What investigations are indicated for a 40‑year‑old man who had influenza three weeks ago and now presents with one week of acute myelitis?

Investigations for Acute Myelitis Following Influenza Infection

Obtain an urgent contrast-enhanced MRI of the entire spine immediately as the first-line investigation to confirm myelitis, define lesion extent, exclude surgical emergencies like epidural abscess, and guide further diagnostic workup. 1

Immediate Imaging

• Perform whole-spine MRI with and without gadolinium contrast as the mandatory initial study, since multilevel involvement occurs in approximately 51% of spinal infections and skip lesions appear in 8% of cases 1
• Contrast enhancement is essential to reveal characteristic infection-related patterns, abscess formation, meningeal involvement, and to differentiate infectious from autoimmune etiologies 2, 1
• Do not delay MRI while awaiting laboratory results—timely imaging is critical to identify spinal cord compression or epidural abscess requiring emergent neurosurgical intervention 1
• Single-level imaging is inadequate; the entire spine must be visualized to detect multifocal disease 1

Laboratory Investigations (Pre-Treatment)

Blood Tests

• Draw two sets of blood cultures from separate sites before starting any antimicrobials to maximize pathogen recovery 1
• Measure inflammatory markers: ESR and CRP—a CRP >100 mg/L strongly suggests active spinal infection and is more sensitive than white blood cell count 2, 1
• Complete blood count with differential—note that up to 40% of spinal infections present with normal WBC, so a normal count does not exclude infection 1
• Screen for HIV, diabetes mellitus, and immunosuppressive conditions as these are major risk factors for infectious myelitis 2, 1

Autoimmune Serology

• Test for anti-aquaporin-4 (AQP4) antibodies using cell-based assay to evaluate for neuromyelitis optica spectrum disorder (NMOSD), particularly given the post-influenza timing 3, 4, 5
• Test for anti-MOG (myelin-oligodendrocyte glycoprotein) antibodies using cell-based assay only—ELISA has poor specificity and should not be used 2, 3, 4
• Consider testing both AQP4 and MOG antibodies in parallel if resources permit, as influenza-associated myelitis can trigger MOG-antibody positive longitudinally extensive transverse myelitis 3, 4

Cerebrospinal Fluid Analysis

• Perform lumbar puncture unless contraindicated (raised intracranial pressure with brain shift, coagulopathy, or thrombocytopenia) 2
• CSF studies should include:
  • Cell count with differential (neutrophilic pleocytosis or WCC >50/μL suggests MOG-EM or NMOSD rather than MS) 3
  • Protein and glucose with CSF/serum glucose ratio 2
  • Oligoclonal bands (absence in 87-88% of MOG-EM patients helps distinguish from multiple sclerosis) 3
  • Viral PCR panel including HSV-1/2, VZV, enterovirus, and influenza A/B PCR given the recent flu history 2, 6
  • Bacterial and fungal cultures 2
  • Cytology and flow cytometry 2

Additional Investigations Based on Clinical Context

If Infectious Etiology Suspected

• Obtain serologic testing for endemic pathogens (Mycobacterium tuberculosis, Brucella, Coccidioides, Schistosoma) based on geographic exposure risk 2, 1
• Consider image-guided biopsy if tuberculosis is suspected (large paraspinal abscess disproportionate to bone destruction) before starting anti-tubercular therapy 1

If Autoimmune/Post-Infectious Etiology Suspected

• Antinuclear antibodies (ANA), extractable nuclear antigen (ENA), double-stranded DNA antibodies 2
• Complement levels (C3, C4), lupus anticoagulant, cardiolipin antibodies 2
• Antithyroid antibodies (thyroglobulin, thyroperoxidase) 2
• Voltage-gated potassium channel complex antibodies and NMDA receptor antibodies if encephalitic features present 2

Critical Timing Considerations

• Delay empiric antimicrobial therapy until after blood cultures and CSF are obtained unless the patient is hemodynamically unstable, septic, or has rapid neurologic decline 1
• If empiric therapy is required immediately, initiate vancomycin (MRSA coverage) plus third- or fourth-generation cephalosporin (gram-negative coverage) and add acyclovir for HSV/VZV coverage 1
• For post-infectious/autoimmune myelitis, high-dose intravenous methylprednisolone (1,000 mg daily for 5 days) is first-line treatment and should not be delayed once infection is excluded 3, 6

Red Flags Requiring Immediate Neurosurgical Consultation

• New or worsening motor weakness, ascending sensory level, or bowel/bladder dysfunction 1
• MRI evidence of epidural abscess or significant spinal cord compression 2, 1
• Spinal instability or pronounced kyphotic deformity 1

Common Pitfalls to Avoid

• Do not assume a normal white blood cell count excludes infection—inflammatory markers (CRP, ESR) are more reliable 1
• Do not start antibiotics before obtaining cultures/CSF unless the patient meets instability criteria, as premature therapy markedly reduces diagnostic yield 1
• Do not use ELISA for MOG antibody testing—only cell-based assays are acceptable 2, 3
• Do not limit imaging to the symptomatic level—whole-spine MRI is mandatory 1