What is the appropriate treatment for a patient with Longitudinally Extensive Transverse Myelitis (LETM) presenting with markedly elevated cerebrospinal fluid (CSF) protein and cell count?

Treatment Approach for LETM with Markedly Elevated CSF Protein and Cell Count

This patient requires urgent exclusion of infectious and malignant etiologies before initiating immunotherapy, given the extremely elevated CSF protein (1000 mg/dL) and pleocytosis (150 cells), which are atypical for standard demyelinating disease and suggest either severe inflammatory demyelination, infection, or leptomeningeal pathology.

Immediate Diagnostic Priorities

Rule Out Critical Mimics First

The CSF profile described is highly unusual for typical inflammatory LETM and mandates urgent investigation:

• CSF protein of 1000 mg/dL is 10-20 times the upper limit of normal and far exceeds what is typically seen in demyelinating disease 1
• Cell count of 150 is markedly elevated compared to typical viral encephalitis (tens to hundreds) or standard demyelinating conditions 1
• This profile raises concern for leptomeningeal metastasis, tuberculous meningitis, or severe infectious myelitis rather than primary inflammatory demyelination 1

Essential Immediate Workup

CSF studies must include 1:

• Cytology for malignant cells (minimum 5-10 mL, processed within 30 minutes) - leptomeningeal metastasis can present with LETM-like imaging 1
• Gram stain, bacterial cultures, and mycobacterial studies (6 mL for TB) 1
• Viral PCR panel including HSV-1/2, VZV, enterovirus 1
• CSF glucose with simultaneous plasma glucose - low CSF:plasma ratio suggests bacterial/TB infection 1
• Opening pressure - elevated in 21-42% of leptomeningeal disease 1

Serum antibody testing 1:

• AQP4-IgG and MOG-IgG using cell-based assays (serum is preferred specimen) 1
• These should be sent urgently but treatment should not await results if infection is excluded 1

Treatment Algorithm Based on Diagnostic Findings

If Infection and Malignancy Are Excluded

Initiate high-dose corticosteroids immediately 1, 2:

• IV methylprednisolone 1 gram daily for 3-5 days 1
• This is appropriate for severe inflammatory LETM regardless of antibody status 1, 2

Consider plasma exchange (PLEX) or IVIG if 1:

• Inadequate response to steroids within 5-7 days 1
• Steroid-dependent symptoms or flare-up after tapering (characteristic of MOG-EM) 1
• PLEX dosing: standard 5-7 exchanges over 10-14 days 1
• IVIG dosing: 2 g/kg over 5 days (0.4 g/kg/day) 1

Special Considerations for This CSF Profile

The markedly elevated protein suggests possible 3, 4:

• Blood-spinal cord barrier disruption - may indicate more severe inflammatory process 3
• Consider repeat CSF analysis in 24-48 hours if initial cytology negative but clinical suspicion for malignancy remains high 1

MOG-antibody disease is more likely if 1:

• CSF shows pleocytosis with neutrophils (up to 10% neutrophils described) 1
• Negative oligoclonal bands 1, 5
• Good initial steroid response but relapse on tapering 1

Critical Pitfalls to Avoid

• Do NOT delay empiric antimicrobial therapy (IV acyclovir, broad-spectrum antibiotics) until CSF results return if any concern for infection exists 1
• Do NOT assume this is standard demyelinating disease without excluding leptomeningeal metastasis - CSF cytology is mandatory 1
• Do NOT rely on a single negative CSF cytology - sensitivity increases to 80% with second optimized lumbar puncture 1
• Do NOT start immunosuppression before infection is excluded - this could be catastrophic if bacterial/TB meningitis is present 1

Long-Term Management Considerations

If MOG-IgG positive 1:

• Rituximab may be required for stabilization if recurrent attacks occur 1
• Steroid taper should be slow (over 4-6 weeks minimum) as MOG-EM is characteristically steroid-dependent 1

If AQP4-IgG positive 1:

• Requires long-term immunosuppression to prevent relapses
• Consider rituximab, azathioprine, or mycophenolate 1

If seronegative 4:

• Idiopathic seronegative LETM may have better prognosis than seropositive disease 4
• Male predominance, older age, and absence of recurrence are more common 4
• May not require long-term immunosuppression if monophasic course 4, 6