Gordana Toncev - Academia.edu (original) (raw)

Papers by Gordana Toncev

Hippokratia, 2016

BACKGROUND We report the case of a 35-year-old man with stroke related to infective endocarditis ... more BACKGROUND We report the case of a 35-year-old man with stroke related to infective endocarditis (IE) caused by Kocuria kristinae. CASE DESCRIPTION The patient with chronic hepatitis C virus infection and a former intravenous drug user developed a stroke suddenly, after three months duration of fever and malaise. Duplex ultrasonography of the carotid arteries (zero level diastolic flow, diastolic reversed flow) focused attention to cardiac valve pathology and endocarditis (definite confirmation was made by transesophageal echocardiography). Kocuria kristinae was grown from the blood culture and antibiotic therapy administered, according to the antibiogram, did not cure the infection and the patient underwent an aortic valve replacement with a mechanical prosthesis and debridement of the mitral valve. One year after the surgery, the patient had no subjective problems and neurological findings were normal. Conclusion: To our knowledge, this is the first case of IE caused by Kocuria k...

Vojnosanitetski pregled, 2020

Background/Aim. Malignant gliomas represent a heterogenaus group of tumors. They occur in all age... more Background/Aim. Malignant gliomas represent a heterogenaus group of tumors. They occur in all age groups, predominatly in males in older age. The purpose of this case-control study was to examine the association between risk for developing glioma and family history of diseases. Methods. The case-control study included 100 pathologically confirmed cases of glioma at the Clinical Centre Kragujevac, Serbia, between 2015 and 2016, and 200 ageand sex-matched controls without glioma and other malignant diseases in personal and family history at the same institution. After signing the informed consent all the patients filled out an epidemiological questionnaire. Multivariate logistic regression analysies was used in statistical data processing. Results. Malignant diseases in family history were more common in the study group than in the control group [odds ratio (OR) = 1.821, 95% confidence interval (CI) 1.004?3.305; p = 0.049]. The most common malignant tumor in the study group were cance...

Journal of Clinical Neurophysiology, 2019

PURPOSE The purpose of this study was to examine if depression and fatigue affect event-related b... more 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.

Serbian Journal of Experimental and Clinical Research, 2019

Inclusion body myositis belongs to the group of idiopathic inflammatory myopathies. Two processes... more Inclusion body myositis belongs to the group of idiopathic inflammatory myopathies. Two processes, one autoimmune and the other degenerative, appear to occur in parallel. There are two forms of inclusion body myositis, hereditary and sporadic. Case report: 47-year-old woman with muscle weakness and atrophy of the distal and proximal muscles, and involvement of quadriceps and deep finger flexors was admitted for neuromuscular evaluation. These changes have been started gradually and insidiously over three years. Electromyography findings were nonspecific and for this reason in the beginning of the disease it was misdiagnosed as demyelization peripheral neuropathy. Muscle biopsy, with the presence of characteristic structures such as rimmed vacuoles and amyloid deposits definitely confirmed the diagnosis of inclusion body myositis. Conclusion: There are several difficulties in the diagnosis of inclusion body myositis as nonspecific EMG findings and overreliance on electrophysiology an...

The Lancet Neurology, 2019

BACKGROUND Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendro... more BACKGROUND Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis. METHODS We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18-58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov, number NCT01864148. FINDINGS Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0·89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment. INTERPRETATION Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose. FUNDING Biogen.

Open Medicine, 2019

Background Cerebral small vessel disease (CSVD) and metabolic syndrome were separately associated... more 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 bei...

Acta Neurologica Belgica, 2019

Cognitive impairment frequently occurs in epilepsy patients. Patients with drug-resistant epileps... more 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.

Vojnosanitetski pregled, 2017

Introduction. Marchiafava-Bignami disease is a rare disorder mostly associated with chronic heavy... more Introduction. Marchiafava-Bignami disease is a rare disorder mostly associated with chronic heavy alcohol consumption that results in progressive demyelination and necrosis of the corpus callosum. Case report. We reported a 35-year-old woman with a history of alcohol consumption and malnutrition. Neurological examination revealed axial hypotonia, dysarthric speech and lack of motor coordination. The brain multislice computed tomography imaging demonstrated hypodense lesion of the corpus callosum. On the basis of her history, clinical features and imaging studies, the diagnosis of an acute form of Marchiava-Bignami disease was made. Definite diagnosis was confirmed at autopsy. Conclusion. Marchiafava-Bignami disease is of a medical emergency and early recognition and early aggressive treatment are critical for a good clinical outcome. To our knowledge, this is the first case of Marchiafava-Bignami disease presented with axial hypotonia.

