What is the likely diagnosis and management for a young to middle-aged adult with recurrent steroid-responsive internuclear ophthalmoplegia (INO) and normal MRI findings?

Recurrent Steroid-Responsive Internuclear Ophthalmoplegia with Normal MRI

The most likely diagnosis is MOG-antibody associated encephalomyelitis (MOG-EM), and you should immediately test for serum MOG-IgG antibodies using cell-based assays while initiating high-dose intravenous corticosteroids for acute episodes. 1

Primary Diagnostic Consideration: MOG-Antibody Disease

MOG-EM represents the leading diagnosis when INO is recurrent, steroid-responsive, and occurs with normal brain MRI. The 2018 international MOG encephalomyelitis guidelines specifically describe this exact clinical scenario as a high-risk presentation for MOG-IgG seropositivity 1:

• Steroid-dependence with symptom flaring after steroid taper is a hallmark feature of MOG-EM 1
• Normal brain MRI does not exclude MOG-EM, as brainstem lesions may be subtle or absent on conventional imaging 1
• MOG-EM commonly presents with isolated brainstem syndromes including INO 1

Critical Testing Protocol

Order serum MOG-IgG testing using cell-based assays (IFT/FACS) only—ELISA and Western blot are obsolete and insufficiently specific 1:

• Cell-based assays must employ full-length human MOG as target antigen 1
• Use Fc-specific or IgG1-specific secondary antibodies to avoid cross-reactivity 1
• Serum is the specimen of choice; ship at 4°C or on dry ice 1
• CSF testing is not usually required since MOG-IgG is produced extrathecally 1

Secondary Differential: Multiple Sclerosis

While MS remains a consideration in young adults with INO 2, 3, several features argue against it in this scenario:

• MS typically shows brain MRI lesions meeting dissemination in space criteria (≥1 lesion in ≥2 of 4 CNS areas: periventricular, cortical/juxtacortical, infratentorial, spinal cord) 1
• INO occurs in 16-40% of MS patients, but isolated recurrent INO with completely normal MRI is atypical 3, 4, 5
• MS is 13.89 times more likely to cause INO than NMOSD/MOG-EM, but this applies when MRI shows typical demyelinating lesions 5

When to Consider MS Despite Normal MRI

• If MOG-IgG testing is negative, obtain high-resolution T2-weighted brainstem MRI to detect subtle MLF lesions 2, 6
• Check CSF for oligoclonal bands—their presence supports MS, while absence (87-88% of MOG-EM cases) favors MOG-EM 7
• Consider that 3+ periventricular lesions combined with age or oligoclonal bands predicts MS conversion 1

Acute Management Algorithm

Initiate high-dose intravenous corticosteroids immediately for acute episodes 7:

1. Methylprednisolone 1000 mg IV daily × 3-5 days 7
2. Do not abruptly discontinue steroids—taper slowly over weeks to months to prevent relapse 1, 7
3. If inadequate response, consider plasma exchange 1

Long-Term Management Based on Serology

If MOG-IgG Positive:

• Prolonged oral prednisone taper (weeks to months) is essential to prevent relapses 7
• Consider rituximab for severe, recurrent, or steroid-refractory disease 1, 7
• Avoid interferon-beta, which may worsen MOG-EM 1

If MOG-IgG Negative and AQP4 Negative:

• Repeat high-resolution brainstem MRI with thin cuts through the pons/midbrain 2, 6
• Obtain CSF analysis for oligoclonal bands and pleocytosis 7
• Consider seronegative NMOSD or idiopathic recurrent brainstem syndrome 7
• Neurology consultation for consideration of empiric immunotherapy 2

Critical Pitfalls to Avoid

• Never use ELISA or peptide-based assays for MOG testing—only cell-based assays are acceptable 1
• Do not rapidly taper steroids in suspected MOG-EM—this precipitates relapses 1
• Do not assume MS without MRI lesions meeting dissemination in space criteria 1
• In older adults (>50 years), always consider brainstem stroke/ischemia as the primary etiology, even if recurrent 2, 6, 8

Symptomatic Management Options

If diplopia persists after 6 months despite treatment 2:

• Prism therapy for symptomatic relief 2
• Botulinum toxin injection to affected extraocular muscles 2
• Strabismus surgery (bilateral medial rectus resections with adjustable lateral rectus recessions) for disabling exotropia 9