Causes of Transverse Myelitis
Transverse myelitis is primarily caused by inflammatory processes that can be categorized into demyelinating diseases, systemic autoimmune disorders, infectious/parainfectious conditions, and other etiologies including drug/toxin-induced cases and paraneoplastic syndromes. 1
Major Etiological Categories
Demyelinating Diseases
- Multiple sclerosis (MS)
- Neuromyelitis optica (NMO) spectrum disorders
- MOG antibody-associated disorders
- Acute disseminated encephalomyelitis (ADEM)
Systemic Autoimmune Disorders
- Systemic lupus erythematosus
- Sjögren's syndrome
- Mixed connective tissue disorder
- Behçet disease
- Sarcoidosis
- Antiphospholipid antibody syndrome
Infectious/Parainfectious Causes
- Viral infections:
- HIV
- Cytomegalovirus
- Epstein-Barr virus
- Zika virus
- Chikungunya virus
- West Nile virus
- HTLV-1
- Bacterial infections:
- Syphilis
- Lyme disease
- Post-infectious immune response (occurring after resolution of infection)
Other Causes
- Immune checkpoint inhibitor therapy
- Paraneoplastic syndromes
- Drug/toxin-induced cases
- Vascular causes (spinal cord ischemia, arteriovenous malformations)
- Idiopathic (when no specific cause can be identified)
Diagnostic Considerations
When evaluating transverse myelitis, it's crucial to distinguish between idiopathic and secondary forms:
Idiopathic transverse myelitis: Diagnosed after excluding all other potential causes 2
Disease-associated transverse myelitis: Connected to underlying conditions like those listed above
Special diagnostic considerations:
- Longitudinally extensive transverse myelitis (lesions extending over ≥3 vertebral segments) strongly suggests neuromyelitis optica 1
- Monophasic demyelinating diseases like ADEM and postviral Devic's syndrome present special diagnostic challenges 3
- Some recurrent demyelinating diseases like neuromyelitis optica and recurrent longitudinally extensive transverse myelitis may be considered separate from MS by some clinicians 3
Diagnostic Approach
The diagnostic workup should include:
- MRI of the spine with and without contrast: Gold standard for evaluation, looking for T2 hyperintense lesions 1
- Cerebrospinal fluid analysis: Cell count, protein, glucose, oligoclonal bands, viral PCRs, cytology, and onconeural antibodies 1
- Blood tests: B12, HIV, RPR, ANA, Ro/La antibodies, TSH, aquaporin-4 IgG, and MOG antibodies 1
- Additional testing based on clinical suspicion: For vascular causes, paraneoplastic syndromes, or specific infections
Clinical Implications
Understanding the cause of transverse myelitis is critical for:
- Treatment decisions: Different etiologies require different therapeutic approaches
- Prognosis determination: The underlying cause significantly impacts recovery potential
- Relapse risk assessment: Some causes (like MS or NMO) have high relapse rates requiring long-term immunosuppression
Pitfalls to Avoid
- Don't assume all cases of transverse myelitis are idiopathic without thorough investigation
- Don't overlook subtle signs of systemic autoimmune diseases
- Don't miss testing for aquaporin-4 and MOG antibodies, as these identify specific treatable conditions
- Don't delay treatment while awaiting complete diagnostic workup in acute presentations
By systematically evaluating patients with transverse myelitis and identifying the underlying cause, clinicians can implement appropriate treatment strategies to improve outcomes and reduce the risk of permanent disability.