Predictive value of early serum cytokine changes on long-term interferon beta-1a efficacy in multiple sclerosis.

BACKGROUND: In a previous study, we had evaluated short-term effects of interferon beta-1a (IFNB-1a) 44 µg s.c. three times per week treatment on serum levels of IFN-gamma (IFNG), IL-23, IL-17, IL-10, IL-9, IL-4 and TGF-beta (TGFB) and found a reduction only in IL-17 and IL-23 levels after 2 months of treatment. METHODS: Using the same multiple sclerosis (MS) cohort, we assessed the predictive value of early cytokine level changes (difference between 2nd month and baseline levels as measured by ELISA) on the efficacy of long-term IFNB-1a treatment. RESULTS: The alteration in IFNG levels of patients without any relapse was statistically lower than that of patients having one or more relapses (p = 0.019, Student's t-test). When patients with or without expanded disability severity scale (EDSS) progression were compared, none of the cytokine level changes showed a significant difference between groups. IL-17 and IL-23 level changes did not predict relapse and EDSS progression in IFNB-1a-treated MS patients. CONCLUSION: Our results show that the predictive power of early IFNG measurement on relapse occurrence may potentially extend a time span of several years.

Effect of short-term interferon-ß treatment on cytokines in multiple sclerosis: significant modulation of IL-17 and IL-23.

Therapeutic effect of interferon-ß (IFN-ß) treatment has been associated with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg) cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple sclerosis (MS) has not been studied. To investigate the short-term effects of IFN-ß treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL-10, IL-4, IFN-γ, IL-9 and TGF-ß in relapsing remitting MS patients before and 2 months after IFN-ß treatment by ELISA. MS patients showed increased IL-17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy controls. IFN-ß treatment only reduced IL-17 and IL-23 levels, whereas the levels of other cytokines remained unchanged. IFN-ß treatment appears to exert its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS pathogenesis needs to be further studied.

Restless Legs Syndrome in Patients with Behçet's Disease and Multiple Sclerosis: Prevalence, Associated Conditions and Clinical Features.

INTRODUCTION: To investigate the prevalence and characteristics of Restless Legs Syndrome (RLS) in patients with Behçet's Disease (BD) and Multiple Sclerosis (MS). METHODS: Consecutive patients with BD and MS seen in the outpatient clinic were included in the study. As a control group, volunteer subjects without a known peripheral or central nervous system disorder were included. The BD group was divided into two sub-groups as BD with neurological involvement [Neuro-Behçet's Disease (NBD)] and BD without any neurological involvement (other BD) for further evaluation. Data on demographic characteristics, medical history and family history were collected, and all patients underwent neurological examination. The patients were evaluated for the presence of diagnostic criteria for RLS. The features and severity of RLS were evaluated in patients with RLS using Restless Legs Syndrome Identification Form, and the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale. The clinical and radiological findings of patients with BD and MS were retrieved from their medical files. RESULTS: The study included a total of 96 patients with BD (mean age 39.9±11.8; 51 males; 41 patients with NBD) and 97 patients with MS (mean age 34.97±4.1 years; 24 males). There were 100 healthy control subjects (mean age 36.18±11.10 years; 46 males). RLS was more prevalent in MS (22.8%) and NBD (22%) groups compared to the control group (10%; p=0.004 and 0.029, respectively) with a statistically significant difference. The prevalence of RLS was higher in MS patients with less disability. Most severe RLS symptoms were observed in the MS group. The rate of sleep disorders was also higher in MS group. Although stress appeared to be a factor worsening RLS in all groups, its prevalence was higher in the MS group (p=0.011). There was no correlation between the distribution of magnetic resonance imaging lesions and RLS in both MS and NBD groups. CONCLUSIONS: It is well established that RLS can accompany disorders involving the peripheral and central nervous systems such as all types of peripheral neuropathy, myelopathy, and Parkinson's disease. The present study showed that MS and NBD also seem to be a risk factor for RLS, being associated with more severe symptoms.

Comparative clinical characteristics of early- and adult-onset multiple sclerosis patients with seizures.

Multiple sclerosis (MS) and epilepsy are common disorders, the co-occurrence of which has been of considerable interest. This study aimed to evaluate the prevalence and clinical features of epileptic seizures in patients with definite MS including those with pediatric onset (≤16 years of age). Out of 2,300 patients with definite MS followed in our outpatient clinic, 36 with epileptic seizures were identified. In this cohort, 8 out of 146 pediatric cases had seizures. The clinical and demographic features of the patients were recorded. Multiple logistic regression model with the occurence of seizures as the dependent variable was performed to identify the risk factors for seizure occurrence in MS patients. The prevalence of epileptic seizures was 1.5% in definite MS patients, 1.3% in adult-onset (comparable to seizure prevalence in the general population) and 5.5% in pediatric MS patients (≤16 years old). Twenty-six of 36 (72%) patients with MS and epilepsy developed recurrent seizures after the first epileptic seizure. Mean annual relapse rate (p ≤ 0.001), mean expanded disability status scale (EDSS) score (p = 0.004) and the ratio of patients with pediatric onset (p = 0.01) were higher in MS patients with seizures. In the multiple logistic regression analysis, age at MS onset and EDSS at the last examination were found to be predictors of seizure occurrence. Occurrence of seizures during the clinical course of MS appears to be associated with early-onset and increased disease severity and might be coincidental in adults.

Enhanced complement consumption in neuromyelitis optica and Behçet's disease patients.

The complement system is essential in the pathogenesis of inflammatory central nervous system disorders. To investigate the involvement of complement pathways in neuromyelitis optica (NMO), levels of breakdown products for classical (C4d), alternative (FBb) and common (sC5b-9) pathways were measured in the sera of 28 NMO and control patients (30 Behçet's disease (BD), 29 multiple sclerosis (MS)) and 31 healthy controls by ELISA. Classical and/or alternative pathway consumption was enhanced in NMO and BD patients as compared to MS patients and healthy controls. Our results suggest that NBD and NMO differ from MS by the predominance of complement system involvement.

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients.

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis.