Search

Introduction: Next generation sequencing (NGS) has greatly expanded our understanding of genetic contributors in multiple epilepsy syndromes, including focal epilepsy. Describing the genetic architecture of common syndromes promises to facilitate the diagnostic process as well as aid in the identification of patients who stand to benefit from genetic testing, but most studies to date have been limited to examining children or adults with intellectual disability. Our aim was to determine the yield of targeted sequencing of 5 established epilepsy genes (DEPDC5, LGI1, SCN1A, GRIN2A, and PCHD19) in an extensively phenotyped cohort of focal epilepsy patients with normal intellectual function or mild intellectual disability, as well as describe novel variants and determine the characteristics of variant carriers., Patients and Methods: Targeted panel sequencing was performed on 96 patients with a strong clinical suspicion of genetic focal epilepsy. Patients had previously gone through a comprehensive diagnostic epilepsy evaluation in The Neurology Clinic, University Clinical Center of Serbia. Variants of interest (VOI) were classified using the American College of Medical Genetics and the Association for Molecular Pathology criteria., Results: Six VOI in eight (8/96, 8.3%) patients were found in our cohort. Four likely pathogenic VOI were determined in six (6/96, 6.2%) patients, two DEPDC5 variants in two patients, one SCN1A variant in two patients and one PCDH19 variant in two patients. One variant of unknown significance (VUS) was found in GRIN2A in one (1/96, 1.0%) patient. Only one VOI in GRIN2A was classified as likely benign. No VOI were detected in LGI1., Conclusion: Sequencing of only five known epilepsy genes yielded a diagnostic result in 6.2% of our cohort and revealed multiple novel variants. Further research is necessary for a better understanding of the genetic basis in common epilepsy syndromes in patients with normal intellectual function or mild intellectual disability., Competing Interests: Declaration of Competing Interest Authors declare that they have no known financial interests, affiliations, or personal interests or beliefs, that could be perceived to affect the objectivity or neutrality of the manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To perform a follow-up study of the quality of life in patients with epilepsy in the era of the COVID-19 crisis., Methods: Two months before the first case of the COVID-19 in Serbia, we obtained the Serbian Version of Quality of Life Inventory for Epilepsy 31 (SVQOLIE-31) and Neurological Disorders Depression Inventory for Epilepsy scores (SVNDDI-E) for another study. We retested the same patients one year after in COVID-19 pandemic. In addition to SVQOLIE-31, and SVNDDI-E we used a generic questionnaire compiled from items related to the COVID-19., Results: We retested 97 out of 118 patients (82.2%) for the follow-up analysis. The average age was 36.1 ± 12.2 (range: 18-69), and 49 were women (50.5%). The median duration of epilepsy was 13 years (range: 1.5-48). The structural etiology of epilepsy was noted in 41 (42.3%), unknown etiology in 41 (42.3%), and genetic etiology in 15 (15.4%) patients. Fewer patients (27.8%) experienced at least one seizure three months before follow-up testing when compared to patients who experienced at least one seizure three months in initial testing (36.0%) (p = 0.15). All patients reported full compliance with anti-seizure medication in the follow-up. The SVQOLIE-31 score during the COVID-19 pandemic visit (64.5 ± 14.6) was significantly lower than the SVQOLIE-31 score before the pandemic (p < 0.001). The SVNDDI-E score during the COVID-19 pandemic (10.5 ± 3.5) was significantly higher than the SVNDDI-E score before it (p < 0.001). Multiple linear regression analyses revealed fear of seizures, and fear of a reduction in household income, significantly associated with SVQOLIE-31 and SVNDDI-E overall score. These variables accounted for 66% and 27% of the variance of SVQOLIE-31 and SVNDDI-E overall score., Significance: Lower quality of life, higher prevalence of depression, healthcare availability issues, and perceived fears during pandemic all suggest COVID-19 has negatively impacted lives of patients with epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Liverpool Adverse Event Profile (LAEP) is a useful instrument in assessing the consequences of adverse events in patients using antiseizure medication. The LAEP scale has been validated in several languages to date. The aim of our study was to validate the LAEP scale in the Serbian language (SVLAEP). Validation of the SVLAEP scale was conducted by translating the original English version into the Serbian language and backtranslated into the English language. The translation was accepted when the two versions of the text were compatible. The questionnaire is then given to a group of patients with epilepsy treated with a stable dose of antiseizure medication. For the assessment of the quality of life and depression, we used the Serbian version of the Quality of Life in Epilepsy Inventory-31 (SVQOLIE-31) and the Serbian version of the Neurological Disorders Depression Inventory for Epilepsy (SVNDDI-E). From a total of 166 patients, 118 patients were included, and the remaining 48 were excluded because of other comorbidities and using other psychotropic drugs. Internal consistency (Cronbach's α = 0.87) and test-retest reliability (intraclass correlation coefficient (ICC) = 0.80) were satisfactory. The SVLAEP and SVQOLIE-31 had a strong negative statistical correlation (r s  = -0.73; p < 0.001). The SVLAEP and SVNDDI-E final scores had a positive moderate correlation (r s  = 0.52; p < 0.001). A moderate negative statistical correlation was found between SVNDDI-E and SVQOLIE-31 (r s  = -0.56; p < 0.001). Our study showed that the LAEP scale is a useful indicator for the frequency of the adverse events in antiepileptic drug (AED) usage, despite a minor overlap with the symptoms of depression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p<0.001). Based on a significant difference in major clinical variables, that may well affect postoperative results, the similar postsurgical seizure outcome in groups with and without EPE observed in our study should be considered with caution, and conclusions as to whether there is value in formal presurgical evaluation in LEAT patients cannot be drawn. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences.

Due to a limited number of patients with drug-resistant parietal lobe epilepsy in surgical series, there are insufficient data about long-term seizure outcome following surgery restricted to the parietal lobe. We performed a meta-analysis to asses long-term outcomes in patients with parietal lobe epilepsy who underwent surgery confined to the parietal lobe or resection with major involvement of the parietal cortex. An English language literature search for studies on parietal lobe surgery and outcome was conducted using the MEDLINE database, followed by a manual search based on specific criteria. An inverse variance random effect meta-analysis model was used to estimate the pooled proportion of Engel Class I. Meta-regression models were used to examine the association between outcome and potential predictors. The search yielded seven retrospective studies with a total sample size of 253 patients (mean follow-up: 104.9±74.8 months). Following surgery, Engel Class I surgical outcome was achieved in 62.4% (95% CI: 0.492-0.755). Two independent predictors were identified for positive long-term outcome: interictal EEG localized to the parietal region (p=0.007) and the presence of tumour (p=0.022). Following surgery confined to the parietal lobe or resection with major involvement of the parietal cortex, the long-term prognosis of patients with parietal lobe epilepsy is favourable.

Background: Using a group of young healthy individuals and patients with multiple sclerosis (pMS), we aimed to investigate whether the physical attractiveness judgment affects perception of epilepsy. We tested hypothesis that subjects, in the absence of relevant clues, would catch upon the facial attractiveness when asked to speculate which person suffers epilepsy and select less attractive choices., Method: Two photo-arrays (7 photos for each gender) selected from the Chicago Face Database (180 neutral faces of Caucasian volunteers with unknown medical status) were shown to study participants. Photos were evenly distributed along a continuum of attractiveness that was estimated by independent raters in prestudy stage. In each photo-array, three photos had rating 1-3 (unattractive), one photo had rating 4 (neutral), and three photos had rating 5-7 (attractive). High-quality printed photo-arrays were presented to test subjects, and they were asked to select one person from each photo-array "who has epilepsy". Finally, all subjects were asked to complete questionnaire of self-esteem and 19-item Scale of stereotypes toward people with epilepsy., Results: In total, 71 students of psychology, anthropology, or andragogy (mean age: 21.6±1.7years; female: 85.9%) and 70 pMS (mean age: 37.9±8years; female: 71.4%) were tested. Majority of students or pMS had no previous personal experience with individuals with epilepsy (63.4%; 47.1%, p=0.052). Male photo was selected as epileptic in the following proportions: students - 84.5% unattractive, 8.5% neutral, and 7% attractive; pMS - 62.9% unattractive, 8.6% neutral, and 28.6% attractive (p=0.003). Female photo was selected as epileptic in the following proportions: students - 38% unattractive, 52.1% neutral, and 9.9% attractive; pMS - 32.9% unattractive, 34.3% neutral, and 32.9% attractive (0.003). Both groups showed very low potential for stigmatization: significantly lower in pMS in 10 items. Patients with multiple sclerosis showed significantly higher self-esteem than students (p=0.007)., Conclusion: Facial attractiveness influences the perception of diagnosis of epilepsy. Both students and pMS were less willing to attribute epilepsy to attractive person of both genders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed and proven efficient for the rapid detection of a major depressive episode in people with epilepsy. This study describes the development, validation, and psychometric properties of the NDDI-E Serbian version. A consecutive sample of 103 patients with epilepsy was assessed using the Beck Depression Inventory (BDI) and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Serbian version. Cronbach's alpha coefficient was 0.763. Receiver operating characteristic analysis showed an area under the curve of 0.943 (95% CI; 0.826 to 0.951), a cutoff score of ≥14, a sensitivity of 72.2%, a specificity of 95.2%, a positive predictive value of 81.3%, and a negative predictive value of 94.3%. The NDDI-E Serbian version scores were significantly and positively correlated with those of the BDI (p<0.001). The NDDI-E Serbian version constitutes a concise and consistent depression screening instrument for patients with epilepsy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The diagnosis of epilepsy primarily depends on description of the observed seizure. The aim of this study was to determine the reliability of witness' description among groups with different medical education., Methods: A group of 44 respondents (15 laymen, 15 medical students, and 14 doctors at neurology residency program) were shown video footages of focal epileptic seizure (ES) with secondary generalization and psychogenic non-epileptic seizure (PNES) of the same patient. The ability to describe ES and PNES characteristics, to estimate duration of seizures, and to detect of accurate seizure type was evaluated using a questionnaire. For the analysis of primary data obtained from questionnaires, we used descriptive statistical methods and methods for testing statistical hypotheses., Results: The sensitivity (Sn) and specificity (Sp) for accurate recognition of ES are different in the examined groups (laymen Sn  =  53.3%, Sp  =  33.3%; medical students Sn  =  100%, Sp  =  13.3%; neurology residents Sn  =  100%, Sp  =  71.4%). Evaluated duration of PNES and ES do not differ between examined groups. The impression that ES and PNES are distinct events is reciprocal for medical students and neurology residents, but not in laymen group. Neurology residents notice the essential characteristics of ES in high percentage., Conclusion: Accurate classification of the attacks is associated with the observers' level of medical knowledge. Witnesses with specific, neurological knowledge with higher probability, compared to the laity and medical students, differentiate ES from PNES.

Purpose: The application of artificial neural networks in the pharmaceutical sciences is broad, ranging from drug discovery to clinical pharmacy. In this study, we explored the applicability of counter-propagation artificial neural networks (CPANNs), combined with genetic algorithm (GA) for prediction of topiramate (TPM) serum levels based on identified factors important for its prediction., Methods: The study was performed on 118 TPM measurements obtained from 78 adult epileptic patients. Patients were on stable TPM dosing regimen for at least 7 days; therefore, steady-state was assumed. TPM serum concentration was determined by high performance liquid chromatography with fluorescence detection. The influence of demographic, biochemical parameters and therapy characteristics of the patients on TPM levels were tested. Data analysis was performed by CPANNs. GA was used for optimal CPANN parameters, variable selection and adjustment of relative importance., Results: Data for training included 88 measured TPM concentrations, while remaining were used for validation. Among all factors tested, TPM dose, renal function (eGFR) and carbamazepine dose significantly influenced TPM level and their relative importance were 0.7500, 0.2813, 0.0625, respectively. Relative error and root mean squared relative error (%) and their corresponding 95% confidence intervals for training set were 2.14 [(-2.41) - 6.70] and 21.5 [18.5 - 24.1]; and for test set were -6.21 [(-21.2) - 8.77] and 39.9 [31.7 - 46.7], respectively., Conclusions: Statistical parameters showed acceptable predictive performance. Results indicate the feasibility of CPANNs combined with GA to predict TPM concentrations and to adjust relative importance of identified variability factors in population of adult epileptic patients.

The objective of the study was to develop population pharmacokinetic model of topiramate (TPM) using nonlinear mixed effects modelling approach. Data were collected from 78 adult epileptic patients on mono- or co-therapy of TPM and other antiepileptic drugs, such as carbamazepine (CBZ), valproic acid, lamotrigine, levetiracetam, phenobarbital and pregabalin. Steady-state TPM concentrations were determined in blood samples by high performance liquid chromatography with fluorescence detection. A one-compartment model with first order absorption and elimination was used to fit the concentration-time TPM data. Volume of distribution of TPM was estimated at 0.575 l/kg. The influence of demographic, biochemical parameters and therapy characteristics of the patients on oral clearance (CL/F) was evaluated. Daily carbamazepine dose (DCBZ) and renal function estimated by Modification of diet in renal disease (MDRD) formula significantly (p<0.001) influenced CL/F and were included in the final model: CL/F · (l/h)=1.53(l/h) · [1+0.476 · DCBZ(mg/day)/1000(mg/day)] · EXP[0.00476 · [MDRD(ml/ min)-95.72(ml/min)]]. Increase of CL/F with DCBZ and MDRD was best described by linear and exponential models. Mean TPM CL/F during CBZ co-therapy was 2.46 l/h, which is higher for 60.8% than in patients not co-treated with CBZ. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by adequate plots and indicated satisfactory precision. This model allows individualisation of TPM dosing in routine patient care, especially useful for patients on different CBZ dosing regimen., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Interrelationship between sleep and epilepsy presents in the best way the delicate konjuction of physiologic and pathologic mechanisms underlying both of the states. In the II century it was Galen who pointed to the detrimental effect of sleep deprivation on the frequency of epileptic attacks. This empiric formulation is important even today in the counceling of patients with epilepsy. The research of the sleep process generated better understanding of the basic mechanisms of epilepsies. Sleep deprivation worsens the control of epileptic attacks which in turn destroy sleep structure and impede the daily functioning of the epileptic patients.

Purpose: We report the frequency of parkinsonism and cognitive decline (P/CD) in patients treated with valproate (VPA) after 1 year of treatment and at least 1 year of follow-up., Methods: Three hundred sixty-four patients with various epileptic syndromes and seizure types were treated with VPA mono- or polytherapy for more than 1 year., Results: We found five cases of P/CD (1.37%; 95% CI, 0.18-2.56%). Among 140 patients with different adverse effects (AEs) of VPA, P/CD were among the rarest in frequency but significant in terms of drug discontinuation (five of 17)., Conclusions: Early identification of this type of AE and discontinuation of the drug led to complete recovery in affected patients.

Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the pro oxidant/ antioxidant balance in epilepsy, a comparative analysis of the byproducts of oxidative damage and antioxidant defense mechanisms was performed in patients with epilepsy treated with lamotrigine, carbamazepine and valproic acid. Methods: Byproducts of oxidative damage to proteins (reactive carbonyl derivatives, RCD and protein thiol groups, PSH), lipids (urinary isoprostanes, 8-epi-PGF2a) and DNA (urinary 8-hydroxy-2’-deoxyguanosine, 8-OHdG), as well as the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in 60 patients with newly diagnosed seizure (at illness onset and after 6 months of treatment with lamotrigine, carbamazepine or valproic acid) and in 20 healthy controls. Results: In patients with epilepsy, RCD, urinary 8-epi-PGF2a and 8-OHdG, together with SOD and GPX activities were significantly increased, while P-SH were only slightly decreased. After 6 months of treatment with AEDs, a decrease was observed in RCD, urinary 8-epi-PGF2a and 8- OHdG to values slightly higher or similar to the control, while P-SH remained unchanged. A decrease was also observed in SOD and GPX activities, although they remained significantly increased compared to controls. Conclusions: The results of this study have shown that treatments with lamotrigine, carbamazepine and valproic acid affect the prooxidant/antioxidant balance in patients with epilepsy.

