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Introduction Surgical treatments for people living with epilepsy have the potential to provide patients with an opportunity to achieve relief from seizures, thus improving their quality of life, but they are not free of complications. The psychiatric consequences are a significant concern because of the potential risks; however, psychotic illnesses have not received adequate research compared to anxiety and depression. Objectives To better identify the psychiatric side effects that can develop following epilepsy surgery, especially psychosis, and to take preventive measures to mitigate its occurrence. Methods Presentation of a patient’s case and reviewing existing literature regarding de novo psychosis following epileptic surgery. Results The case of interest is a 31-year-old male patient who, or his relatives, has had no history of psychiatric disorders. From age 21, the patient had focal to bilateral seizures, which were preceded by olfactory auras and could occur up to 4-5 times a week and was then diagnosed with epilepsy. In June 2021, the patient underwent a right anterior temporal lobectomy for his medically resistant seizures after a presurgical evaluation and had a notable decrease in the number of seizures, occurring only during periods of sleep every six months. In the fourth month following the operation, the patient began experiencing auditory hallucinations characterized by negative and judgmental voices. After that, he engaged in an aggressive act by holding a knife and assaulting another person in a public area. He was admitted to an inpatient psychiatry service for 12 days with a diagnosis of a psychotic episode. His symptoms significantly improved, and he was discharged with paliperidone 6 mg/daily treatment. After five months, he discontinued the medication, subsequently experiencing a recurrence of auditory hallucinations and aggression. The patient was admitted to the inpatient psychiatric clinic in June 2022 as a result of experiencing paranoid delusions and engaging in a suicide attempt by self-inflicted wrist laceration using a razor blade, which was consistent with the patient’s delusional beliefs. Following 13 days of hospitalization, he was discharged with amisulpride 800 mg/daily in addition to his antiepileptic treatment. After 15 months of discharge, he showed no signs of active psychotic features, and his functioning was moderate to good. Conclusions Current research and reporting of psychiatric outcomes are limited, and the predictive factors and prognosis of psychiatric symptoms in these patients remain obscure. Long-term follow-up is crucial, especially considering the possibility of psychiatric symptoms developing in the months following surgery, as demonstrated by the current case. In addition, preoperative and postoperative assessments may facilitate the management of psychiatric symptoms. Disclosure of Interest None Declared

Purpose: Information on COVID-19 vaccine tolerance and complications in patients with epilepsy is not yet sufficient to provide a recommendation for vaccination guidelines. The aim of this study was to investigate the effect of two types of COVID vaccines currently used in Turkey (mRNA vaccine from Pfizer/BioNTech and inactivated vaccine from Sinovac) on epileptic seizures., Methods: We included 318 patients with epilepsy who were admitted to our epilepsy outpatient clinic. Clinical characteristics such as age, gender, age at seizure onset and the duration of epilepsy were noted. Types and the numbers of the anti-seizure drugs were recorded. Patients were evaluated either by face-to-face or by teleconference interviews. The seizure frequency in the first thirty days after any dose of vaccination was questioned., Results: A total of 318 patients (149 females, 46.8%) with a confirmed diagnosis of epilepsy were enrolled in the study. An increase in seizure frequency was reported after the COVID-19 vaccine in 19 patients. Of these 19 patients, 2 were vaccinated with Sinovac, while 17 were vaccinated with BioNTech/Pfizer mRNA vaccine. There was no significant relationship between age, age at seizure onset, duration of epilepsy, type of seizures, seizure frequency or seizure induction. Status epilepticus was not reported in any of the participants., Conclusion: Physicians need strong scientific evidence to advocate the importance of vaccine for COVID-19, that's why accumulation of knowledge related to this issue is important not only from medical but also from medico-legal point of interest. We aimed to contribute the current literature with our study to strengthen the physicians' hand while recommending COVID vaccines to PWE. Our results show that there is no significant increase in the risk of triggering seizures with COVID-19 vaccines. These data show that vaccination against COVID-19 with both vaccine types in patients with epilepsy is safe and well tolerated., Competing Interests: 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., (© 2024 The Authors.)

