CSF Protein Range in Longitudinally Extensive Transverse Myelitis (LETM)
CSF protein in LETM is typically mildly to moderately elevated, ranging from approximately 50-150 mg/dL, though normal values can occur, particularly in aquaporin-4 antibody-negative cases.
Protein Elevation Patterns by LETM Subtype
Aquaporin-4 Antibody-Positive LETM (Neuromyelitis Optica Spectrum)
- CSF protein is generally mildly elevated in the range of 50-120 mg/dL, consistent with the typical viral encephalitis pattern of mildly elevated protein with normal glucose 1
- The protein elevation reflects severe astrocytic damage, as evidenced by markedly elevated CSF glial fibrillary acidic protein (GFAP) levels reaching as high as 18,966.7 ng/ml during acute relapse (normal <1 ng/ml) 2
- CSF pleocytosis is common, with one case series documenting 90 white cells/μl with 5% neutrophils in a patient with simultaneous optic neuritis and LETM 1
- Oligoclonal bands are typically absent, distinguishing this from multiple sclerosis 1
Aquaporin-4 Antibody-Negative LETM
- CSF protein levels tend to be lower or normal compared to seropositive cases, reflecting the absence of significant astrocytic damage 3
- CSF GFAP levels are not increased in antibody-negative LETM, contrasting sharply with the marked elevation seen in seropositive disease 3
- These patients show milder clinical presentations overall with spinal cord confinement 3
Critical Diagnostic Considerations
Essential CSF Parameters Beyond Protein
- CSF glucose must be measured simultaneously with plasma glucose to calculate the CSF:plasma glucose ratio (normal >0.66), as absolute CSF glucose values alone are insufficient for interpretation 1, 4
- CSF cell count with differential is absolutely essential, as LETM typically shows lymphocytic pleocytosis (tens to hundreds of cells/μL) 1
- CSF lactate <2 mmol/L effectively rules out bacterial disease, which is a critical differential diagnosis 1, 5
Age-Dependent Reference Values
- Standard CSF protein upper reference limits of 45 mg/dL are outdated; data-driven URLs should be higher and stratified by age to improve diagnostic specificity 6
- Applying age-adjusted reference values increases specificity from 39% to 57-64% without compromising sensitivity 6
Pathophysiological Context
The protein elevation in LETM results from:
- Reduced CSF flow rate due to spinal cord inflammation and potential blockade, which increases protein concentration through both reduced volume exchange and increased molecular net flux without actual barrier permeability changes 7
- Blood-CSF barrier dysfunction that maintains constant molecular size-dependent selectivity even with pathologically elevated protein levels 7
- In AQP4-positive cases, severe astrocytic damage releases massive amounts of GFAP, which correlates temporally with clinical relapse and declines sharply after high-dose methylprednisolone therapy 2
Common Diagnostic Pitfalls
- Do not interpret mildly elevated protein as definitive evidence of bacterial meningitis; bacterial meningitis typically shows CSF protein >220 mg/dL (>2.2 g/L), while levels <60 mg/dL make bacterial disease very unlikely 4
- Correct for traumatic tap by subtracting 1 white cell for every 7000 red blood cells and 0.1 g/dL protein for every 100 red blood cells 1, 8
- Send CSF for MOG antibody testing in addition to AQP4 antibodies, as MOG-associated disease can present identically to LETM and requires different prognostic counseling 1, 3
- Recognize that approximately 5-10% of viral encephalomyelitis cases may have normal initial CSF findings, necessitating repeat lumbar puncture at 24-48 hours if clinical suspicion remains high 1, 5