serum 1-3 months after plasma exchange or IVIG, as these treatments temporarily reduce antibody levels. 3

• Ensure proper testing methodology: MOG-IgG must be detected by cell-based assay using full-length human MOG with Fc-specific secondary antibodies, which is the gold standard. 3

Clinical Context: Negative OCB Does Not Exclude MS

• While oligoclonal bands are present in up to 98% of MS patients in Central/Northern Europe, they are found in only 12-13% of MOG-EM patients. 2

• However, positive OCB do NOT exclude MOG-EM, and negative OCB do not confirm it. 2

• OCB frequency varies by ethnicity (40-80% in Japanese MS patients, 84% in Sardinian MS patients), so absence of OCB alone should not drive MOG testing decisions. 2

Critical Pitfall to Avoid

• Do not interpret CSF-only MOG-IgG positivity as diagnostic of MOGAD without strong clinico-radiological features consistent with the disease, as the majority of such cases represent false positives or alternative diagnoses. 1

• CSF-restricted MOG-IgG is NOT a reliable diagnostic marker and should prompt consideration of alternative diagnoses including multiple sclerosis and CNS vasculitis. 1