What is the diagnostic approach for a patient with suspected transverse myelitis, considering their clinical presentation, medical history, and potential underlying conditions such as multiple sclerosis, infections, or autoimmune disorders?

Diagnostic Approach for Transverse Myelitis

The diagnosis of transverse myelitis requires urgent spinal MRI with contrast to exclude compressive lesions, followed by CSF analysis demonstrating inflammation, and systematic evaluation to distinguish between idiopathic disease versus secondary causes including multiple sclerosis, neuromyelitis optica spectrum disorder, MOG-associated disease, infections, and systemic autoimmune conditions. 1, 2, 3

Immediate Diagnostic Priorities

Step 1: Exclude Compressive Myelopathy (Emergency)

• Obtain urgent spinal MRI with gadolinium contrast within hours of presentation, as compressive myelopathy from tumor, abscess, or herniated disc is clinically indistinguishable from transverse myelitis and requires emergent surgical intervention 1, 2, 3
• Include whole spinal cord imaging, not just the symptomatic level, as lesions may be multifocal 4

Step 2: Confirm Inflammatory Process

• Perform lumbar puncture if MRI shows no compression, looking for:
  • Pleocytosis (elevated white blood cells, typically lymphocytic with <50 cells/mm³) 5, 1
  • Elevated protein indicating blood-CSF barrier disruption 6
  • Oligoclonal bands (OCBs) specific to CSF that differ from serum bands 5, 4
  • Elevated IgG index 5, 4
• Normal CSF does not exclude transverse myelitis but should prompt reconsideration of alternative diagnoses 1, 2

Critical MRI Pattern Recognition

Lesion Characteristics That Guide Diagnosis

• Longitudinally extensive transverse myelitis (LETM) spanning ≥3 contiguous vertebral segments strongly suggests neuromyelitis optica spectrum disorder (NMOSD) or MOG-associated disease, not typical multiple sclerosis 5, 7
• Short segment lesions (<3 vertebral segments) are more consistent with MS-associated myelitis 5, 7
• Central cord involvement with T1 hypointensity suggests more severe tissue damage and worse prognosis 6, 2
• Lumbar cord lesions associate with worse outcomes and should prompt consideration of conus involvement 5, 6

Brain MRI Is Mandatory

• Obtain brain MRI with contrast in all patients to assess for dissemination in space, which distinguishes MS from isolated transverse myelitis 5, 4, 2
• Look for MS-specific patterns: periventricular lesions (≥3), juxtacortical lesions, infratentorial lesions, or Dawson's finger-type lesions 5, 4
• Absence of typical MS brain lesions in the setting of LETM increases suspicion for NMOSD or MOG-associated disease 5

Essential Serological Testing

Antibody Panel to Distinguish Demyelinating Subtypes

• Aquaporin-4 IgG (AQP4-IgG) antibody testing is mandatory using cell-based assays, as this distinguishes NMOSD from MS—critical because MS treatments can worsen NMOSD 5, 7, 8
• MOG-IgG antibody testing using cell-based assays (not ELISA or Western blot, which are obsolete) should be performed on serum, as MOG-associated disease presents with LETM, often OCB-negative, and may worsen with interferon-beta 5
• Test serum, not CSF, for both AQP4-IgG and MOG-IgG, as these antibodies are produced extrathecally 5

Infectious and Systemic Workup

• Infectious serologies based on clinical context: HIV, HTLV-1, Lyme disease, syphilis, herpes viruses (HSV, VZV, EBV, CMV), enterovirus 7, 1, 2, 3
• Autoimmune panel: ANA, anti-dsDNA, antiphospholipid antibodies, SSA/SSB for lupus and Sjögren's syndrome 7, 2
• Sarcoidosis evaluation: ACE level, chest imaging if systemic symptoms present 7
• Paraneoplastic antibodies (anti-Hu, anti-Yo, anti-amphiphysin) if age >50 or constitutional symptoms suggest malignancy 7, 2

Distinguishing MS from Isolated Transverse Myelitis

MS Diagnosis Requires Dissemination in Time and Space

• Two or more clinical attacks with objective evidence of two or more lesions fulfills MS criteria without additional testing 5, 4
• One attack with evidence of one lesion (typical presentation of transverse myelitis) requires:
  • MRI evidence of dissemination in space: ≥3 of 4 criteria (≥1 gadolinium-enhancing or ≥9 T2 lesions, ≥1 infratentorial lesion, ≥1 juxtacortical lesion, ≥3 periventricular lesions) 5, 4
  • MRI evidence of dissemination in time: new T2 lesion or gadolinium-enhancing lesion on follow-up scan ≥3 months after initial event, or simultaneous enhancing and non-enhancing lesions 5, 4
• Positive CSF (OCBs or elevated IgG index) plus ≥2 brain lesions can substitute for full MRI dissemination in space criteria 5, 4

Red Flags Against MS Diagnosis

• Ascending sensory disturbance or weakness is atypical for MS and suggests Guillain-Barré syndrome, NMOSD, or other myelopathies 8
• Severe sphincter dysfunction early in course, especially with conus involvement, suggests MOG-associated disease or NMOSD 5
• Steroid-dependent relapses or worsening after interferon-beta treatment suggests MOG-associated disease 5
• Absence of oligoclonal bands in the setting of LETM strongly favors NMOSD or MOG-associated disease over MS 5

Clinical Features That Predict Prognosis

Poor Prognostic Indicators

• Older age at onset independently predicts worse disability outcomes 6
• Complete transverse myelitis (bilateral motor, sensory, and sphincter involvement) has 10.8-fold increased odds of severe disability compared to partial myelitis 6
• Overt or subclinical peripheral nervous system involvement (detected by nerve conduction studies) has 9.4-fold increased odds of severe disability 6
• Infectious antecedents (post-infectious myelitis) associate with worse long-term outcomes 6
• Lumbar cord lesions predict worse functional recovery 6
• Blood-CSF barrier damage (elevated CSF protein) correlates with poor outcomes 6

Additional Diagnostic Studies to Consider

• Nerve conduction studies and EMG should be performed if there is any suspicion of peripheral nervous system involvement, as this significantly worsens prognosis and may indicate concurrent Guillain-Barré syndrome 6
• Visual evoked potentials can provide objective evidence of subclinical optic nerve involvement, supporting MS diagnosis or suggesting NMOSD/MOG-associated disease 5, 4

Diagnostic Algorithm Summary

1. Emergency spinal MRI with contrast → exclude compression 1, 2
2. If no compression: lumbar puncture → confirm inflammation 1, 3
3. Brain MRI with contrast → assess for MS dissemination in space 5, 4
4. Serum AQP4-IgG and MOG-IgG (cell-based assays) → distinguish demyelinating subtypes 5
5. Infectious/autoimmune serologies based on clinical context 7, 2
6. Nerve conduction studies if any peripheral signs or poor recovery 6
7. Follow-up MRI at 3 months if MS suspected but dissemination in time not yet demonstrated 5, 4

Critical Pitfalls to Avoid

• Never diagnose MS based solely on white matter lesions—the clinical syndrome must be typical of demyelination, and alternative diagnoses must be excluded 8
• Never start MS disease-modifying therapy without excluding NMOSD and MOG-associated disease, as interferon-beta and natalizumab can worsen these conditions 5, 8
• Never assume normal MRI excludes transverse myelitis—early imaging may be negative, and repeat MRI or clinical follow-up is essential 2
• Never overlook compressive lesions—surgical emergencies must be identified immediately 1, 2
• Never ignore atypical features such as ascending weakness, severe sphincter dysfunction, or absence of brain lesions, as these suggest diagnoses other than MS 5, 8