INTRODUCTION Psychogenic nonepileptic seizure (PNES) is a sudden change in a person's behavior, perception, thinking, or feeling that is usually time limited and resembles, or is mistaken for, epilepsy but does not have the characteristic electroencephalographic (EEG) changes that accompanies a true epileptic seizure [1]. It is considered that PNES is a somatic manifestation of mental distress, in response to a psychological conflict or other Stressors [2]. A wide spectrum of clinical presentation includes syncope, generalized tonic-clonic seizure, simple and complex partial seizure, myoclonic seizure, frontal lobe seizures and status epilepticus [3]. Coexistence of epilepsy and PNES is seen in approximately 9% of cases [5]. Between 25-30% of patients referred to tertiary centers and initially diagnosed as refractory epilepsy were on further examination diagnosed as PNES [6,7]. In DSM-IV [12] PNES are usually categorized under conversion disorder with seizures or convulsions. However, psychiatric basis of PNES may be anxiousness (panic attack), somatization or factitious disorder, simulation, dissociative disorders and psychosis [1]. AIM The aim of the study was to establish clinical phenomenology and EEG characteristics as well as basic psychiatric disorder in patients with PNES. METHOD In a retrospective study covering the period from January 1st 1999 till April 31 st 2003, 24 patients (22 female, 2 male) treated at the Institute of Neurology in Belgrade were analyzed. PNES were defined as sudden change in behavior incoherent with epileptiform activity registered on EEG. Possible PNES were determined on the basis of history data and clinical examination during the attack but definitive confirmation was established only by the finding of no ictal EEG changes during typical seizure of each patient. Patients with coexisting epilepsy were included in the study, too. At least two standard EEG (range 2-6, median 4) were performed at the beginning of diagnostic evaluation. Demographic data, clinical presentation (apparent loss of consciousness, type of convulsion and associated clinical signs) and placebo-induced seizures (administration of saline near the cubital vein) with EEG or video-EEG monitoring were analyzed. Basic psychiatric disorder was classified according to DSM IV classification criteria. RESULTS Duration of PNES was 4.7 years (range from 2 months to 30 years). The time from onset to the diagnosis of PNES was 4.5 years. Epilepsy comorbidity was diagnosed in 9 patients (37.5%). The average time of use of antiepileptic drugs (AED) in the group of isolated PNES was 2.4 years and 20% of patients were treated with two or more AED. The vast majority of patients presented with bilateral convulsions (54.16%) with apparent loss of consciousness found in 91.6% of cases. Ictal iwury (16.7%), tongue bite (4.2%) and premonition of the seizure (17.4%) were uncommon. Variability in clinical presentation of seizures was found in over half of patients (57%). Psychological trigger could be determined in over 60% of patients. EEG findings in a group with isolated PNES suggesting the existence of epileptiform activity was found in one case. EEG monitoring of placebo-induced seizure was performed in 20 patients, of whom 19 (95%) showed typical habitual attack with no electroclinical correlate. In 70% of cases conversion disorder DSM-IV criteria were fulfilled. Somatization disorder and undifferentiated somatoform disorder were found in 3 patients. The diagnosis of factitious disorder was made in one case and only two patients were undiagnosed according to DSM-IV. DISCUSSION Average delay from onset to diagnosis of PNES in larger studies was estimated to be approximately 7 years [8]. Even though diagnostic delay in our study was shorter, organizational reasons for this could not be found. Longer duration of a typical attack (compared to the epileptic seizure), apparent loss of consciousness, bilateral convulsion behavior and significant clinical variability in absence of typical epileptic elements such as tongue bite and ictal iwury could be the main clinical manifestation of PNES. We found rare interictal abnormalities (6.7%) in the group with isolated PNES and significant percentage (77.7%) in patients with coexisting epilepsy which is coherent with other reports [8]. The latest could lead to prolonged delay in appropriate diagnosis and suitable treatment. Clear psychological trigger wasn't noted in whole group of patients (61 %). This, however, is not unusual since PNES represents a chronic disorder with repeated triggering that could lead to less significant role of the same psychological trigger in developed PNES. Even insufficiently resolved in ethical terms, placebo-induced procedure was of huge sensitivity. In clinical practice conversion disorder is hard to differ from malingering or implementation of secondary gain. One could make the conclusion only on the basis of detailed and careful estimation of the symptoms developing context Conversion disorder is more prevalent among women (from 2:1 to 10:1) [4, 13] but modest percentage of affected men could be explained only by limited sample in this study. CONCLUSION PNES is often replaced with epilepsy and in number of cases clinical differentiation is not easy. One should be acquainted with clinical presentation of PNES as well as its psychiatric origin in order to adequately recognize and treat the disorder.

In patients with partial seizures controlled-release vs. conventional carbamazepine had better efficiency, based on an excellent tolerance favorable daily dosage and superior compliance.

Introduction. It is considered that around 20%-30% of patients of all ages and in all continents have wrong epilepsy diagnoses. Diagnostic and consequential therapeutic errors appear, most often, when an adequate diagnostics is not applied. Benign focal epilepsy of childhoods with centrotemporal spikes-rolandic epilepsy, brings very often to diagnostic and therapeutic problems because of persistence of epilepticforms changes in an electroencephalography (EEG) recording, several years after establishment of good control over seizures. Case report. We presented 8.5 years-old girl, with the first and the only epileptic seizure at the age of 5, during her sleep. With a clear correlation of EEG record, benign rolandic epilepsy was diagnosed, so the therapy with valproate was introduced. There were no seizures after three years of its implementation. Because of epileptic-forms changes that still persisted in EEG record during her sleep, it was suggested to further use valproate. However, after reconsidering all circumstances it was concluded that the AED should bee slowly reduced up to its exclusion. After a complete stoppage of the therapy, the patient did not have any epileptic seizure for nine months, although EEG still remained pathologically changed during her sleep. Conclusion. A changed EEG record in a patient with rolandic epilepsy must not be a predictor of continuation of antiepileptic drugs therapy, after 2-3 years of successful seizures remission.

