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Granulocyte activation markers are reliable biomarkers for distinguishing between multiple sclerosis and neuromyelitis optica spectrum disorder. Granulocyte activation markers are associated with the extent of neurological damage, indicating their potential role in the pathogenesis and treatment of acute neuromyelitis optica spectrum disorder. 

There are overlapping imaging and clinical characteristics in the clinical presentation of relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD), which hinder prompt diagnosis and administration of treatment. One of the differentiating pathogenic features in RRMS and NMOSD is granulocyte invasion into the brain. 

The current study quantified the levels of five granulocyte activation markers (GAM) in the cerebrospinal fluid (CSF) in patient cohorts of NMOSD and RRMS. The study concluded that GAMs are reliable for distinguishing between NMOSD and RRMS and are associated with the magnitude of neurological damage. The study findings are published in the Journal of Neurology, Neurosurgery, and Psychiatry. 

Patient Characteristics at Baseline

Compared to RRMS patients in both cohorts, NMOSD patients exhibited higher Expanded Disability Status Scale (EDSS) scores and were older. The proportion of CSF samples was relatively small in the RRMS patients compared to NMOSD patients in the discovery (37.5% vs. 76.2%, respectively) and validation cohorts (8.7% vs. 48.0%, respectively).

Expression Profiles of Biomarkers in NMOSD and RRMS Patients

The levels of GAM were found to be higher in NMOSD patients compared to RRMS patients in the discovery cohort. The independent validation cohort confirmed the GAM findings in NMOSD and RRMS patients. The levels of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were significantly higher in the subacute/chronic (s/c) RRMS patients.

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Effect of Immunomodulatory and Corticosteroid Therapy on Biomarker Levels

Patients with s/c NMOSD and acute NMOSD subjected to corticosteroid therapy demonstrated lower levels of GAM. Following the exclusion of patients undergoing corticosteroid therapy, it was confirmed that the levels of adhesion molecules and GAM were higher in NMOSD patients compared to RRMS patients.

Relationship Between Biomarker Levels and Disease Parameters

The levels of GAM in the CSF of NMOSD patients were associated with the EDSS scores. However, the levels of glial fibrillary acidic protein (GFAP) in the discovery cohort were not associated with EDSS scores in acute RRMS and NMOSD patients. Peak GAM levels were observed during NMOSD attacks, whereas the GAM levels were low and stable in MS. This can allow the differentiation between NMOSD and RRMS for ≤ 21 days from clinical exacerbation.

The study concluded that GAM composites are effective biomarkers for distinguishing MS and NMOSD. The pathogenic role of GAM in neurological impairment suggests the potential treatment target in acute NMOSD.


Leppert, D., Watanabe, M., Schaedelin, S., Piehl, F., Furlan, R., Gastaldi, M., Lambert, J., Evertsson, B., Fink, K., Matsushita, T., Masaki, K., Isobe, N., Kira, J. I., Benkert, P., Maceski, A., Willemse, E. A., Oechtering, J., Orleth, A., Meier, S., & Kuhle, J. (2023). Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, jnnp-330796. https://doi.org/10.1136/jnnp-2022-330796