Serum Concentrations of Chemokines CCL20, CXCL8 and CXCL10 in Relapsing-Remitting Multiple Sclerosis and Their Association with Presence of Antibodies against Epstein-Barr Virus.

Epstein-Barr virus (EBV) infection and various chemokines, including CCL20, CXCL8 and CXCL10 are considered to participate in the pathogenesis of multiple sclerosis (MS), and several studies point to a direct regulatory effect of EBV on the expression of these chemokines. In our study we hypothesized that serum concentrations of CCL20, CXCL8 and CXCL0 are induced in patients with relapsing-remitting MS (RRMS) in comparison to healthy individuals, and that they are associated with EBV infection. Serum concentrations of CXCL8 and CXCL10 were lower in RRMS patients in relapse in comparison to healthy controls. Although potential effects of corticosteroid therapy introduced in a subgroup of RRMS patients prior to sampling were excluded by subgroup comparison, this possibility has to be considered while interpreting the results. We found an inverse association between serum concentrations of CXCL8 and anti-Epstein-Barr Virus Nuclear Antigen (EBNA) IgG and decreased expression of CXCL8 in peripheral blood mononuclear cells (PBMC) in relapse compared to remission. Lower serum concentrations of CXCL8 and CXCL10 in RRMS patients and decreased peripheral production of CXCL8 in relapse may indicate compensatory anti-inflammatory counter-regulation in MS.

Weather patterns and occurrence of epileptic seizures.

BACKGROUND: The results of various studies that have so far evaluated the influence of meteorological conditions on seizures are often divergent. No studies have been performed so far that evaluate the possible correlation between the occurrence of seizure-related events, surface and upper level atmospheric conditions and biometeorological forecasts. The aim of this study is to investigate those interactions. METHODS: Records of "Sveti Duh" University hospital, Zagreb, Croatia between January 2016 and May 2020 were analysed in order to determine number of patients per day who were assessed through Emergency room because of a recent epileptic seizure. The dates were assessed for surface and upper level atmospheric conditions and biometeorological forecasts. Analyses of these factors were performed for two consecutive days preceding that day, the day of seizure, as well as for the following day. Data was analysed using chi-squared test, Mann-Whitney U-test or Kruskal-Wallis test (with Conover's test for post-hoc analyses), depending on variable type. Additionaly, logistic regression was used to study effects of variables on seizure occurrence. Statistical significance was set to p < 0.05. RESULTS: Results showed significant difference between the numbers of patients with seizure depending on upper level type on the following day. We also observed fewer daily patients with seizures when the synoptic situation on the following day was high pressure field then when it was low pressure or non-gradient pressure field (observed just during the colder part of the year), which was supported in our regression analyses. A greater frequency of seizures was observed if the biometerological prognosis was deemed unfavourable on the following day. Furthermore, our results showed significantly larger proportion of days with seizure patients in warmer, than in colder days of the year. CONCLUSIONS: All of the analyzed weather-related parameters seem to be associated with daily numbers of seizures on the previous day. The reason behind this phenomenon is uncertain; however, the results indicate that weather patterns have a certain influence on patients with epilepsy, but are not yet fully understood or adequately appreciated.

The Prevalence of Depression in Dementia Syndrome.

BACKGROUND: It is estimated that up to 90% of patients with dementia are affected by behavioral and psychiatric symptoms during the course of the disease. The aim of this study was to investigate the prevalence of depression in dementia and mild cognitive impairment (MCI), the use of benzodiazepines and antidepressants among them and the impact of former education on their cognitive decline. SUBJECTS AND METHODS: In the study we have enrolled 100 patients with clinical diagnoses of either MCI or dementia, as was established by a single cognitive neurology subspecialist. All patients were assessed during their regular outpatient follow-ups in the University Clinical Center Zagreb, Croatia, in the period between November 2019 and March 2020. Using the patients' medical history the demographic data, disease characteristics, history of other diseases, use of medications, Mini-Mental State Examination (MMSE) and the data on radiological brain examinations were obtained. The statistical tests were used depending on the distribution of variables. RESULTS: In total, there were 34 patients diagnosed with dementia and 66 diagnosed with MCI. The diagnosis of depression before the onset of dementia or MCI was established in 11% and it has developed in further 20% after cognitive deterioration, which represents an increase of 81.81%. The total prevalence of depression in the study group is thus 31%.The proportion of patients taking benzodiazepines was 26% and antidepressants 17%.The MMSE scores were significantly lower in patients with Alzheimer's disease than in patients with vascular MCI or dementia. Generally, MMSE values correlated significantly with the duration of education. CONCLUSIONS: Depression is a frequent accompanying disease of dementia that aggravates already complex clinical picture and greatly diminishes the quality of life of the patient. It is important to monitor changes in a patient's cognitive decline and presence of psychiatric symptoms in order to give medical professionals a better chance to alleviate the complex issues that arise during the management of this specter of diseases.

Epidemiology of Pharmacological Treatment of Multiple Sclerosis in Croatia.

Treatment of multiple sclerosis has been a dynamic field lately, with many new and emerging treatment options. In this study, we investigate the use of disease modifying therapies (DMTs) for multiple sclerosis in Croatia. The data on DMT use was provided by the Agency for Medicinal Products and Medical Devices of Croatia (HALMED). The data from 2005 to 2016 was available. Consumption of DMTs (in DDD/1000/day) has been increasing by 9% annually on average since 2005. In the same period, the annual cost for those drugs has been increasing by 14.6% annually on average. The consumption of IFN-beta 1-a has been increasing by a much steeper rate than IFN-beta 1-b. Until 2010 the consumption of glatiramer acetate has been negligible, with a steep increase between 2011 and 2014, and a steady rate of consumption since. Recently, several new DMTs became available, namely dimethyl fumarate, teriflunomide and fingolimod. Natalizumab became available after 2010, and its consumption has been growing steadily, but its consumption figures are exceeded by alemtuzumab. New DMTs are not as readily available in Croatia as they are in some countries. However, there is a continuous increase in the number of prescriptions, along with growing costs in pharmacological treatment of multiple sclerosis, and this can be expected to become even more pronounced in the following years, due to the abundance of new therapeutic options that are steadily becoming available.

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrations of sFas and sFasL were determined in the sera of 44 and cerebrospinal fluid (CSF) of 11 relapsing-remitting (RR) MS patients using cytometric bead-based array, and their association with the disease characteristics was determined. ANA were detected in the sera of 43.2% of RRMS patients, and their frequency was the highest in patients with disease duration of less than one year (88,89%). In addition, the number of experienced relapses was lower in ANA-positive patients. Concentrations of sFasL were inversely associated with patients' expanded disability status scale (EDSS) scores. Low concentrations of both soluble factors strongly discriminated patients with moderate to severe disability, from patients with mild or absent disability only in a group of patients with prolonged disease duration (>10 years). Both soluble mediators were significantly higher in ANA-positive patients. FasL concentrations were inversely associated with the number of relapses. There is a potential link between the presence of ANA and peripheral lymphocyte apoptosis mediated by Fas/FasL system in MS, whose precise role and significance needs to be determined by future mechanistic studies.