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 Prevalence of Pain in Adults with Multiple Sclerosis: A Multicenter Cross-Sectional Survey.

OBJECTIVE: Examination of prevalence, intensity and associations of pain in persons with multiple sclerosis (MS). DESIGN: Multicenter, international cross-sectional survey. SETTING: Patients were recruited from seven MS centers: in Serbia (Clinic of Neurology, Clinical Center of Serbia, Belgrade; Clinic of Neurology, Military Medical Academy, Belgrade; Clinic of Neurology, Clinical Center Kragujevac; Clinic of Neurology, Clinical Center Nis; Department of Neurology, General Hospital-Uzice), in Republic of Srpska-Bosnia and Herzegovina (Clinic of Neurology, Clinical Center Banja Luka) and in Croatia (University Department of Neurology, Sestre Milosrdnice University Hospital Center, Zagreb). SUBJECTS: Six hundred and fifty consecutive MS patients diagnosed according to the Revised McDonald criteria (2005), from the aforementioned centers, over the period of 6 months. METHODS: A semistructured questionnaire was administered during a face-to-face interview with neurologists who also performed Expanded Disability Status Scale (EDSS), the Hamilton Rating Scale for Depression (HDRS) and Hamilton Rating Scale for Anxiety (HARS). To recognize predictive factors for the presence of pain, the linear regression analysis was used. RESULTS: Lifetime prevalence of pain was 66.5% (point prevalence = 44.3%). The prevalence of the comorbidity of pain and depression was 29.1%. Older age (P < 0.001), primary-progressive MS (P = 0.034), higher EDSS score (P = 0.008), higher scores of HDRS (P < 0.001), and HARS (P < 0.001) were significantly associated with pain. Finally, in our multivariate linear regression analysis, anxiety (P < 0.001) was the independent predictor of pain. CONCLUSIONS: We confirmed high prevalence of pain, affecting approximately more than half of patients during the course of MS. Pain in MS is associated with disability, depression and, especially with anxiety, which has significant implications for treatment.

Clinical and epidemiological features of Guillain-Barré syndrome in the Western Balkans.

The aim of this study was to define features of Guillain-Barré syndrome in a large cohort of patients from three Western Balkans countries. Data from adult Guillain-Barré syndrome (GBS) cases from 2009 to 2013 were retrospectively obtained from all tertiary health care centers. During the 5-year period, 327 new cases of GBS were identified with a male to female ratio of 1.7 : 1. The most common GBS variants were demyelinating (65%) and axonal (12%). At nadir 45% of patients were chair-bound, confined to bed, or required assisted ventilation, while 5% died. The crude incidence of GBS in Serbia and Montenegro was 0.93 per 100,000 population, and age-adjusted incidence according to the world standard population was 0.86 per 100,000. Incidence was particularly high in 50- to 80-year-old men. Statistically significant seasonal variations of GBS were not observed. This study of patients with GBS in the Western Balkans allows us to prepare the health system better and to improve the management of patients. This study also opens opportunities for international collaboration and for taking part in the multinational studies on GBS.

An unusual case of aneurysmal tibial nerve compression detected in ED.

We present an unusual case of tibial nerve compression caused by a true tibial posterior artery aneurysm. A 61-year-old man was admitted to the emergency department due to suspected muscle rupture. He had experienced a sudden, intense right calf pain and swelling that had begun during walking. He had a 6-month-long history of symptoms suggestive to the tibial nerve dysfunction and a month-long history of neurologic finding consistent with the right tibial nerve paresis. An examination of the legs revealed a painful mass in the posterior-medial compartment of the right calf. Emergency ultrasound scanning of the right lower leg vascularization showed an expansive saccular aneurysm of the proximal segment posterior tibial artery with mural thrombus and splitting of the aneurysmal wall. An angiography confirmed the diagnosis. Under spinal anesthesia, we performed aneurysmectomy and decompressed the tibial nerve. The histologic examination was compatible with a true aneurysm of the right posterior tibial artery.

The impact of the comorbid seizure/epilepsy on the health related quality of life in people with multiple sclerosis: an international multicentric study.