Vojnosanitetski pregled, 2017

Backgraund/Aim. Gliomas are the most common primary brain tumors and the etiology is unknown. The... more Backgraund/Aim. Gliomas are the most common primary brain tumors and the etiology is unknown. The aim of this study was to investigate possible association between incidence in relation to glioma and certain blood groups. Methods. The case-control study included 100 pathologically confirmed cases of glioma at the Clinical centar of Kragujevac, Serbia, between 2014 and 2015, and 200 age and sex-matched controls without malignant diseases in personal and family history at the same institution. After signing the informed consent, all patients filled out an epidemiological questionnaire. Results. In the analysis comparing the glioma patients with the control group, a significant association (p < 0.0005) was observed in relation to the blood group AB. Furthermore, it was not observed a significant association in relation to the blood group A (p = 0.070), blood group B (p = 0.256), blood group O (p = 0.768) among the compared groups. Also, in the analysis comparing glioma patients with...

Multiple Sclerosis and Related Disorders, 2017

Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on cl... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;H), and additionally, to evaluate the impact of patient support program on TS and adherence. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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. Each of the TSQM summary scores in all three countries implicated high level of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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). 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.

Serbian Journal of Experimental and Clinical Research, 2016

Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS). Howeve... more Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS). However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have beneficial therapeutic effects. The aim of this study is to investigate serum uric acid levels in MS patients before and after long-term interferon beta treatment.Blood samples from 101 MS patients (53 receiving interferon beta 1a treatment and 48 receiving interferon beta 1b treatment; 28 male and 73 female; mean age at treatment onset 32,4±7,3 years; mean duration of disease at treatment onset 5,1±3,2 years; mean EDSS 2±1,3) before and after interferon beta treatment (mean treatment duration 3±2 years) were analysed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech Diagnostic, Sees, France). MS patients had significantly increased serum uric acid levels after treatment compared with those at the begin...

Serbian Journal of Experimental and Clinical Research, 2016

The therapeutic potential of cannabis has been known for centuries. Cannabinoids express their ef... more The therapeutic potential of cannabis has been known for centuries. Cannabinoids express their effects through two types of receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Present studies indicate that cannabis-based drugs can make a positive impact in the treatment of different diseases. For many years, multiple sclerosis patients have self-medicated with illegal street cannabis to alleviate spasticity, a common and debilitating symptom that impairs quality of life.Nabiximols is the cannabis-based medicine approved in many countries as an add-on therapy for symptom improvement in patients with spasticity who have not responded adequately to other medications. Adverse events such as dizziness, diarrhoea, fatigue, nausea, headache and somnolence occur quite frequently with nabiximols, but they are generally of mild-to-moderate intensity and their incidence can be markedly reduced by gradual uptitration. The prerequisite for the therapeutic use of cannabis in...

Serbian Journal of Experimental and Clinical Research, 2016

The aim of this study was to demonstrate the prevalence of abdominal aortic aneurysm in patients ... more The aim of this study was to demonstrate the prevalence of abdominal aortic aneurysm in patients with carotid disease and to analyse the influence of cardiovascular risk factors for abdominal aortic aneurysm. Methods: Ultrasound for abdominal aortic aneurysm was performed in 200 patients (112 men and 88 women, mean age 65.72±7.71 years) with known carotid disease. The primary cardiovascular risk factors (age, sex, hypertension, diabetes, dyslipidaemia and smoking) were analysed. Results: We found that 15.5% of patients with carotid stenosis also had abdominal aortic aneurysm. The prevalence of abdominal aortic aneurysm was higher in men (22.23%) than in women (6.81%). There was no correlation between the severity of carotid disease and the diameter of the abdominal aortic aneurysm (p>0.05). Advanced age and smoking were independent risk factors for abdominal aortic aneurysm. Conclusion: These results demonstrate that the prevalence of abdominal aortic aneurysm is higher in patien...

