What do the magnetic resonance imaging findings of abnormal signal in the right frontal and frontoparietal white matter, bilateral corpus callosum involvement, an 8 × 6 mm strongly enhancing lesion at the isthmus of the corpus callosum protruding into the ventricle, and enhancing lesions with diffusion restriction in the left midbrain and pons indicate?

Interpretation of MRI Findings: Likely Inflammatory Demyelinating Disease

These MRI findings are most consistent with an inflammatory demyelinating disorder, with the differential diagnosis including multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis (ADEM), or less commonly, primary CNS vasculitis or lymphoma.

Key Diagnostic Features Present

Corpus Callosum Involvement

• The bilateral corpus callosum involvement with an 8×6 mm enhancing lesion at the isthmus protruding into the ventricle raises specific diagnostic considerations. 1
• Intra-callosal "snowball" lesions (rounded, centrally located in corpus callosum) are characteristic of Susac syndrome, though this typically presents with multiple such lesions 1
• "Cloud-like," poorly marginated corpus callosum lesions with marbled pattern suggest NMOSD 1
• Extensive posterior corpus callosum involvement with bilateral diencephalic hyperintense lesions is a "red flag" for NMOSD rather than multiple sclerosis 1

Brainstem Lesions with Enhancement

• The enhancing lesions in the left midbrain (mesencephalon) and pons with diffusion restriction are concerning for active inflammatory demyelination. 1
• Punctate or miliary enhancement in the brainstem suggests CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids), vasculitis, PML, or Susac syndrome 1
• Periaqueductal lesions in the midbrain are a "red flag" for NMOSD 1
• Multiple sclerosis typically causes peripheral pontine lesions near cisterns or floor of fourth ventricle, not central symmetric lesions 1

Diffusion Restriction Pattern

• Areas of restricted diffusion indicate acute cellular injury and active disease, distinguishing this from chronic ischemic changes. 2
• The peripheral DWI hyperintense rim (70% of atypical inflammatory demyelinating lesions) with open-rim enhancement (75%) argues strongly for demyelinating pathology over neoplasm 2
• Diffusion restriction in demyelinating lesions can persist for months to years, unlike acute stroke 1

Enhancement Pattern

• Post-contrast enhancement throughout multiple regions indicates active blood-brain barrier breakdown and ongoing inflammation. 1
• Large or multiple closed-ring enhancement suggests ADEM or malignancy 1
• Persistence of enhancement beyond 3 months raises concern for malignancy 1

Critical Differential Diagnosis

Most Likely: Inflammatory Demyelinating Disease

The combination of bilateral corpus callosum involvement, brainstem lesions with enhancement, and diffusion restriction in a multifocal distribution strongly favors inflammatory demyelination over vascular or neoplastic etiologies. 1, 2

NMOSD vs. Multiple Sclerosis

• NMOSD features that match this case: extensive corpus callosum involvement, brainstem (especially periaqueductal) lesions, cloud-like enhancement pattern 1
• Multiple sclerosis features present: multifocal white matter involvement, corpus callosum lesions, infratentorial involvement 1
• Key distinguishing test needed: Serum aquaporin-4 (AQP4) antibodies and MOG antibodies 1

Less Likely but Important Alternatives

• Susac syndrome: Consider if there are multiple intra-callosal "snowball" lesions, though typically presents with hearing loss, visual changes, and encephalopathy 1
• CLIPPERS: Punctate pontine enhancement responsive to steroids, but typically more symmetric 1
• Primary CNS lymphoma: Can mimic demyelination but typically shows persistent enhancement >3 months and different diffusion characteristics 1
• Cerebral small vessel disease: Excluded by the presence of enhancement, diffusion restriction, and corpus callosum involvement 3, 4

Immediate Diagnostic Workup Required

Serological Testing

• Obtain serum AQP4-IgG and MOG-IgG antibodies immediately to distinguish NMOSD from multiple sclerosis, as treatment differs significantly 1
• Complete autoimmune panel including ANA, anti-dsDNA, complement levels, antiphospholipid antibodies (for CNS vasculitis/lupus) 1

Cerebrospinal Fluid Analysis

• Lumbar puncture with CSF analysis for: oligoclonal bands (present in MS, typically absent in NMOSD), cell count, protein, glucose, cytology 1
• CSF elevated protein without elevated WBCs suggests inflammatory CAA or NMOSD 1

Complete Spine MRI

• Obtain cervical, thoracic, and lumbar spine MRI with and without gadolinium 1
• Longitudinal extensive transverse myelitis affecting ≥3 vertebral segments is characteristic of NMOSD 1
• Short segment spinal cord lesions (<2 vertebral segments) favor multiple sclerosis 1

Ophthalmologic Evaluation

• Assess for optic neuritis: long optic nerve lesions involving posterior nerve and chiasm suggest NMOSD or anti-MOG disease 1
• Retinal vasculitis or branch retinal artery occlusions suggest Susac syndrome 1

Clinical Implications and Prognosis

Morbidity and Mortality Considerations

The presence of brainstem lesions with diffusion restriction indicates acute injury to critical structures controlling consciousness, respiration, and motor function, requiring urgent treatment to prevent permanent disability or death. 1, 2

• Brainstem demyelination can cause respiratory failure, dysphagia, and locked-in syndrome 1
• NMOSD attacks are typically more severe than MS relapses and cause greater permanent disability if untreated 1
• Early aggressive immunotherapy improves outcomes in inflammatory demyelinating diseases 2

Treatment Urgency

Initiate high-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) immediately while awaiting definitive diagnosis, as delay worsens outcomes in all inflammatory demyelinating conditions. 1, 2

• If NMOSD is confirmed, plasma exchange should be added if steroids fail 1
• Long-term immunosuppression differs dramatically between MS (disease-modifying therapies) and NMOSD (rituximab, eculizumab) 1

Common Diagnostic Pitfalls to Avoid

Do Not Assume Vascular Disease

The presence of enhancement and diffusion restriction in a young patient with multifocal lesions excludes typical cerebral small vessel disease, which shows non-enhancing, chronic white matter changes without acute diffusion abnormalities. 3, 4

Do Not Delay Biopsy if Diagnosis Remains Uncertain

If serologies are negative and CSF is non-diagnostic, brain biopsy may be necessary to exclude lymphoma or atypical infection, as these require fundamentally different treatment. 2

• Atypical inflammatory demyelinating lesions show macrophages throughout, extensive demyelination, axonal preservation, and preserved aquaporin-4 staining 2
• Biopsy should target the most accessible enhancing lesion 2

Do Not Use Interferon-Beta in NMOSD

If AQP4 antibodies are positive, avoid interferon-beta and natalizumab, as these worsen NMOSD and increase attack frequency. 1