What are the guidelines for managing transverse myelitis?

Management of Transverse Myelitis

Immediate Actions

Permanently discontinue any immune checkpoint inhibitors immediately if the patient is receiving them, and initiate high-dose intravenous methylprednisolone 1g daily for 3-5 days as first-line treatment. 1, 2, 3

For moderate to severe cases with significant weakness, sensory changes, or sphincter dysfunction, strongly consider adding IVIG 2g/kg over 5 days (0.4g/kg/day) concurrently with pulse corticosteroids. 1, 2, 3

Diagnostic Workup

Obtain urgent neurology consultation to guide phenotype determination and management. 1, 2, 4

Essential imaging and laboratory studies:

• MRI spine with and without contrast using thin axial cuts through the suspected abnormality region, looking for T2-weighted hyperintense lesions that may appear wedge-shaped on axial views and cigar-shaped on sagittal views 1, 2, 4
• MRI brain with and without contrast to evaluate for demyelinating disorders 1
• Lumbar puncture: cell count with differential, protein, glucose, oligoclonal bands, viral PCRs (especially HSV and JCV), cytology to exclude leptomeningeal metastases, and onconeural antibodies 1, 2, 4
• Blood tests: B12, HIV, RPR, ANA, Ro/La, TSH, aquaporin-4 IgG (for neuromyelitis optica spectrum disorder), MOG-IgG antibodies, antiphospholipid antibodies, paraneoplastic panel 1, 2, 3
• Evaluate for urinary retention and constipation as these autonomic manifestations are common 1, 2, 4

Treatment Algorithm by Severity

Grade 1 (Mild): Asymptomatic or minimal symptoms

• Hold immune checkpoint inhibitors if applicable and monitor closely 1
• Consider observation versus initiating prednisone 0.5-1 mg/kg/day if symptoms progress 1

Grade 2 (Moderate): Some interference with activities, concerning symptoms but no severe weakness

• Hold immune checkpoint inhibitors permanently 1
• Initiate methylprednisolone 1-2 mg/kg/day IV 1
• Consider escalation to pulse dosing if symptoms worsen 1

Grade 3-4 (Severe): Limiting self-care, severe weakness, respiratory compromise, or sphincter dysfunction

• Admit patient immediately 1
• Permanently discontinue immune checkpoint inhibitors 1
• Administer methylprednisolone 1g IV daily for 3-5 days (pulse dosing) 1, 2, 3
• Strongly consider IVIG 2g/kg over 5 days concurrently 1, 2, 3
• Consider plasmapheresis if no improvement or symptoms worsen after 3 days of pulse steroids and IVIG 1, 2, 3
• Taper steroids following acute management over at least 4-6 weeks 1, 2

Special Clinical Scenarios

SLE-Associated Transverse Myelitis

Combine intravenous methylprednisolone with intravenous cyclophosphamide if used promptly within the first few hours, as neurological response paralleled by MRI improvement occurs within days to 3 weeks. 1, 5 This combination has shown superior outcomes compared to corticosteroids alone, with most patients achieving ability to walk and partial or total sphincter control. 5

Antiphospholipid Antibody-Positive Myelopathy

Add anticoagulation therapy in addition to immunosuppressive treatment, particularly in patients not responding to immunosuppression alone. 1, 2

Neuromyelitis Optica Spectrum Disorder (NMOSD)

If aquaporin-4 IgG positive or longitudinally extensive transverse myelitis (≥3 vertebral segments), more aggressive immunosuppression is required. 2, 3, 4 Consider rituximab if positive for autoimmune encephalopathy antibodies or limited improvement with standard therapy. 1, 2, 3

Second-Line and Refractory Treatment

If no improvement after 3-5 days of pulse corticosteroids and IVIG, or if symptoms worsen:

• Plasmapheresis is the preferred second-line option 1, 2, 3
• Rituximab may be beneficial in autoimmune-positive cases or inadequate response to other therapies 1, 2, 3
• Note: Plasmapheresis immediately after IVIG will remove immunoglobulin, so timing matters 1

Maintenance Therapy

Maintenance immunosuppressive therapy is essential as relapses occur in 50-60% of cases during corticosteroid dose reduction. 1, 2 Options include:

• Azathioprine 2
• Mycophenolate mofetil 1
• Methotrexate 1
• Continued rituximab for NMOSD-associated cases 2

Prognostic Factors and Timing

Poor prognostic indicators:

• Extensive spinal cord MRI lesions, especially longitudinally extensive transverse myelitis affecting ≥3 vertebral segments 2, 3, 4
• Reduced muscle strength or sphincter dysfunction at presentation 1, 2, 3
• Delay >2 weeks in initiating therapy 1, 2, 3

The evidence strongly supports early aggressive treatment. A pediatric study showed that high-dose methylprednisolone reduced median time to walk independently from 97 to 23 days and increased full recovery rate from 10% to 80% within 12 months. 6

Critical Clinical Pearls

Transverse myelitis causes spastic paralysis with increased deep tendon reflexes (upper motor neuron signs), distinguishing it from Guillain-Barré syndrome which presents with flaccid paralysis and reduced/absent reflexes. 4 This distinction is crucial for diagnosis.

CSF analysis typically reveals lymphocytic pleocytosis and elevated protein, but normal glucose and negative cytology (to exclude leptomeningeal metastases). 1

At peak deficit, approximately 50% of patients are completely paraplegic, virtually all have bladder dysfunction, and 80-94% have sensory abnormalities. 7 Natural history shows roughly one-third each recover fully, have moderate disability, or have severe permanent disability. 7

Do not delay treatment waiting for complete diagnostic workup—initiate pulse methylprednisolone once infection and malignancy are reasonably excluded. 1, 2 The window for optimal treatment response is narrow, and delays beyond 2 weeks significantly worsen outcomes. 1, 2, 3