Introduction: The health-related quality of life (HRQoL) of people with (Pw) multiple sclerosis (MS) is usually deteriorated. It has been recently suggested that comorbidities may have the negative influence on the quality of life of the PwMS, but according to the best of our knowledge, only one study investigated, although in a very small cohort, the impact of individual comorbidity on the quality of life of PwMS. The aim of our investigation was to assess, in an international, multicentric study, the impact of comorbid seizure/epilepsy on the HRQoL in PwMS. Methods: We conducted cross-sectional study at numerous neurological centers in Serbia, Croatia, Bulgaria, Montenegro, Northern Macedonia, and Bosnia and Herzegovina (Federation of Bosnia and Herzegovina and Republic of Srpska). For each patient, demographic and clinical data were collected, including Expanded disability status scale (EDSS) score. Beck Depression Inventory (BDI) and the 36-Item Short Form Health Survey (SF-36) questionnaires were administered to all patients. Results: The study comprised 326 PwMS in total, 127 PwMS with seizure/epilepsy and 209 PwMS without. Both mean Physical health composite (PHC) and mental health composite (MHC) scores, were statistically significantly higher in PwMS without seizure/epilepsy, implicating worse quality of life in PwMS with comorbid seizure/epilepsy. Presence of seizure/epilepsy in pwMS was statistically significant independent predictor of both PHC and MHC, in multivariate linear regression model after adjustment for potential confounding variables. The hierarchical multivariate regression analysis was performed in order to establish the most important predictors of the PHC and MHC of the SF-36, in PwMS with seizure/epilepsy; older age, higher level of disability, as measured by EDSS, higher depression score, drug-resistant epilepsy and shorter time since last seizure were found to significantly predict worse MHC score in PwMS with seizure/epilepsy. Discussion: Our results point to the possible role of theinterventions related to the adequate control of epilepsy along with improvement of the mental health status to be important in order to reduce MS burden in the PwMS with comorbid seizure/epilepsy.

Depression and Fatigue in Patients With Multiple Sclerosis Have No Influence on the Parameters of Cognitive Evoked Potentials.

PURPOSE: The purpose of this study was to examine if depression and fatigue affect event-related brain potentials (ERPs) in patients with relapsing-remitting multiple sclerosis, and to assess the significance of ERP as an indicator of cognitive impairment. METHODS: A total of 81 relapsing-remitting multiple sclerosis patients and 32 healthy control subjects participated in the study. Cognitive functions were evaluated using a standard PASAT, the symbol digit modality test, and ERP. The degrees of depressive symptomatology and fatigue were assessed with Beck Depression Inventory, the Fatigue Severity Scale, and the Fatigue Impact Scale. RESULTS: Fatigue and depression had a negative effect on the cognitive functions examined by neuropsychological tests. Depression and fatigue did not influence ERP amplitude and latency findings. Depression level was negatively correlated with symbol digit modality test score (r = -0.135, P < 0.05). Fatigue level was negatively correlated with the results for PASAT A (r = -0.225, P < 0.05) and PASAT B (r = -0.342, P < 0.01). Reaction time was positively associated with depression (r = 0.246, P = 0.01) and fatigue (r = 0.281, P = 0.01). CONCLUSIONS: Depression and fatigue have no effect on ERP amplitude and latency, so they cannot participate in risk assessment for the development of cognitive impairment in patients with relapsing-remitting multiple sclerosis.

Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome.

BACKGROUND: Cerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered. OBJECTIVE: The aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities. METHODS: This prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD. RESULTS: The study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone. CONCLUSIONS: In conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.

Impact of epilepsy duration, seizure control and EEG abnormalities on cognitive impairment in drug-resistant epilepsy patients.

Cognitive impairment frequently occurs in epilepsy patients. Patients with drug-resistant epilepsy (DRE) have poor drug responsivity and higher seizure frequency which consequently lead to brain damage and may have implications on cognitive status. In the present study, we assessed a frequency and degree of cognitive impairment in 52 patients with drug-sensitive epilepsy (DSE) and 103 DRE patients at three time points (baseline, after 12 and 18 months). Degree of cognitive decline was assessed with Montreal Cognitive Assessment (MoCA) scale. We examined the possible correlation between demographic and clinical characteristics and cognitive deterioration in epilepsy patients. Patients in the DRE group had significantly lower MoCA score than patients in the DSE group at baseline (28.83 ± 2.05 vs. 29.69 ± 0.61, p = 0.003), after 12 months (27.36 ± 2.40 vs. 29.58 ± 1.22, p = 0.000) and 18 months (26.86 ± 2.73 vs. 29.33 ± 1.47, p = 0.000). Patients with DRF epilepsy had significantly lower MoCA score than patients with DSF epilepsy at three time points (28.71 ± 2.48 vs. 29.86 ± 0.35, p = 0.015; 27.22 ± 2.72 vs. 29.52 ± 1.37, p = 0.000; 26.80 ± 2.99 vs. 29.31 ± 1.56, p = 0.000). After 12 and 18 months of follow-up, patients with DRG epilepsy had significantly lower MoCA score than patients with DSG epilepsy (27.52 ± 2.01 vs. 29.65 ± 1.02, p = 0.000; 26.94 ± 2.43 vs. 29.35 ± 1.40, p = 0.000). Illness duration negatively correlated with cognitive status (p = 0.005); seizure control and EEG findings positively correlated with MoCA score (p = 0.000). Illness duration, seizure control, drug responsivity, and EEG findings are significant predictors of MoCA score (p < 0.05). Clinicians have to pay attention to patients with drug-resistant epilepsy and concepts of aggressive treatment to minimize the adverse effects of epilepsy on cognition.

