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Medically reviewed by Dr. Shani Saks, D.O. on Sept. 3, 2023

A recent study reveals the potential of granulocyte activation markers in cerebrospinal fluid as a reliable biomarker for distinguishing neuromyelitis optica spectrum disorder from multiple sclerosis, even when the gold-standard diagnostic biomarker, anti-aquaporin-4 protein antibodies, is negative.

  • Granulocyte activation marker levels in cerebrospinal fluid can differentiate neuromyelitis optica spectrum disorder from multiple sclerosis.
  • Granulocyte activation marker levels correlate with the severity of neurological impairment in acute neuromyelitis optica spectrum disorder.
  • The new findings could have significant implications for diagnostic procedures and treatment options.

Neuromyelitis optica spectrum disorder (NMOSD) often presents diagnostic challenges due to its clinical and MRI features being similar to those of multiple sclerosis (MS). Historically, around 20–40% of NMOSD patients test negative for the diagnostic biomarker anti-aquaporin-4 protein antibodies (aAQP4), making differentiation even more challenging. However, granulocyte invasion into brain lesions is a significant feature of NMOSD, suggesting that identifying granulocyte activation markers (GAM) could offer a solution.

The Use of Granulocyte Activation Markers in Diagnosis

According to a study published in the Journal of Neurology, Neurosurgery, and Psychiatry, researchers found that in acute NMOSD, GAM levels and adhesion molecules in the CSF were notably higher than in relapsing–remitting multiple sclerosis (RRMS). Notably, the researchers found that the more GAM and adhesion molecules were present, the worse the neurological symptoms seemed to be in acute NMOSD. In addition, a composite of GAM provided impressive specificity and sensitivity values, allowing researchers to differentiate between NMOSD and RRMS, even in patients who tested negative for aAQP4.

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Granulocyte Activation Marker Levels Reflect Neurological Impairment

The results of this study also revealed a connection between GAM levels and the severity of NMOSD exacerbation, noting that GAMs aren’t just diagnostic markers; they mirror the clinical state of the patient. Moreover, these findings provide insights into the pathology of NMOSD, highlighting the role of granulocytes in neural tissue damage and the development of disability in the disease.

How Granulocyte Activation Markers Could Impact Clinical Practice

For healthcare providers, these findings offer a promising direction in diagnosing NMOSD, especially in the acute stages when quick therapeutic decisions can be vital. Given that GAM levels can reflect the severity of NMOSD, they can be used as a real-time indicator of disease activity. Additionally, GAMs may be a potential novel therapeutic target for NMOSD, suggesting new pathways for treatment in the acute stages of the disorder.


Leppert, D., Watanabe, M., Schaedelin, S., Piehl, F., Furlan, R., Gastaldi, M., Lambert, J. J., Evertsson, B., Fink, K., Matsushita, T., Kitajima, M., Isobe, N., Kira, J., 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, 94(9), 726–737. https://doi.org/10.1136/jnnp-2022-330796