Serbian Journal of Experimental and Clinical Research, 2017

Fatigue is a common feature in a wide variety of chronic inflammatory and autoimmune diseases, bu... more Fatigue is a common feature in a wide variety of chronic inflammatory and autoimmune diseases, but fatigue in autoimmune thyroid disease (AITD) has not been investigated so far. The aim of this study was to examine fatigue in patients with AITD and to analyse the correlation between fatigue and the serum concentrations of thyroid antibodies, thyroid function and depression. This cross-sectional clinical study included 62 patients with increased concentrations of thyroperoxidase antibodies (TPOAbs) as confirmation of AITD and 52 healthy individuals who were negative for thyroid antibodies; all controls were euthyroid. Thyroid antibodies, free thyroxine and thyroid-stimulating hormone were measured in the sera of all subjects. The Fatigue Severity Scale was used to measure the severity of fatigue; the level of depression was measured by the Beck Depression Inventory. Eight (12.9%) patients had evident fatigue, 7 (11.3%) patients had fatigue limit values, and 47 (75.8%) patients had no...

Serbian Journal of Experimental and Clinical Research, 2014

ABSTRACTWe reported a case of a 22-year-old male patient with swallowing difficulties and double ... more ABSTRACTWe reported a case of a 22-year-old male patient with swallowing difficulties and double vision. He was diagnosed on the basis of a positive pharmacological test, damage to the postsynaptic neuromuscular junction and computed tomography of the thorax. Tests for antibodies targeted to acetylcholine receptors and to muscle-specific tyrosine kinase were negative. A partial improvement in neurological findings following treatment with pyridostigmine bromide, cyclosporine and methylprednisolone was notedadministered. Th e patient responded favourably to plasma exchange with a withdrawal of all clinical symptoms, confirming the hypothesis that humoral factors may underlie the pathogenesis of double-negative MG .

Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina, 2011

To determine influence of biometeorological phases on stroke incidence according to age and gende... more 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. 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. 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 le...

Serbian Journal of Experimental and Clinical Research, 2011

Vojnosanitetski pregled, 2008

Buducnost celijske terapije u lecenju neuroloskih bolesti je pocela. Ostaju vazna pitanja na koja... more Buducnost celijske terapije u lecenju neuroloskih bolesti je pocela. Ostaju vazna pitanja na koja odgovor mogu dati samo dobro osmisljene medjunarodne studije, a ticu se vrste celija, nacina njihovog umnozavanja i aplikacije, kao i optimalnog vremenskog okvira za ovakvu vrstu lecenja.

Journal of the Peripheral Nervous System, 2014

The aim of this study was to define features of Guillain-Barré syndrome in a large cohort of pati... more 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.

Hippokratia, 2016

BACKGROUND We report the case of a 35-year-old man with stroke related to infective endocarditis ... more BACKGROUND We report the case of a 35-year-old man with stroke related to infective endocarditis (IE) caused by Kocuria kristinae. CASE DESCRIPTION The patient with chronic hepatitis C virus infection and a former intravenous drug user developed a stroke suddenly, after three months duration of fever and malaise. Duplex ultrasonography of the carotid arteries (zero level diastolic flow, diastolic reversed flow) focused attention to cardiac valve pathology and endocarditis (definite confirmation was made by transesophageal echocardiography). Kocuria kristinae was grown from the blood culture and antibiotic therapy administered, according to the antibiogram, did not cure the infection and the patient underwent an aortic valve replacement with a mechanical prosthesis and debridement of the mitral valve. One year after the surgery, the patient had no subjective problems and neurological findings were normal. Conclusion: To our knowledge, this is the first case of IE caused by Kocuria k...

Vojnosanitetski pregled, 2020

Background/Aim. Malignant gliomas represent a heterogenaus group of tumors. They occur in all age... more Background/Aim. Malignant gliomas represent a heterogenaus group of tumors. They occur in all age groups, predominatly in males in older age. The purpose of this case-control study was to examine the association between risk for developing glioma and family history of diseases. Methods. The case-control study included 100 pathologically confirmed cases of glioma at the Clinical Centre Kragujevac, Serbia, between 2015 and 2016, and 200 ageand sex-matched controls without glioma and other malignant diseases in personal and family history at the same institution. After signing the informed consent all the patients filled out an epidemiological questionnaire. Multivariate logistic regression analysies was used in statistical data processing. Results. Malignant diseases in family history were more common in the study group than in the control group [odds ratio (OR) = 1.821, 95% confidence interval (CI) 1.004?3.305; p = 0.049]. The most common malignant tumor in the study group were cance...

Journal of Clinical Neurophysiology, 2019

PURPOSE The purpose of this study was to examine if depression and fatigue affect event-related b... more 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.