Potential Drug-drug Interactions in Acute Ischemic Stroke Patients at the Neurological Intensive Care Unit.

BACKGROUND: Clinically relevant potential drug-drug interactions are considered preventable adverse drug reactions. OBJECTIVE: The aim of this study was to ascertain the frequency of potential drug-drug interactions in acute ischemic stroke patients and to explore factors associated with occurrence of potentially contraindicated drug-drug interactions. METHODS: This observational retrospective cohort and nested case-control study was carried out among patients treated for acute ischemic stroke at the Neurological Intensive Care Unit in the Clinical Centre Kragujevac, Serbia. The potentially drug-drug interactions for each day of hospitalization were identifi ed using Micromedex® soft ware. Based on the existence or absence of potentially contraindicated drug-drug interactions, the participants were divided into a group of cases (n=111) and the control group (n=444). RESULTS: A total of 696 patients were analysed. All patients had a minimum of one potential drug-drug interaction during hospitalization. The most common drugs involved in potential drug-drug interactions were aspirin (8.02%), diclofenac (7.49%) and warfarin (7.14%). The number of medications prescribed for simultaneous use during hospitalisation and the use of antipsychotics in therapy signifi cantly increased the likelihood of potentially contraindicated drug-drug interactions aft er adjustment by means of logistic regression for 1.2 and 3 times, respectively. CONCLUSIONS: This study suggests that patients with acute ischemic stroke are frequently exposed to potential drug-drug interactions. It is essential to identify potentially drug-drug interactions in these patients as early as possible in order to prevent adverse drug reactions and ensure safe recovery. Besides, full attention should be paid when adding each new medication in therapy, particularly when a neurologist decides to prescribe antipsychotics, such as risperidone.

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.

Biometeorological phases influence on stroke morbidity.

AIM: To determine influence of biometeorological phases on stroke incidence according to age and gender of patients, place of residence, days in a week, months in a year, type of stroke, additional diagnosis. METHODS: Comparative analysis of the data on stroke patients (according to age, months, days, place of residence, age, sex, stroke type, additional diagnosis and number of hospitalization days) obtained by examining the records of discharge and admission of patients in the Department of Neurology of Kragujevac and everyday biometeorological phases obtained from the Republic Hydrometeorological Service of Serbia (RHMS of Serbia), for the following years: 2003, 2004, 2007, 2008 and 2009 in Kragujevac. RESULTS: 4,700 patients diagnosed with stroke were hospitalized in the observed period. The highest number of strokes was noted in 2003 (1,030), the lowest in 2008 (851). The highest number of strokes was in March (444) and the lowest in February (351).The most frequent days were Mondays (805), and the least frequent Sundays (495). Three fifths of patients were from urban areas and the rest of them were from rural areas. Out of this number 2,382 (50.7%) were males and 2.318 (49.3%) were females, of which 1.847 (77.6%) males and 1,894 (81.7%) females were over 70 years old. The average number of hospitalization days was 12.29 days, and most patients were in hospital for less than 10 days (2101 patients). 4,130 (87.9%) patients were diagnosed with thromboembolism, 422 (9.0%) with intracerebral hemorrhage and 148 (3.2%) with subarachnoid hemorrhage. As an additional diagnosis 1,946 (41.4%) patients had hypertension, 867(18.6%) had heart insufficiency and 15.40% had diabetes. Most strokes with significant correlation were in biometheorological phases 9 and 4 (1,227 and 1,010 strokes) and the least were in phase 10 (29). As a daily average, the highest number of strokes was in phase 8 (2.76/ day), the lowest in phase 2 (2.33/day). CONCLUSIONS: Biometeorological phases have a great influence on stroke incidence, especially in phases with stable sunny weather and sudden impact of weather fronts, with sudden weather changes, with average incidence in the phase of foggy weather.

High-dose methylprednisolone therapy in multiple sclerosis increases serum uric acid levels.

Uric acid, which is the final product of purine nucleoside metabolism, is a strong peroxynitrite scavenger. Several studies report on lower serum uric acid levels in multiple sclerosis. In this study, we investigated serum uric acid levels before and after high-dose methylprednisolone treatment (intravenous 1 g/day/5 days) in multiple sclerosis patients. Blood samples from 25 definite multiple sclerosis patients (11 male and 14 female) before and after methylprednisolone treatment (days 0, 6 and 30) and from 20 healthy donors (9 male and 11 female) were analyzed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech diagnostics, Sees, France) according to the manufacturer's protocol, and the results were standardized using a commercial uric acid standard solution. We observed significantly increased serum uric acid levels 1 day after the termination of the therapy (day 6). These differences were sustained for 30 days after starting treatment (during remission period). Mean serum uric acid levels were significantly higher in the control group. These results suggest that increasing the uric acid concentration may represent one of the possible mechanisms of action of methylprednisolone in multiple sclerosis.