Browsing by Author "Sokić, Dragoslav (35611592800)"

Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the pro oxi dant/ antioxidant balance in epi lep sy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with la mo trigine, 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-PGF2α) 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-PGF2α 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-PGF2α 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 in creased 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 epi lepsy.

Background: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the pro oxi dant/ antioxidant balance in epi lep sy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with la mo trigine, 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-PGF2α) 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-PGF2α 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-PGF2α 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 in creased 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 epi lepsy.

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.

The aim of this study was to determine whether the occurrence of focal-to-bilateral motor seizures in the course of partial drug withdrawal during video-EEG monitoring (FTBMS-M) had a predictive value for seizure recurrence in surgically treated patients with mesial temporal lobe epilepsy (MTLE). We analyzed the outcomes of 59 patients who underwent temporal lobe resection and had postoperative follow-up from 6 to 58 months. In total, 48 out of 59 patients were rendered seizure free (81.4%). We analyzed seizure recurrence after surgery with reference to: (i) occurrence of seizures after partial drug withdrawal during video-EEG monitoring (FTBMS-M); (ii) history of secondarily generalized seizures during antiepileptic drug treatment prior to presurgical evaluation (FTBMS-H) and (iii) other possible confounding factors (sex, age, epilepsy duration, side of surgery, presence of hippocampal sclerosis, and history of febrile seizures). We found no differences in the frequency of seizure recurrences between patients with FTBMS-M and patients without FTBMS-M (4/20 vs. 7/39; p = 0.848). Conversely, the frequency of seizure recurrence was significantly higher among the patients with FTBMS-H than among the patients without FTBMS-H (7/20 vs. 4/39; p = 0.021). The predictive value of FTBMS-H for postoperative seizure recurrence was confirmed in logistic regression analysis. We found a statistically significant influence of FTBMS-H on poor outcome after surgery, but not of FTBMS-M or other confounding variables, which suggests that withdrawal seizures do not affect post-surgical seizure control. © 2020, Belgian Neurological Society.

Aim. 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. Methods. 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. Results. 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). Conclusion. 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. © 2018 Epileptic Disorders

Aim. 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. Methods. 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. Results. 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). Conclusion. 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. © 2018 Epileptic Disorders

Aims. 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. Methods. 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. Results. 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. Conclusions. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences. © 2020 Epileptic Disorders

Aims. 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. Methods. 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. Results. 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. Conclusions. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences. © 2020 Epileptic Disorders

Multinodular and vacuolating neuronal tumour (MVNT) of the cerebrum is a relatively new, well defined histopathological and neuroradiological entity, in many cases associated with an early adult-onset epilepsy. These lesions have an indolent course and resemble both malformative and neoplastic processes, combining a focal developmental anomaly and a low-grade tumour. Herein, we report a case of a 48-year-old female patient with left temporal lobe epilepsy associated with MVNT. In addition, a comprehensive review of all the previously published cases is provided with a focus on seizure-related cases, surgical treatment, and postoperative outcome. © 2019 Epileptic Disorders

Multinodular and vacuolating neuronal tumour (MVNT) of the cerebrum is a relatively new, well defined histopathological and neuroradiological entity, in many cases associated with an early adult-onset epilepsy. These lesions have an indolent course and resemble both malformative and neoplastic processes, combining a focal developmental anomaly and a low-grade tumour. Herein, we report a case of a 48-year-old female patient with left temporal lobe epilepsy associated with MVNT. In addition, a comprehensive review of all the previously published cases is provided with a focus on seizure-related cases, surgical treatment, and postoperative outcome. © 2019 Epileptic Disorders

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. © 2023

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. © 2023

Purpose: In a homogeneous cohort of mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS), this study utilizes the PETSurfer method to quantify and localize areas of cerebral hypometabolism. Methods: We selected patients from the University Clinical Center of Serbia who all underwent anterior temporal lobectomy with amygdalohippocampectomy and achieved seizure freedom (Engel class I). Our analysis involved integrating FDG-PET and MRI imaging to compare glucose metabolism between the hemispheres ipsilateral and contralateral to HS. Results: The quantitative PETSurfer approach identified significant hypometabolism restricted to the ipsilateral temporal lobe structures—the amygdala, hippocampus, temporal pole, superior and middle temporal gyrus—and the ipsilateral thalamus. The lack of significant hypometabolism in extratemporal regions indicates that these 'pure' mTLE cases may not involve the broader network disruptions typically associated with more extensive epileptic pathologies. The effect sizes ranged from small to medium, indicating variable degrees of metabolic reduction across different structures. Conclusion: These findings highlight the localized nature of the epileptogenic focus in HS-related mTLE with good surgical outcome. However, the small sample size and potential cohort bias, necessitate caution in generalizing these results. Future research would benefit from a comparative approach incorporating a control group, providing a broader context for interpreting these hypometabolic patterns. © 2024 British Epilepsy Association

Purpose: In a homogeneous cohort of mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS), this study utilizes the PETSurfer method to quantify and localize areas of cerebral hypometabolism. Methods: We selected patients from the University Clinical Center of Serbia who all underwent anterior temporal lobectomy with amygdalohippocampectomy and achieved seizure freedom (Engel class I). Our analysis involved integrating FDG-PET and MRI imaging to compare glucose metabolism between the hemispheres ipsilateral and contralateral to HS. Results: The quantitative PETSurfer approach identified significant hypometabolism restricted to the ipsilateral temporal lobe structures—the amygdala, hippocampus, temporal pole, superior and middle temporal gyrus—and the ipsilateral thalamus. The lack of significant hypometabolism in extratemporal regions indicates that these 'pure' mTLE cases may not involve the broader network disruptions typically associated with more extensive epileptic pathologies. The effect sizes ranged from small to medium, indicating variable degrees of metabolic reduction across different structures. Conclusion: These findings highlight the localized nature of the epileptogenic focus in HS-related mTLE with good surgical outcome. However, the small sample size and potential cohort bias, necessitate caution in generalizing these results. Future research would benefit from a comparative approach incorporating a control group, providing a broader context for interpreting these hypometabolic patterns. © 2024 British Epilepsy Association

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. © 2017, © 2017 The Neurosurgical Foundation.

The association of arachnoiditis ossificans with acquired peripheral nerve disease is rare. We report a case who presented with progressive myelopathy due to arachnoiditis ossificans from prior trauma, complicated with multifocal motor neuropathy. Intradural bone was removed at surgery. © 2019 The Neurosurgical Foundation.

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 (rs = − 0.73; p < 0.001). The SVLAEP and SVNDDI-E final scores had a positive moderate correlation (rs = 0.52; p < 0.001). A moderate negative statistical correlation was found between SVNDDI-E and SVQOLIE-31 (rs = − 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. © 2020 Elsevier Inc.

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 (rs = − 0.73; p < 0.001). The SVLAEP and SVNDDI-E final scores had a positive moderate correlation (rs = 0.52; p < 0.001). A moderate negative statistical correlation was found between SVNDDI-E and SVQOLIE-31 (rs = − 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. © 2020 Elsevier Inc.