Serbian Journal of Experimental and Clinical Research, 2019

Inclusion body myositis belongs to the group of idiopathic inflammatory myopathies. Two processes... more Inclusion body myositis belongs to the group of idiopathic inflammatory myopathies. Two processes, one autoimmune and the other degenerative, appear to occur in parallel. There are two forms of inclusion body myositis, hereditary and sporadic. Case report: 47-year-old woman with muscle weakness and atrophy of the distal and proximal muscles, and involvement of quadriceps and deep finger flexors was admitted for neuromuscular evaluation. These changes have been started gradually and insidiously over three years. Electromyography findings were nonspecific and for this reason in the beginning of the disease it was misdiagnosed as demyelization peripheral neuropathy. Muscle biopsy, with the presence of characteristic structures such as rimmed vacuoles and amyloid deposits definitely confirmed the diagnosis of inclusion body myositis. Conclusion: There are several difficulties in the diagnosis of inclusion body myositis as nonspecific EMG findings and overreliance on electrophysiology an...

The Lancet Neurology, 2019

BACKGROUND Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendro... more BACKGROUND Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis. METHODS We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18-58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov, number NCT01864148. FINDINGS Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0·89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment. INTERPRETATION Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose. FUNDING Biogen.

Open Medicine, 2019

Background Cerebral small vessel disease (CSVD) and metabolic syndrome were separately associated... more 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 bei...

Acta Neurologica Belgica, 2019

Cognitive impairment frequently occurs in epilepsy patients. Patients with drug-resistant epileps... more 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.

Vojnosanitetski pregled, 2017

Introduction. Marchiafava-Bignami disease is a rare disorder mostly associated with chronic heavy... more Introduction. Marchiafava-Bignami disease is a rare disorder mostly associated with chronic heavy alcohol consumption that results in progressive demyelination and necrosis of the corpus callosum. Case report. We reported a 35-year-old woman with a history of alcohol consumption and malnutrition. Neurological examination revealed axial hypotonia, dysarthric speech and lack of motor coordination. The brain multislice computed tomography imaging demonstrated hypodense lesion of the corpus callosum. On the basis of her history, clinical features and imaging studies, the diagnosis of an acute form of Marchiava-Bignami disease was made. Definite diagnosis was confirmed at autopsy. Conclusion. Marchiafava-Bignami disease is of a medical emergency and early recognition and early aggressive treatment are critical for a good clinical outcome. To our knowledge, this is the first case of Marchiafava-Bignami disease presented with axial hypotonia.

Vojnosanitetski pregled, 2017

Backgraund/Aim. Gliomas are the most common primary brain tumors and the etiology is unknown. The... more Backgraund/Aim. Gliomas are the most common primary brain tumors and the etiology is unknown. The aim of this study was to investigate possible association between incidence in relation to glioma and certain blood groups. Methods. The case-control study included 100 pathologically confirmed cases of glioma at the Clinical centar of Kragujevac, Serbia, between 2014 and 2015, and 200 age and sex-matched controls without malignant diseases in personal and family history at the same institution. After signing the informed consent, all patients filled out an epidemiological questionnaire. Results. In the analysis comparing the glioma patients with the control group, a significant association (p < 0.0005) was observed in relation to the blood group AB. Furthermore, it was not observed a significant association in relation to the blood group A (p = 0.070), blood group B (p = 0.256), blood group O (p = 0.768) among the compared groups. Also, in the analysis comparing glioma patients with...

Multiple Sclerosis and Related Disorders, 2017

Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on cl... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;H), and additionally, to evaluate the impact of patient support program on TS and adherence. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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. Each of the TSQM summary scores in all three countries implicated high level of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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). 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.

Serbian Journal of Experimental and Clinical Research, 2016

Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS). Howeve... more Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS). However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have beneficial therapeutic effects. The aim of this study is to investigate serum uric acid levels in MS patients before and after long-term interferon beta treatment.Blood samples from 101 MS patients (53 receiving interferon beta 1a treatment and 48 receiving interferon beta 1b treatment; 28 male and 73 female; mean age at treatment onset 32,4±7,3 years; mean duration of disease at treatment onset 5,1±3,2 years; mean EDSS 2±1,3) before and after interferon beta treatment (mean treatment duration 3±2 years) were analysed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech Diagnostic, Sees, France). MS patients had significantly increased serum uric acid levels after treatment compared with those at the begin...

