Research Article| Volume 441, 120385, October 15, 2022

Clinical use of CSF neopterin levels in CNS demyelinating diseases

Published:August 18, 2022DOI:


      • This study evaluated CSF neopterin in patients with CNS demyelinating diseases.
      • CSF neopterin levels were significantly higher in AQP4-IgG-positive NMOSD than MS.
      • CSF neopterin levels tended to be higher in MOGAD compared with MS.
      • CSF neopterin accurately discriminated active and inactive phases of the disease.



      There is some phenotypic overlap between MS, AQP4-IgG positive NMOSD, and MOG-IgG associated disease (MOGAD), and distinguishing a true relapse and a pseudorelapse can be difficult. CSF neopterin, a marker of inflammation-immune-mediated processes in the CNS, may be a useful marker in a wide range of CNS infectious and inflammatory diseases. We compared CSF neopterin levels and other CSF parameters in patients with MS, AQP4-IgG-positive NMOSD, and MOGAD and also investigated whether CSF neopterin levels can distinguish between active and inactive phases of the diseases.


      We retrospectively reviewed the medical records of 22 patients with MS, 18 with AQP4-IgG-positive NMOSD, and five with MOGAD. CSF neopterin concentrations were measured by HPLC with fluorometric detection.


      CSF neopterin levels at diagnosis were significantly higher in patients with AQP4-IgG-positive NMOSD (52.77 ± 34.56 pmol/mL) than patients with MS (16.92 ± 5.03 pmol/mL, p < 0.001), and tended to be higher in patients with MOGAD (28.87 ± 9.66 pmol/mL) than patients with MS (p = 0.092). ROC analysis revealed that CSF neopterin most accurately discriminated between MS and AQP4-IgG-positive NMOSD (AUC, 0.912; sensitivity, 75.0%; specificity, 100.0%). At diagnosis/relapse and during remission, CSF neopterin most accurately discriminated between the disease phases in patients with MS (AUC, 0.779; sensitivity, 58.1%; specificity, 94.7%) and patients with AQP4-IgG-positive NMOSD (AUC, 0.934; sensitivity, 83.3%; specificity, 94.1%).


      Measurement of CSF neopterin may be useful for differential diagnosis and assessment of disease activity in CNS demyelinating diseases. Further studies with larger cohorts, including comparisons with other biomarkers, are needed to validate the utility of CSF neopterin.



      AQP4 (aquaporin-4), CNS (central nervous system), CSF (cerebrospinal fluid), HPLC (high-performance liquid chromatography), MOG (myelin oligodendrocyte glycoprotein), MS (multiple sclerosis), NMOSD (neuromyelitis optica spectrum disorder), ROC (receiver operating characteristic.)
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