CSF myeloid microvesicles were useful in a study published in the Annals of Neurology to distinguish relapsing-remitting multiple sclerosis (MS) and to predict future disease activity and disability.
The study included 601 patients who had a lumbar puncture performed during the diagnostic work-up if a neurological disease was suspected. These patients were discharged with a diagnosis of neuroinflammatory (n = 298) or neurodegenerative disease / dementia (n = 274) or no neurological disease (n = 29). The 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 neuroinflammatory central nervous system disease, and 9 had recurrent myelitis. Patients with RRMS had a significantly higher prevalence of disease activity on magnetic resonance imaging compared to the group of patients with CIS, RIS, and PMS (P <0.001).
Patients with neuroinflammatory diseases had significantly increased myeloid microvesicles in the CSF compared to the neurodegenerative (median 1615 / ml or 325 / ml; P <0.0001) and relative to the controls (median 1615 / ml vs 270 / ml; P < 0.0001.). ) Groups.
Pair-wise comparisons showed significantly higher concentrations of microvesicles in patients with MS compared to patients with autoimmune encephalitis (P = .03). The study researchers also found significantly higher myeloid microvesicles in the CSF in patients with RRMS compared to patients with CIS (P = 0.002) and PMS (P = 0.005).
In addition, the patient group with active disease had significantly higher median concentrations of myeloid microvesicles in the CSF (3185 / ml) than the inactive patient group (1340 / ml; p <0.0001).
Patients with RRMS who had relapsed within the last 30 days had significantly higher levels of myeloid microvesicles in the CSF compared to patients with no recent disease activity (median 3740 / ml and 1370 / ml, respectively; P = 0.0137).
The concentrations of the CSF microvesicles could differ significantly between the RRMS and the control group (area under the curve [AUC], 0.939; 95% CI, 0.94-0.974; P <0.0001), as well as between RIS and unspecific brain lesions (AUC 0.942; 95% CI 0.865-1.0; P <0.0001).
Microvesicles were also shown to be independent predictors of disease prognosis in patients with RRMS and PMS. In particular, microvesicles independently predicted disease activity for RRMS (hazard ratio [HR], 1.967; 95% CI 1.147–3.372) and disability provision for PMS (HR, 10.767; 95% CI, 1.335–86.812).
A potential limitation of this study was the use of different diagnostic criteria in the patients, which may have skewed the results for the prognostic scores in patients with RRMS. The partially retrospective design of the study and the small sample size were additional restrictions.
In summary, the researchers wrote that “the results confirm that myeloid microvesicles in CSF are a clinically important biomarker for neuroinflammation and microglial / macrophage activity in vivo”.
Disclosure: This clinical study was supported by Merck.
S. Gelibter, M. Pisa, T. Croese et al. Myeloid microvesicles of the spinal fluid predict the course of the disease in multiple sclerosis. Ann Neurol. 2021; 90 (2): 253-265. doi: 10.1002 / ana.26154