Serbian Journal of Experimental and Clinical Research, 2016

The therapeutic potential of cannabis has been known for centuries. Cannabinoids express their ef... more The therapeutic potential of cannabis has been known for centuries. Cannabinoids express their effects through two types of receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Present studies indicate that cannabis-based drugs can make a positive impact in the treatment of different diseases. For many years, multiple sclerosis patients have self-medicated with illegal street cannabis to alleviate spasticity, a common and debilitating symptom that impairs quality of life.Nabiximols is the cannabis-based medicine approved in many countries as an add-on therapy for symptom improvement in patients with spasticity who have not responded adequately to other medications. Adverse events such as dizziness, diarrhoea, fatigue, nausea, headache and somnolence occur quite frequently with nabiximols, but they are generally of mild-to-moderate intensity and their incidence can be markedly reduced by gradual uptitration. The prerequisite for the therapeutic use of cannabis in...

Serbian Journal of Experimental and Clinical Research, 2016

The aim of this study was to demonstrate the prevalence of abdominal aortic aneurysm in patients ... more The aim of this study was to demonstrate the prevalence of abdominal aortic aneurysm in patients with carotid disease and to analyse the influence of cardiovascular risk factors for abdominal aortic aneurysm. Methods: Ultrasound for abdominal aortic aneurysm was performed in 200 patients (112 men and 88 women, mean age 65.72±7.71 years) with known carotid disease. The primary cardiovascular risk factors (age, sex, hypertension, diabetes, dyslipidaemia and smoking) were analysed. Results: We found that 15.5% of patients with carotid stenosis also had abdominal aortic aneurysm. The prevalence of abdominal aortic aneurysm was higher in men (22.23%) than in women (6.81%). There was no correlation between the severity of carotid disease and the diameter of the abdominal aortic aneurysm (p>0.05). Advanced age and smoking were independent risk factors for abdominal aortic aneurysm. Conclusion: These results demonstrate that the prevalence of abdominal aortic aneurysm is higher in patien...

Serbian Journal of Experimental and Clinical Research, 2017

Fatigue is a common feature in a wide variety of chronic inflammatory and autoimmune diseases, bu... more Fatigue is a common feature in a wide variety of chronic inflammatory and autoimmune diseases, but fatigue in autoimmune thyroid disease (AITD) has not been investigated so far. The aim of this study was to examine fatigue in patients with AITD and to analyse the correlation between fatigue and the serum concentrations of thyroid antibodies, thyroid function and depression. This cross-sectional clinical study included 62 patients with increased concentrations of thyroperoxidase antibodies (TPOAbs) as confirmation of AITD and 52 healthy individuals who were negative for thyroid antibodies; all controls were euthyroid. Thyroid antibodies, free thyroxine and thyroid-stimulating hormone were measured in the sera of all subjects. The Fatigue Severity Scale was used to measure the severity of fatigue; the level of depression was measured by the Beck Depression Inventory. Eight (12.9%) patients had evident fatigue, 7 (11.3%) patients had fatigue limit values, and 47 (75.8%) patients had no...

Serbian Journal of Experimental and Clinical Research, 2014

ABSTRACTWe reported a case of a 22-year-old male patient with swallowing difficulties and double ... more ABSTRACTWe reported a case of a 22-year-old male patient with swallowing difficulties and double vision. He was diagnosed on the basis of a positive pharmacological test, damage to the postsynaptic neuromuscular junction and computed tomography of the thorax. Tests for antibodies targeted to acetylcholine receptors and to muscle-specific tyrosine kinase were negative. A partial improvement in neurological findings following treatment with pyridostigmine bromide, cyclosporine and methylprednisolone was notedadministered. Th e patient responded favourably to plasma exchange with a withdrawal of all clinical symptoms, confirming the hypothesis that humoral factors may underlie the pathogenesis of double-negative MG .

Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina, 2011

To determine influence of biometeorological phases on stroke incidence according to age and gende... more 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. 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. 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 le...

Serbian Journal of Experimental and Clinical Research, 2011

Vojnosanitetski pregled, 2008

Buducnost celijske terapije u lecenju neuroloskih bolesti je pocela. Ostaju vazna pitanja na koja... more Buducnost celijske terapije u lecenju neuroloskih bolesti je pocela. Ostaju vazna pitanja na koja odgovor mogu dati samo dobro osmisljene medjunarodne studije, a ticu se vrste celija, nacina njihovog umnozavanja i aplikacije, kao i optimalnog vremenskog okvira za ovakvu vrstu lecenja.

Journal of the Peripheral Nervous System, 2014

The aim of this study was to define features of Guillain-Barré syndrome in a large cohort of pati... more 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.