Determination of systemic inflammatory biomarkers in multiple sclerosis.

Background: Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system. We aimed to investigate serum and cerebrospinal fluid levels of different laboratory inflammatory biomarkers in patients with MS. Methods: A total of 120 subjects participated in the study, 60 of whom were diagnosed with MS, 30 with the final diagnosis of non-inflammatory diseases of the central nervous system (CNS), and 30 healthy subjects representing the control group. Regarding the progression of radiological findings after 2 years from the initial diagnosis, the MS group was divided into stationary radiological findings (n=30) and radiologically proven disease progression (n=30). In all patients, we analyzed levels of laboratory inflammatory biomarkers: C reactive protein (CRP), Neutrophil-to-lymphocyte ratio (NLR), Growth differentiation factor 15 (GDF15) in serum samples, and neurofilaments (NFs) in cerebrospinal fluid (CSF). NFs and GDF15 were analyzed initially, while CRP and NLR values were analyzed initially and after two years. Results: We found statistically lower GDF15 values and initial CRP values in the MS group regarding the group with non-inflammatory diseases of the CNS (p<0.0001). On the other side, we determined a significant elevation of laboratory markers CRP and NLR, initially and after a two-year period, in the MS subgroup with the progression of magnetic resonance imaging (MRI) findings (p<0.0001 and p=0.050, respectively). Also, we found a positive correlation between CRP and NFs (r=0.243, p=0.04), as well as a positive correlation between CRP and GDF15 in patients with MS (r=0.769, p<0.0001). Conclusions: We found a significant elevation of laboratory markers of systemic inflammation, CRP, and NLR in MS patients who developed disease progression based on MRI findings. There is a need for further studies to validate current parameters to be considered as useful markers of MS activity and disability.

VALIDATION OF THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS (BICAMS) IN A LARGE COHORT OF RELAPSING-REMITTING MS PATIENTS.

Cognitive impairment is one of the most frequently reported symptoms in persons with multiple sclerosis (MS). The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been recommended as a standardized international screening and monitoring tool for brief cognitive assessment. The aim of our study was to assess the reliability and validity of the Serbian version of the BICAMS. A total of 500 relapsing-remitting MS (RRMS) patients and 69 age-, gender- and education-matched healthy control (HC) subjects were examined. All participants performed the BICAMS test battery, which includes the oral version of the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test second edition (CVLT-II), and Brief Visuospatial Memory Test Revised (BVMTR). A randomly selected subset of patients were retested one to three weeks after baseline. Statistically significant differences between patients and HCs were evident on the SDMT and BVMTR (p<0.001). HCs had higher CVLT-II scores but this difference did not reach statistical significance (p=0.063). Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was found in 62.9% of MS patients. There were statistically significant correlations between BICAMS scores and age, education, EDSS and disease duration in patient sample. Test-retest reliability was confirmed with Pearson correlation coefficient of 0.70 in all measures. This study supported the reliability and validity of the Serbian BICAMS, although the CVLT-II version tested here lacked sensitivity to detect MS compared to healthy volunteers.

The impact of betaplus program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicentric cross-sectional survey in the western Balkan countries.

BACKGROUND: Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on clinical outcomes in multiple sclerosis (MS). It has been recently emphasized that low treatment satisfaction (TS) may be an important factor for achieving high rates of treatment adherence. Interferon (IFN) beta-1b was the first DMD approved for the treatment of MS. The aims of our study were to assess TS in subjects with relapsing-remitting (RR) MS treated with IFN beta-1b in Serbia, Montenegro and the Republika Srpska, Bosnia and Herzegovina (B&H), and additionally, to evaluate the impact of patient support program on TS and adherence. METHODS: This is a cross-sectional survey performed in order to examine TS and adherence with IFN beta-1b in seven MS centers across three countries (Serbia, Montenegro and B&H). Included in the study were 296 adult patients with RRMS treated with IFN beta-1b for at least 6 months. They were invited to complete the Treatment Satisfaction Questionnaire for Medication (TSQM). Additional two treatment adherence questions were also asked. Patient support program (Betaplus®) was available exclusively for patients in Serbia and not for those in Montenegro and the Republika Srpska, B&H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&H and compared their results with those from patients in Serbia. Statistical analysis includes multivariable linear regression analysis in order to assess the differences between three MS patients groups in terms of the TSQM scores, adjusted for potential confounders. For the evaluation of the effects of Betaplus® program, multivariable logistic regression was used, controlling for the same confounding factors. RESULTS: Each of the TSQM summary scores in all three countries implicated high level of patients' satisfaction. There was statistically significant group difference on the Effectiveness summary score (p=0.001) and the Side effects summary score (p=0.006) between the group of subjects from Serbia and the combined group of subjects from Montenegro and B&H, in favor of the former cohort. There was statistically significant group difference neither on the Convenience summary score nor on the Overall satisfaction summary score. Results of adjusted logistic regression analysis based on the availability of patient support program (dependent variable) implicate that it had the most significant impact on the Effectiveness summary score (p=0.008). According to the correlation coefficients in the total patient cohort, all TSMQ summary scores except Effectiveness significantly correlated with the decreased adherence (Side effects: p=0.037; Convenience: p=0.016; Overall satisfaction: p=0.046). CONCLUSION: TS with IFN beta-1b was high in our MS patients. Additionally, these results have demonstrated that patient support program have significant impact on TS with IFN beta-1b in the Balkan cohort of RRMS patients.

Improvement of post-hypoxic action myoclonus with levetiracetam add-on therapy: A case report.

INTRODUCTION: Chronic post-anoxic myoclonus, also known as Lance-Adams syndrome, may develop following hypoxic brain injury, and is resistant to pharmacological therapy. CASE REPORT: The patient we presented developed post-anoxic action myoclonus with severe, completely incapacitating myoclonic jerks. Myoclonus did not respond to the treatment with commonly used agents, i.e. valproate and clonazepam alone or in combination. Improvement of the action myoclonus was observed only after adding levetiracetam. CONCLUSION: Although Lance-Adams syndrome may not be fully curable at this point, levetiracetam appears to be a promising agent that can significantly improve functional level and overall quality of life of patients with this disorder.