CSF Myeloid Microvesicles May Be Biomarkers of MS Neuroinflammation, Disease Course

Conceptual image of a multiple sclerosis neuron.
Study researchers evaluated the diagnostic and prognostic value of myeloid microvesicles as multiple sclerosis biomarkers in the clinical setting.

Myeloid microvesicles in cerebrospinal fluid (CSF) were useful in distinguishing relapsing-remitting multiple sclerosis (MS) and predicting future disease activity and disability in study published in the Annals of Neurology.

The study included 601 patients who underwent lumbar puncture during diagnostic work-up for suspected neurological disease. These patients were discharged with a diagnosis of either a neuroinflammatory (n=298) or neurodegenerative disease/dementia (n=274) or no neurological disease (n=29). Study researchers measured the concentration of myeloid microvesicles in CSF samples using flow-cytometry.

A total of 21 patients in the neuroinflammatory disease group had radiologically isolated syndrome (RIS), 50 had clinically isolated syndrome (CIS), 159 had relapsing/remitting MS (RRMS), 33 had progressive MS (PMS), 7 had autoimmune encephalitis, 19 had idiopathic central nervous system neuroinflammatory disease, and 9 had recurrent myelitis. Patients with RRMS had a significantly higher prevalence of disease activity on magnetic resonance imaging compared with the group of patients with CIS, RIS, and PMS (P <.001).

Patients with neuroinflammatory diseases had significantly elevated CSF myeloid microvesicles relative to the neurodegenerative (median, 1615/ml vs 325/ml, respectively; P <.0001) and relative to controls (median 1615/ml vs 270/ml; P <.0001) groups.

Pairwise comparisons demonstrated significantly higher concentrations of microvesicles among patients with MS compared with those with autoimmune encephalitis (P =.03). The study researchers also found significantly higher CSF myeloid microvesicles in patients with RRMS compared with those with CIS (P =.002) and PMS (P =.005).

Additionally, the group of patients with active disease had significantly higher median CSF myeloid microvesicles concentrations (3185/ml) compared with the nonactive group of patients (1340/ml; P <.0001).

Patients with RRMS who had a relapse in the previous 30 days had significantly higher levels of CSF myeloid microvesicles compared with patients without recent disease activity (median, 3740/ml vs 1370/ml, respectively; P =.0137).

Levels of CSF microvesicles were able to significantly discriminate between the RRMS and control groups (area under the curve [AUC], 0.939; 95% CI, 0.94-0.974; P <.0001), as well as between RIS and unspecific brain lesions (AUC, 0.942; 95% CI, 0.865-1.0; P <.0001).

Microvesicles were also found to be independent predictors of disease prognosis in patients with RRMS and PMS. Specifically, microvesicles independently predicted disease activity for RRMS (hazard ratio [HR], 1.967; 95% CI, 1.147-3.372) and disability accrual for PMS (HR, 10.767; 95% CI, 1.335-86.812).

A potential limitation of this study was the use of different diagnostic criteria across patients, which could have biased the results for the prognostic assessments in patients with RRMS. The study’s partial retrospective design as well as the small sample size represented additional limitations.

In conclusion, the researchers wrote the “results confirm that CSF myeloid microvesicles are a clinically meaningful biomarker of neuroinflammation and microglial/macrophage activity in vivo.”

Disclosure: This clinical trial was supported by Merck.


Gelibter S, Pisa M, Croese T, et al. Spinal fluid myeloid microvesicles predict disease course in multiple sclerosis. Ann Neurol. 2021;90(2):253-265. doi:10.1002/ana.26154