What are the causes of transverse myelitis?

Causes of Transverse Myelitis

Transverse myelitis has multiple etiologies including demyelinating disorders, autoimmune conditions, infections, medications, and paraneoplastic syndromes, with approximately one-third of cases remaining idiopathic despite extensive workup. 1, 2

Major Causes of Transverse Myelitis

Demyelinating Disorders

• Multiple Sclerosis (MS): Most common demyelinating cause, with spinal cord involvement in 80-90% of patients, typically affecting the cervical cord 1
• Neuromyelitis Optica (NMO): Characterized by lesions extending over 3 vertebral segments, associated with aquaporin-4 antibodies 1, 3
• MOG Antibody-Associated Disorder: Recently recognized entity with distinct clinical and radiological features 1
• Acute Disseminated Encephalomyelitis (ADEM): Typically monophasic condition with spinal cord involvement in approximately 25% of cases 1

Systemic Autoimmune Disorders

• Systemic Lupus Erythematosus: Can cause transverse myelitis, often requiring aggressive immunosuppression 1, 4
• Antiphospholipid Antibody Syndrome: Associated with poorer prognosis when present 1
• Sjögren's Syndrome: Can present with myelopathy 3
• Sarcoidosis: Granulomatous inflammation affecting the spinal cord 3

Infectious and Parainfectious Causes

• Viral infections: Including herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, HIV, HTLV-1 5
• Bacterial infections: Including mycoplasma pneumoniae, which can cause myelitis coincident with pneumonia 5
• Post-infectious: Occurring after resolution of infection as an immune-mediated phenomenon 6, 5

Medication/Treatment-Related

• Anticancer therapies: Including intrathecal methotrexate, cytarabine, cisplatin, carmustine, and thiotepa 4
• Immune checkpoint inhibitors: Can cause immune-related transverse myelitis requiring permanent discontinuation of the medication 1

Other Causes

• Paraneoplastic syndromes: Associated with underlying malignancies 2, 4
• Vitamin B12 deficiency: Causing subacute combined degeneration of the spinal cord 1
• Vascular disorders: Including spinal arteriovenous malformations and arteritis, more common in older patients 5
• Post-vaccination: Rare complication following various vaccinations 5

Diagnostic Approach

Imaging

• MRI spine with and without contrast is the gold standard, looking for:
  • T2 hyperintense lesions
  • Lesion length (>3 vertebral segments suggests NMO)
  • Enhancement pattern
  • Distribution (central vs. peripheral) 1, 7

Laboratory Testing

• CSF analysis: Look for pleocytosis, elevated protein, oligoclonal bands 1
• Serology: AQP4 antibodies (NMO), MOG antibodies, autoimmune panels, vitamin B12 levels 1, 3
• Infectious workup: PCR for viral pathogens (HSV, VZV, enterovirus), serology for mycoplasma, Lyme disease 5

Prognostic Considerations

The long-term outcome typically follows a "rule of thirds" 1:

• One-third recover with minimal or no sequelae
• One-third develop moderate permanent disability
• One-third suffer severe disability

Poor prognostic factors include:

• Extensive lesions on MRI
• Reduced muscle strength or sphincter dysfunction at onset
• Positive antiphospholipid antibodies
• Delayed treatment initiation (>2 weeks) 1

Clinical Pearls

• Idiopathic transverse myelitis should be a diagnosis of exclusion after thorough evaluation for secondary causes 5
• Careful distinction between various causes is crucial as treatment approaches differ significantly 3
• Rapid diagnosis and treatment initiation is essential to improve outcomes 1
• In patients with suspected demyelinating disease, careful follow-up is necessary as isolated transverse myelitis may be the first presentation of MS or NMO 4, 3