Does checking anti-MOG (myelin oligodendrocyte glycoprotein) antibodies in both cerebrospinal fluid (CSF) and serum provide additional diagnostic information?

Anti-MOG Antibody Testing: Serum Only is Recommended

Routine CSF testing for anti-MOG antibodies does not provide additional diagnostic value and is not recommended—serum testing alone is the standard of care. 1

Why Serum Testing is Sufficient

MOG-IgG is produced extrathecally (outside the CNS), making serum the optimal specimen for detection. 2 The international consensus guidelines explicitly list "MOG-IgG positivity in the CSF but not in the serum" as a diagnostic "red flag" that should prompt physicians to challenge the result and consider retesting. 1

Key Evidence Against Routine CSF Testing

• CSF-only positivity is considered atypical and unreliable because MOG antibodies are typically produced systemically rather than intrathecally, unlike antibodies in multiple sclerosis. 1

• The only valid exception is the rare circumstance where co-existing serum autoantibodies interfere with serum analysis but not CSF analysis, causing a false-negative serum test. 1

• Province-wide testing data from Alberta (2017-2023) found that among 268 patients with paired serum/CSF samples, zero patients had CSF-positive/serum-negative results—all CSF-positive patients were also serum-positive. 3

When CSF Testing Might Be Considered

While not routinely recommended, CSF testing may have limited utility in specific scenarios:

Seronegative Patients with High Clinical Suspicion

• A small retrospective study found CSF MOG antibodies in 3 of 80 seronegative patients (4% overall, 7% excluding MS patients), including 2 with NMOSD and 1 with ADEM. 4

• However, this represents a very small subset and the clinical significance remains uncertain, as larger real-world data from Alberta found no seronegative/CSF-positive cases. 3

Timing Considerations

• If initial serum testing is negative but MOG-EM remains suspected, retesting serum during acute attacks or during treatment-free intervals is more appropriate than CSF testing. 1

• MOG-IgG concentrations are higher during acute attacks than remission and lower during immunosuppression, so timing of serum collection matters more than specimen type. 1, 2

Practical Algorithm for MOG Antibody Testing

1. Order serum MOG-IgG by cell-based assay using full-length human MOG with Fc-specific secondary antibodies (gold standard). 2

2. If serum is positive: Diagnosis confirmed; no CSF testing needed. 1, 2

3. If serum is negative but clinical suspicion remains high:

   • Retest serum during acute relapse (not CSF). 1
   • Retest serum 1-3 months after plasma exchange if recently treated. 1
   • Consider alternative diagnoses before pursuing CSF testing. 1

4. CSF testing should only be considered if serum remains negative despite optimal timing AND there is concern for interfering serum autoantibodies. 1

Common Pitfalls to Avoid

• Do not routinely order CSF MOG antibodies as part of initial workup—this wastes resources and may generate confusing false-positive results. 1, 3

• Do not interpret isolated CSF positivity as diagnostic—this is a red flag requiring retesting with an alternative assay and expert consultation. 1

• Do not test CSF in patients with optic neuritis—the Alberta study found zero CSF-positive cases among optic neuritis patients, even when seropositive. 3

• Remember that CSF findings in MOG-EM can mimic CNS infection with neutrophilic pleocytosis (up to 306 cells/μL) and lack of oligoclonal bands, but this does not indicate the need for CSF antibody testing. 1