Introduction: This report examines the effects of a multimodal rehabilitation program which includes cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters., Case Description: A 22-year-old patient presented with sensory loss in the dominant left hand and reduced writing ability after right temporo-parietal lobe resection. Cognitive, motor, and sensory evaluations were carried out pre and post-treatment. The patient's spontaneous electroencephalo-gram (EEG) and an EEG during application of transcutaneous electrical nerve stimulation (TENS) (TENS EEG) were recorded. As a reference for the patient's electrophysiological values, EEGs of 4 healthy individuals were also taken. Over a period of 1 year, the patient received multimodal rehabilitation which includes cognitive, physical, and somato-sensory rehabilitation on 2 days each week., Outcomes: An improvement of the patient's cognitive capacities, motor strength, superficial, deep and cortical sensations was achieved. After rehabilitation, an increase in parietal and occipital alpha activity as well as in frontal and parietal beta activity was seen both in spontaneous EEG and in TENS EEG. With increasing TENS intensity, alpha and beta power increased as well., Conclusion: Our findings suggest that a multimodal rehabilitation program may improve cognitive, sensory, and motor effects after resection due to tumor surgery.

Objective: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE)., Methods: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum., Results: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs., Significance: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine., (© 2023 International League Against Epilepsy.)

Background: Lesional posterior cortex epilepsy (PCE) is often drug resistant and may benefit from surgical intervention. In this study, we aimed to identify potential predictive factors associated with seizure recurrence after epilepsy surgery in lesional PCE., Methods: We retrospectively reviewed patients with PCE who underwent surgery between 1998 and 2021. They were divided into 2 groups according to seizure outcome; the seizure-free group (group 1) and the non-seizure-free group (group 2). The relationship among clinical factors, electroencephalography (EEG) or cranial magnetic resonance imaging findings, disease, and seizure outcome was investigated., Results: A total of 60 patients, with a mean age of 27.26 ± 12.35 years (range, 9-61 years), were included in the study. There were 31 patients (51.66%) in group 1 (Engel class I) and 29 patients (48.33%) in group 2 (13 [21.66%], 10 [16.66%], and 6 [10%] patients in Engel class II, III, and IV, respectively), with a mean follow-up of 8.95 ± 6.96 years (range, 1-24 years). No difference was observed regarding age, gender, age at seizure onset, operation type, treatment gap, and presence of bilateral lesions between the groups (P > 0.05). However, bilateral findings on interictal EEG and gliosis as the underlying disease were predictors of seizure recurrence (P < 0.05)., Conclusions: More than half of the patients (including 2 with bilateral magnetic resonance imaging lesions) were seizure free at long-term follow-up. However, patients with bilateral findings on interictal EEG and gliosis were more likely to have recurrent seizures after surgery. Because lesional PCE is almost always drug resistant and has a potential for favorable outcomes, epilepsy surgery should be considered early., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Epilepsy is a chronic condition characterized by recurrent seizures. Despite miscellaneous antiseizure medications, resistance to treatment is still approximately 30%. This resistance brings forward the multidisciplinary approach and complementary treatments. In this study, we aimed to investigate the effect of olfactory training on epileptic seizures with special aromas having antiseizure effects in patients diagnosed with drug-resistant epilepsy., Methods: A total of 24 patients (14 pediatric and 10 adults) with drug-resistant epilepsy were recruited for the study. Participants were asked to inhale the standardized bottle filled with lavender aroma (Lavandula Angustifolia) twice a day (morning and evening) for 30-45 s (2 cm in front of nose; 10-15 s to right and left nostril and 10-15 s to both nostrils) for 3 months. The type, frequency, duration of seizures, the quality of life (SF-36 and PedsQL 4.0), and olfactory functions (Sniffin' Sticks Test and Pediatric Smell Wheel) were re-assessed., Results: Statistical analysis showed that olfactory training decreased the seizure frequency (p < 0.001) and the seizure duration (p = 0.02). A global 50% seizure reduction was seen among patients. Moreover, olfactory training increased the quality of life (p = 0.003) and improved the olfactory function in both the pediatric and adult groups (p = 0.017, p = 0.05, respectively). There was no adverse reaction and no increase in seizure frequency., Significance: The observations of the present investigation suggest that olfactory training is a successful complementary therapy with no adverse reaction in patients with drug-resistant epilepsy. Large cohort studies and longer follow-up periods are needed for providing olfactory training as a therapy modality in patients with epilepsy., (© 2022. Fondazione Società Italiana di Neurologia.)

