What are the characteristic cerebrospinal fluid (CSF) findings in Neuromyelitis Optica Spectrum Disorder (NMOSD) patients with longitudinally extensive transverse myelitis (LETM)?

CSF Findings in LETM Specifically NMOSD

In NMOSD patients with LETM, CSF typically shows pleocytosis (present in ~50% of cases) with frequent neutrophilic predominance, elevated protein with blood-CSF barrier dysfunction, and notably absent or only transiently positive oligoclonal bands—features that distinguish it from multiple sclerosis. 1

Key CSF Characteristics in AQP4-Positive NMOSD with LETM

Cell Count and Pleocytosis

• Pleocytosis is present in approximately 50% of lumbar punctures, with a median white cell count of 19 cells/μl (range 6-380 cells/μl) 1
• Neutrophilic pleocytosis is characteristic, often accompanied by eosinophils, activated lymphocytes, and/or plasma cells—a pattern distinctly different from MS 1
• White cell counts >50/μl suggest MOG-EM or AQP4-NMOSD rather than MS 2
• The degree of pleocytosis correlates significantly with disease activity and the length of spinal cord lesions in acute myelitis 1

Oligoclonal Bands (OCBs)

• CSF-restricted oligoclonal IgG bands are absent in most AQP4-positive NMOSD patients—a critical distinguishing feature from MS 1
• When OCBs are present, intrathecal IgG synthesis is low, transient, and importantly restricted to acute relapses only 1
• This absence of OCBs is a key diagnostic feature: 87-88% of MOG-EM patients also lack oligoclonal bands 3

Protein and Blood-CSF Barrier Dysfunction

• Elevated total protein is common, reflecting blood-CSF barrier dysfunction 1
• Albumin CSF/serum ratios correlate significantly with disease activity and with the length of spinal cord lesions in patients with acute myelitis 1
• CSF L-lactate levels also correlate with disease activity and lesion length 1

AQP4 Antibodies in CSF

• CSF AQP4-IgG are present in patients with high serum titers and correlate with spinal MRI lesion length and CSF inflammatory parameters 4
• CSF AQP4-IgG titers are associated with clinical activity and neuroinflammation, with clinical improvement correlating with decreased CSF (but not serum) AQP4-IgG titers 4
• However, serum remains the specimen of choice for AQP4-IgG testing, as MOG-IgG is produced mostly extrathecally, resulting in lower CSF than serum titers 5

Clinical Context and Disease Activity

Acute vs. Remission Phase

• CSF findings differ significantly between acute myelitis and acute optic neuritis at the time of lumbar puncture 1
• Pleocytosis and blood-CSF barrier dysfunction may persist during remission in some patients, possibly indicating sustained subclinical disease activity 1

Correlation with Imaging

• The degree of CSF abnormalities (pleocytosis, protein elevation, albumin ratio) correlates significantly with the length of spinal cord lesions on MRI in acute myelitis 1

Diagnostic Algorithm for LETM

When evaluating a patient with LETM:

1. Immediately test for both AQP4-IgG and MOG-IgG antibodies in parallel if cost permits; if cost is prohibitive and disease is stable, test AQP4-IgG first as it is more frequent 2

2. Perform CSF analysis looking specifically for:

   • Neutrophilic pleocytosis or WCC >50/μl (suggests NMOSD or MOG-EM over MS) 2
   • Absence of oligoclonal bands (present in 87-88% of MOG-EM and most AQP4-NMOSD cases) 3, 1
   • Elevated protein and albumin ratio (correlates with lesion severity) 1

3. Key red flags that argue against MS and support NMOSD:

   • LETM affecting ≥3 vertebral segments 2, 6
   • Neutrophilic pleocytosis 1
   • Absence of CSF-restricted OCBs 1
   • Conus medullaris involvement 2

Important Caveats

• Normal CSF does not exclude NMOSD—approximately 50% of cases may have normal cell counts 1, 7
• AQP4-IgG testing is mandatory in all patients with unclear longitudinally extensive spinal cord lesions and should be performed preoperatively if biopsy is being considered 7
• Different detection methods should be used in doubtful cases due to heterogeneity of available assays 7
• CSF analysis should be performed under optimal conditions: obtain >10 mL (minimum 5 mL), process within 30 minutes, and avoid hemorrhagic contamination 5