Diagnostic Workup for Myelitis Symptoms with Normal MRI Spine
When a patient presents with myelitis symptoms but has a normal MRI of the spine, a comprehensive diagnostic workup focusing on cerebrospinal fluid analysis, serum biomarkers, and neurophysiological studies is essential to identify the underlying etiology and guide appropriate treatment. 1
Initial Evaluation
Clinical Assessment
- Focus on pattern of symptom onset (acute, subacute, or chronic)
- Document distribution of sensory disturbances, motor deficits, and autonomic dysfunction
- Identify neurological level(s)
- Assess for associated symptoms (visual disturbances, fever, rash, etc.)
Imaging Beyond Initial MRI
- Repeat contrast-enhanced MRI of the spine after 2-7 days if initial MRI is normal but clinical suspicion remains high 1
- Consider MRI with thin slices and dedicated sequences to detect subtle lesions
- Brain MRI with contrast to evaluate for demyelinating diseases like MS or NMO 1
- MRI with flexion/extension views if positional myelopathy is suspected 1
Laboratory Investigations
Cerebrospinal Fluid Analysis
- Complete CSF analysis including:
- Cell count and differential (lymphomonocytic pleocytosis may indicate inflammation)
- Protein and glucose levels
- Oligoclonal bands (negative in MOG-associated disease, often positive in MS) 1
- IgG index and synthesis rate
- Cytology (to rule out malignancy)
- Microbiological studies (cultures, PCR for viral pathogens)
Serum Biomarkers
- Aquaporin-4 (AQP4) antibodies for neuromyelitis optica spectrum disorders 1
- Myelin oligodendrocyte glycoprotein (MOG) antibodies using cell-based assays 1
- Autoimmune panel (ANA, ENA, ANCA, anti-dsDNA, anti-Ro/La)
- Paraneoplastic antibodies panel (anti-Hu, anti-Yo, anti-Ri, etc.) 1
- Infectious disease markers:
- HIV, HTLV-1/2, syphilis serology
- Lyme disease
- Tuberculosis testing (QuantiFERON-TB Gold)
Metabolic and Nutritional Testing
- Vitamin B12 and methylmalonic acid levels
- Copper levels and ceruloplasmin
- Vitamin E levels
- Folate levels
Neurophysiological Studies
- Somatosensory evoked potentials (SSEPs) to detect subclinical spinal cord dysfunction 2
- Motor evoked potentials (MEPs) to assess corticospinal tract integrity
- Nerve conduction studies to differentiate peripheral from central processes
Advanced Imaging
- CT myelography if MRI is contraindicated or to evaluate for CSF flow abnormalities 1
- Spinal angiography if vascular malformation is suspected despite normal MRI 1
Special Considerations
Demyelinating Disorders
- Consider MOG-IgG testing in patients with:
- Bilateral optic neuritis with normal brain MRI
- Steroid-responsive and steroid-dependent symptoms
- ADEM-like presentation with brainstem involvement
- Recurrent myelitis episodes with normal or non-MS-typical brain lesions 1
Infectious Myelitis
- Viral PCR panel in CSF (HSV, VZV, EBV, CMV, enterovirus)
- Consider empiric antimicrobial therapy while awaiting results if infection is strongly suspected 3
Vascular Causes
- Consider spinal cord ischemia in patients with acute onset and risk factors for vascular disease
- Diffusion-weighted MRI sequences may show early changes in ischemia 1
Common Pitfalls to Avoid
- Not repeating MRI: Initial MRI may be normal in up to 10% of myelitis cases; consider repeat imaging after a few days 4
- Overlooking seronegative autoimmune myelitis: Not all autoimmune myelitis cases have detectable antibodies
- Missing metabolic causes: Vitamin B12 deficiency can cause myelopathy with normal initial MRI 1
- Neglecting paraneoplastic etiologies: Consider occult malignancy in patients >40 years with unexplained myelitis 1
- Incomplete CSF analysis: CSF findings may be the only abnormality in some myelitis cases 4
Follow-up
- Close clinical monitoring for symptom evolution
- Repeat imaging if symptoms progress or change
- Consider empiric treatment with corticosteroids if autoimmune/inflammatory etiology is suspected while awaiting test results
By following this systematic approach, clinicians can identify the underlying cause of myelitis symptoms even when initial spine MRI is normal, leading to appropriate treatment and improved patient outcomes.