What investigations and management are needed for a 40-year-old female with recent history of influenza, presenting with subacute bilateral lower limb numbness and weakness, and MRI showing multiple eccentric intramedullary short segment suspected demyelinating lesions at the cervical and thoracic spine?

Diagnostic Workup for Suspected Post-Infectious Transverse Myelitis with Demyelinating Features

This patient requires immediate brain MRI with contrast, lumbar puncture with comprehensive CSF analysis including oligoclonal bands and aquaporin-4 antibodies, and high-dose intravenous methylprednisolone should be initiated urgently while awaiting confirmatory testing. 1, 2

Immediate Neuroimaging

Brain MRI with Contrast

• Perform brain MRI with gadolinium immediately to assess for dissemination in space, which is critical for distinguishing between monophasic acute disseminated encephalomyelitis (ADEM), multiple sclerosis, and neuromyelitis optica spectrum disorder (NMOSD). 1, 2
• Brain involvement occurs in up to 70% of NMOSD patients and can show nonspecific white matter lesions or specific patterns involving periventricular, brainstem, or diencephalic regions. 1
• The presence of large, bilateral, asymmetric subcortical lesions would favor ADEM, while perivenular lesions suggest MS, and specific brainstem/diencephalic patterns suggest NMOSD. 1, 3

Spinal Cord MRI Review

• The existing spine MRI showing multiple eccentric short-segment lesions needs careful interpretation—longitudinally extensive transverse myelitis (LETM) extending over 3+ contiguous segments strongly suggests NMOSD rather than MS. 1
• Short-segment eccentric lesions are more typical of MS, but post-infectious myelitis can present with variable patterns. 1

Cerebrospinal Fluid Analysis

Essential CSF Studies

• Perform lumbar puncture urgently (unless contraindicated by mass effect or coagulopathy) with the following tests: 1, 2
  • Cell count with differential (expect lymphocytic pleocytosis in inflammatory conditions)
  • Protein and glucose levels
  • Oligoclonal bands (present in 85-95% of MS but often absent in ADEM and NMOSD) 1, 3
  • Viral PCR panel including influenza, HSV, VZV, enterovirus 1, 2
  • Bacterial and fungal cultures to exclude infectious myelitis 1
  • Cytology to exclude malignancy 1

Contraindications to Immediate LP

• If clinical signs suggest raised intracranial pressure (papilledema, altered consciousness, focal deficits suggesting mass effect), obtain CT head first. 1
• In anticoagulated patients, reverse adequately before LP; for bleeding disorders, provide replacement therapy. 1

Serological Testing

Autoimmune and Demyelinating Disease Panel

• Serum aquaporin-4 IgG antibodies (AQP4-IgG): Critical for diagnosing NMOSD—positive in 60-80% of cases and highly specific. 1, 4
• Serum MOG (myelin oligodendrocyte glycoprotein) antibodies: Increasingly recognized in post-infectious demyelination and seronegative NMOSD. 1
• ANA, anti-dsDNA, anti-Ro/La, complement levels (C3, C4) to evaluate for systemic lupus erythematosus with neuropsychiatric manifestations. 1
• Antiphospholipid antibodies if thrombotic myelopathy is considered. 1

Infectious and Inflammatory Markers

• ESR, CRP, complete blood count with differential 1
• Blood cultures if fever or systemic infection suspected 1
• Influenza serology (IgM and IgG) to confirm recent infection 4, 5
• Vitamin B12, HIV, RPR, thyroid function tests 1

Additional Diagnostic Studies

Electrodiagnostic Testing

• Visual evoked potentials to detect subclinical optic nerve involvement, which would support NMOSD or MS over isolated myelitis. 1
• Somatosensory evoked potentials may help localize lesions and assess functional impairment. 1

Ophthalmologic Examination

• Funduscopy to evaluate for optic disc edema or atrophy, as optic neuritis occurs in 21-48% of NMOSD cases with myelitis. 1, 4

Critical Diagnostic Distinctions

Post-Infectious ADEM vs. MS vs. NMOSD

• ADEM features: Monophasic illness, recent infection (influenza), encephalopathy, large bilateral asymmetric lesions on brain MRI, negative oligoclonal bands, pediatric predominance but can occur in adults. 1, 3, 6, 5
• MS features: Relapsing course, perivenular lesions, positive oligoclonal bands (85-95%), Dawson fingers on MRI, short-segment eccentric spinal cord lesions. 1
• NMOSD features: LETM (≥3 segments), positive AQP4-IgG, area postrema involvement, severe attacks with poor recovery, negative or low oligoclonal bands. 1, 4

Post-Influenza Demyelination

• Influenza A has been specifically associated with both ADEM and monophasic NMO in the literature, typically occurring 3-9 days post-infection. 4, 6, 5
• Post-infectious cases are more likely to be monophasic, AQP4-antibody negative, and have better prognosis with early treatment. 4

Immediate Management Considerations

Empiric Treatment While Awaiting Results

• Initiate intravenous methylprednisolone 1 gram daily for 3-5 days immediately given the severity of bilateral lower limb involvement and multiple spinal cord lesions. 1, 3
• If severe or rapidly progressive, consider adding IVIG 2 g/kg over 5 days concurrently. 1
• Do not delay corticosteroids while awaiting diagnostic confirmation—early treatment (within hours to days) significantly improves neurological outcomes in transverse myelitis. 1

Red Flags Requiring Urgent Intervention

• Rapidly ascending weakness suggesting Guillain-Barré syndrome overlap
• Sphincter dysfunction or urinary retention requiring catheterization 1
• Respiratory muscle weakness necessitating ICU monitoring 1
• MRI evidence of cord compression or swelling causing mass effect 1

Common Pitfalls to Avoid

• Do not wait for oligoclonal band results to initiate treatment—delay beyond 2 weeks significantly worsens prognosis in inflammatory myelitis. 1
• Do not assume MS based solely on multiple lesions—post-infectious ADEM can present with multifocal involvement and requires different prognostic counseling. 1, 3
• Do not miss NMOSD by focusing only on AQP4 antibodies—20-40% are seronegative, and clinical/MRI criteria alone may establish diagnosis. 1
• Do not overlook infectious myelitis—viral PCR and cultures are essential as HSV, VZV, and enterovirus can mimic demyelinating disease and require specific antiviral therapy. 1, 2