What is the most likely diagnosis for a large right‑sided T2/FLAIR hyperintense brain lesion with patchy contrast enhancement and no diffusion restriction involving the corona radiata, internal capsule, lentiform nucleus, thalamus, and crus cerebri, and what is the appropriate treatment?

Tumefactive Demyelinating Lesion (Acute Demyelination) is the Most Likely Diagnosis

Based on the imaging characteristics—large T2/FLAIR hyperintense lesion with patchy contrast enhancement, no diffusion restriction, and involvement of deep gray matter structures—combined with bilateral anterior visual pathway dysfunction on VEP, this presentation is most consistent with tumefactive demyelinating disease, and the current treatment with high-dose methylprednisolone is appropriate.

Diagnostic Reasoning

Why This is Likely Demyelination (Not Tumor or Infection)

The imaging features strongly favor demyelination over other diagnoses:

• Absence of diffusion restriction: This is critical. High-grade gliomas, lymphomas, and abscesses typically show restricted diffusion 1. The lack of restriction argues strongly against these entities.

• Patchy contrast enhancement pattern: While tumors can enhance, the patchy pattern described is more characteristic of active demyelination. Primary CNS lymphoma typically shows homogeneous enhancement, and glioblastoma shows ring enhancement with central necrosis 2.

• Deep gray matter involvement: The involvement of lentiform nucleus, thalamus, and internal capsule in a confluent pattern is atypical for primary brain tumors but can occur in demyelinating disease 3.

• Bilateral anterior visual pathway dysfunction: This VEP finding suggests demyelinating disease affecting the optic pathways, which is characteristic of multiple sclerosis spectrum disorders 4, 5.

Tumefactive Demyelination vs. ADEM

The distinction between tumefactive MS and ADEM is important:

• Tumefactive demyelination typically presents as a large (>2 cm) solitary or dominant lesion with incomplete ring enhancement, minimal mass effect for size, and can show patchy enhancement 5.

• ADEM usually presents with multifocal bilateral lesions, often symmetric, with deep gray matter involvement, and typically follows a monophasic course 3.

Your case shows features of both, but the unilateral dominant lesion with deep gray matter involvement and the patchy enhancement pattern favor tumefactive demyelination. The normal spine MRI (except degenerative changes) makes typical MS less likely but doesn't exclude it.

Critical Next Steps

1. CSF Analysis is Essential

You must obtain cerebrospinal fluid analysis to:

• Exclude infection (cell count, protein, glucose, cultures)
• Look for oligoclonal bands (present in >90% of MS cases)
• Rule out autoimmune/inflammatory conditions
• Consider JC virus PCR if there's any immunosuppression history (though imaging doesn't favor PML) 1

2. Consider Brain Biopsy if Diagnosis Remains Uncertain

If there's no clinical improvement after 5-7 days of high-dose steroids, or if CSF is non-diagnostic, brain biopsy should be strongly considered 3. This is particularly important because:

• Lymphoma can occasionally mimic demyelination 2
• Rare infections (Whipple's disease, lymphomatoid granulomatosis) can present similarly 6, 7
• Tissue diagnosis changes management fundamentally

3. Imaging Follow-up Protocol

Repeat MRI in 4-6 weeks after steroid treatment 5:

• Tumefactive demyelination should show significant reduction in size and enhancement
• Tumor would show progression or minimal change
• Use same sequences: T2/FLAIR, T1 post-contrast, DWI, and consider susceptibility-weighted imaging 5

Treatment Approach

Current Treatment is Appropriate

The regimen of:

• Intravenous methylprednisolone (typically 1g/day for 3-5 days) is first-line for acute demyelination 3
• Mycophenolate mofetil (MMF) and hydroxychloroquine (HCQS) suggest consideration of autoimmune/inflammatory etiology

If Steroid Response is Poor

Second-line options include 3:

• Plasma exchange (5-7 sessions over 10-14 days)
• Cyclophosphamide
• Rituximab
• Continue MMF with slow steroid taper

Critical Monitoring

• Clinical assessment every 24-48 hours: Look for improvement in neurological deficits
• Repeat MRI at 4-6 weeks: Document response to treatment 3, 5
• Watch for steroid-related complications: Hyperglycemia, infection, psychiatric symptoms

Common Pitfalls to Avoid

1. Don't assume tumor without tissue diagnosis: The imaging features are NOT specific enough for glioblastoma despite the radiologist's differential 8, 9.

2. Don't stop steroids abruptly: If this is CAA-related inflammation (less likely given age and imaging), abrupt cessation increases relapse risk significantly (HR 4.68) 3.

3. Don't delay CSF analysis: This is essential for diagnosis and cannot be replaced by imaging alone 3, 5.

4. Don't ignore lack of clinical improvement: If no improvement after 5-7 days of high-dose steroids, strongly reconsider the diagnosis and pursue biopsy 3.

Differential Diagnosis Considerations

Less Likely but Must Exclude:

• Primary CNS Lymphoma: Would typically show homogeneous enhancement and restricted diffusion 2
• Progressive Multifocal Leukoencephalopathy (PML): Requires immunosuppression history, shows subcortical U-fiber involvement, typically no enhancement 1
• CAA-related inflammation: Typically older patients (>50), lobar hemorrhages on susceptibility imaging, asymmetric confluent FLAIR hyperintensities 3
• High-grade glioma: Would show restricted diffusion, ring enhancement with central necrosis 8, 9

The normal nerve conduction study excludes peripheral nervous system involvement, supporting a central demyelinating process.

Proceed with CSF analysis immediately, continue current immunosuppression, and plan for repeat imaging in 4-6 weeks. If no clinical improvement within one week or diagnostic uncertainty persists, pursue stereotactic brain biopsy.