Is a patient with Multiple Sclerosis (MS) indicated for a lumbar puncture (LP) for Oligoclonal Bands (OCBs) and Anti-Myelin Oligodendrocyte Glycoprotein (Anti-MOG) testing?

Lumbar Puncture for OCBs and Anti-MOG Testing in MS Patients

Lumbar puncture for oligoclonal bands (OCBs) testing is indicated in patients with suspected MS when additional evidence is needed to confirm the diagnosis, while Anti-MOG testing should be considered specifically in patients with atypical MS presentations, particularly those with severe or bilateral optic neuritis. 1

Role of OCBs in MS Diagnosis

OCBs are a crucial diagnostic marker for MS, present in:

• 90-98% of MS patients in Central and Northern Europe
• 40-80% of Asian MS patients
• 84% of MS patients in Sardinia 1

The presence of OCBs helps distinguish MS from other neurological disorders, particularly MOG-associated disease (MOGAD), where OCBs are present in only 12-13% of cases 1.

When OCBs Testing is Indicated:

1. For patients with one attack and clinical evidence of one lesion: OCBs can help demonstrate dissemination in space when combined with MRI findings 1
2. For patients with insidious neurological progression: OCBs can substitute for MRI criteria of dissemination in space for primary progressive MS diagnosis 1
3. When MRI findings are atypical for MS: Such as normal brain MRI or absence of periventricular lesions 1

Timing of Lumbar Puncture

Recent evidence indicates that steroid treatment before lumbar puncture does not affect OCB results, allowing flexibility in diagnostic workup 1. This is supported by a 2024 retrospective study showing that initiation of intravenous methylprednisolone before LP was not associated with negative OCBs (11.8% vs. 13.5%, p = 0.721) 2.

Anti-MOG Testing Indications

Anti-MOG testing should be considered in:

• Patients with severe or bilateral optic neuritis, particularly with atypical MRI features for MS 1
• Patients with absence of CSF-restricted OCBs and optic neuritis at onset (these factors are independently associated with MOG-Ab positivity) 3
• Patients showing poor response or worsening with typical MS treatments 1

Key Differentiating Features:

• Only 12.5% of MOG-Ab+ patients have CSF-restricted OCBs compared to 61.7% of MOG-Ab- patients 3
• 52.9% of MOG-Ab+ patients have normal brain MRI at baseline versus 26.2% of MOG-Ab- patients 3
• MOG-Ab are present in only 2.7% of adults with a first demyelinating event suggestive of MS 3

Diagnostic Algorithm

1. For typical MS presentations with clear MRI evidence:

   • If McDonald criteria are fully met with MRI evidence alone, LP for OCBs may not be necessary 1

2. For patients with incomplete or atypical MRI findings:

   • Perform LP for OCBs to help establish dissemination in space 1
   • Positive OCBs support MS diagnosis
   • Negative OCBs should prompt consideration of alternative diagnoses, particularly MOGAD 1

3. For patients with optic neuritis and atypical features for MS:

   • Perform both OCBs and Anti-MOG testing 1, 3
   • If OCBs are negative and optic neuritis is present, MOG-Ab testing is strongly indicated 3

Common Pitfalls and Caveats

1. Technical considerations for OCB detection:

   • The recommended technique is iso-electric focusing in agarose gels followed by immunoblotting
   • Paired CSF and serum samples should be analyzed without dilution 1
   • Technical issues can decrease reproducibility; cell-based assays and isoelectric focusing techniques are most sensitive 1

2. Interpretation challenges:

   • The presence of "red flags" (such as borderline MOG-IgG and/or MRI lesions suggestive of MS) may indicate "possible" rather than "definite" MOG-EM 4
   • Retesting of borderline MOG-IgG results is recommended 4

3. Regional variations:

   • OCB frequency varies by region and genetic factors, with lower frequencies in Asian patients and some European regions 1

4. Prognostic value:

   • OCB positivity correlates with higher disease burden in MS
   • IgM-type OCBs are associated with a more aggressive disease course 1
   • Disease progression appears independent of OCB status 5