Abstract
Objective: To evaluated the prognostic ability of several serum cytokines in clinically isolated syndrome (CIS) patients regarding second events and conversion to multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD).Methods: We enrolled 69 CIS patients whose serum samples were collected during the acute phase of the first onset before immunotherapy. Fifteen other non-inflammatory neurological disorder (OND) patients were also included. The serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13, IL-17A, IL-21, IL-23, interferon-γ (IFN-γ), and transforming growth factor beta 1 (TGF-β1) were measured using the human cytokine multiplex assay or ELISA. Patients were seen every 3–6 months. Unscheduled visits occur in case of exacerbations. Clinical measures of disease progression were recorded.Results: Twenty CIS cases had second events during follow-up at a mean time of 15.3 ± 9.9 months. Serum IL-10 levels were significantly lower in CIS patients who relapsed compared to patients who did not. Low serum IL-10 levels were associated with higher risk and shorter times to second events. In clinical correlations, a significantly higher CSF white blood cells count, number of T2 lesions, and gadolinium-enhancing (Gd+) lesions in baseline MRI were found in the low serum IL-10 level group. Of the 20 relapsed cases, seven converted to MS, and eight converted to NMOSD. No significant differences were found in any cytokine levels between these patients at first onset.Conclusions: These findings support using serum IL-10 as a biomarker associated with the risk of relapse and the time to second events in patients with CIS. However, serum cytokine levels can not differentiate between the conversion from CIS to MS or NMOSD.
Highlights
Idiopathic inflammatory-demyelinating diseases (IIDDs) are monophasic, multiphasic, or progressive disorders characterized by inflammatory demyelination affecting attacks different sites of the central nervous system (CNS) [1]
Characteristics of Clinically isolated syndrome (CIS) patients who relapsed during follow-up are presented in Supplementary Table S1
Of 20 CIS-R patients, seven converted to multiple sclerosis (MS) according to the 2010 McDonald’s Diagnostic Criteria; eight converted to neuromyelitis optica spectrum disorder (NMOSD) according to the 2015 Revised International Criteria; three patients were diagnosed with relapsing myelitis; one with relapsing brainstem encephalitis; and one with tumefactive demyelination
Summary
Idiopathic inflammatory-demyelinating diseases (IIDDs) are monophasic, multiphasic, or progressive disorders characterized by inflammatory demyelination affecting attacks different sites of the central nervous system (CNS) [1]. This spectrum represent a broad spectrum of CNS disorders that can be differentiated on the basis of severity, clinical course, lesion distribution, and imaging, laboratory, and pathological findings [1]. Limited information has been published concerning the evaluation of clinical risk factors for relapse in other multiphasic IIDDs. In addition, very few studies have analyzed the predictive effect of serum cytokine levels on clinical progression [6]. We detected several cytokines in the serum of CIS patients and evaluated their ability to predict second events and conversion from CIS to MS or NMOSD. The associations between serum cytokines levels and clinical findings were investigated
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