We report good outcome after surgical treatment of two patients with meningoencephalocele associated with pharmacoresistant temporal lobe epilepsy. Surgical management of meningoencephaloceles may result in seizure freedom, although optimal surgical strategy is still controversial. [ABSTRACT FROM AUTHOR]

Unverricht-Lundborg disease (ULD) is an autosomal recessive disorder caused by dodecamer repeat expansion in the promoter region of the cystatin B ( CSTB) gene in approximately 90% of the disease alleles worldwide. This study presents results of genetic findings in four Serbian unrelated patients with clinical and molecular diagnosis of ULD. Using newly established PCR protocol with betaine, we detected a homozygous expansion of dodecamer repeats in the CSTB gene in four patients with clinical diagnosis of ULD. Our results are in agreement with previous studies showing that dodecamer repeats expansion is the most common mutation associated with ULD. Haplotype analysis of eight unrelated ULD chromosomes was performed using seven markers flanking CSTB gene and one intragenic variant. We demonstrated the existence of a founder effect, strongly supported by LD calculations. Size of the minimal common haplotype implies that the most recent common ancestor of the Serbian ULD patients lived about 110 generations ago. We showed that Serbian ULD patients share the same common ancestor with patients from Baltic countries and North Africa. In the light of our data, we proposed extended minimal common haplotype, which could be considered as initial haplotype of the founder event common for Serbian, Baltic, and North African ULD patients. [ABSTRACT FROM AUTHOR]

To determine long-term survival in patients with status epilepticus (SE). We prospectively followed patients admitted for the first (69.6%) or recursive episode of SE between January 1, 1989 and December 31, 1997 at the Institute of Neurology, Belgrade, Serbia, until death or study termination (December 31, 2006). Data were obtained for cause of death; etiology of SE—acute symptomatic (AS), progressive symptomatic (PS), remote symptomatic (RS), and idiopathic/cryptogenic (I/C); presence of epilepsy; and reoccurrence of SE. Standardized mortality rate (SMR), survival, and regression analysis were used. A total of 120 of 750 patients with an episode of SE (15.9%) died in the 30-day period following SE. Data for 207 of 630 (32.8%) surviving patients (35.7% with initial SE) were available at the end of follow-up [median 12 years; 95% confidence interval (CI) 11.1–12.8]. SMR was significantly increased (SMR = 1.81; 95% CI 1.32–2.41). There were 46 deaths (22.2%): 15 of 65 in the AS, 20 of 29 in the PS, 6 of 29 in the RS, and 5 of 75 in the I/C groups. Five-year survival rate was lowest in the PS (45%) compared to AS (91%), RS (87%), and I/C (99%) groups. The following characteristics increased long-term risk for mortality: older age [Exp(B) 1.05, 95% CI 1.029–1.072], PS and AS etiology [Exp(B) 15.6, 95% CI 5.8–41.6; 3.3, 95% CI 1.2–9.1], presence of epilepsy [Exp(B) 2.3, 95% CI 1.2–4.3], and initial SE [Exp(B) 2.4, 95% CI 1.4–4.4]. Approximately one of five patients die within 12 years after an episode of SE. Symptomatic SE (PS and AS), initial SE, age, and presence of epilepsy are associated with long-term increased risk of death. [ABSTRACT FROM AUTHOR]

: We report on genetic analysis of a complex condition in a Serbian family of four siblings, wherein two had progressive myoclonic epilepsy (PME) and congenital deafness (CD), one had isolated congenital deafness (ICD), and one was healthy. : Molecular diagnosis performed by Southern blotting confirmed Unverricht-Lundborg disease in the available sibling with PME/CD. In the sibling with ICD (heterozygote for expansion mutation in CSTB) we demonstrated recombination event between the D21S2040 marker and the CSTB gene and identified c.207delC (p.T70Xfs) mutation in the fourth exon of the transmembrane protease, serine-3 (TMPRSS3) gene (maps in close proximity to CSTB), responsible for nonsyndromic deafness in the sibling with PME/CD as well. : To the best of our knowledge this is the first genetic confirmation of the coexistence of these two mutations. [ABSTRACT FROM AUTHOR]