Objectives: To describe 18 F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ( 18 F-FDG PET/MRI) along with semiology and electroencephalography (EEG) in patients with gray matter heterotopia (GMH); to evaluate the concordance between 18 F-FDG PET/MRI and clinical epileptogenic zone (EZ)., Materials & Methods: GMH (subcortical heterotopia [SCH] and periventricular nodular heterotopia [PNH]) patients with epilepsy who underwent 18 F-FDG PET/MRI were retrospectively enrolled. Two radiologists evaluated brain MRI, while two nuclear medicine specialists assessed the 18 F-FDG PET. The SUVmax values of visually hypometabolic cortical areas were compared to the contralateral cortex using a SUVmax threshold value of 10%; the SUVmax values of GMH lesions were compared with that of the right precentral gyrus. The cortex or GMH with hypometabolism on 18 F-FDG PET/MRI was considered representative of the EZ. The clinical EZ was identified using EEG and semiology., Results: Thirty patients (19 PNH; 11 SCH) with a mean age of 28.46 ± 9.52 years were enrolled. The heterotopic nodules were ametabolic in 3 patients (10%), hypometabolic in 16 (33.33%), isometabolic in 13 (26.66%), and hypermetabolic in 4 (10%). 18 F-FDG PET/MRI demonstrated hypometabolism in the cortex and GMH in 22/30 (73.33%) and 16/30 (53.33%). We could identify a clinical EZ in 18 patients, and 15 out of 18 (83.33%) had concordant 18 F-FDG PET/MRI findings., Conclusion: Heterotopic nodules in GMH patients show different metabolic patterns on 18 F-FDG PET/MRI, with nearly three-quarters of the patients having cortical hypometabolism. 18 F-FDG PET/ MRI findings are mostly concordant with the clinical EZ., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: COVID-19 is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which neurological complications have been increasingly recognized. Acute symptomatic epileptic seizures and status epilepticus are frequently reported neurological complications associated with this infection. The nervous system damage caused by SARS-CoV-2 may be mediated by the immune system. Interleukin 6 (IL-6), an important component of the cytokine storm, is directly correlated with the severity of symptoms. Tocilizumab is an inhibitor of IL-6 receptors, which blocks IL-6-mediated signal transduction and is used in the treatment of COVID-19 and status epilepticus., Case Report: A patient with the Unverricht-Lundborg disease is presented who had developed refractory recurrent status epilepticus during COVID-19 infection, which was finally controlled by treatment with tocilizumab., Discussion: Tocilizumab, an IL-6 inhibitor, may be considered as a treatment option in patients with status epilepticus and refractory seizures., (© 2022 European Academy of Neurology.)

Aim: To present one of the largest retrospective cavernoma related epilepsy (CRE) studies which include divergent supratentorial locations operated and followed up at least 2 years. We also investigated the factors affecting the seizure outcome., Material and Methods: This study includes a total of 56 patients with drug-responsive (n=40) and drug-resistant (n=16) CRE who underwent resective surgery. Age at seizure onset, age at surgery, gender, duration of epilepsy, seizure frequencies/type before and after treatment, EEG and brain MRI findings, prescribed AEDs, preoperative and post-operative neurological status, histopathological diagnosis, post-operative seizure outcomes and surgical information were documented., Results: The average follow-up period was 69.6 months (range 24-216 months). The seizure outcome was assessed according to Engel?s classification at the last follow-up. Engel class I was achieved in 53 patients (95%); there was one patient at class II and two patients at class III. All patients in the drug-responsive group were at Engel class I after the surgery, while all patients at Engel classes II and III were in the drug-resistant patient group. This clearly shows that there were better outcomes in DRP group (p < 0.01). Neither the locations of cavernomas nor the duration of epilepsy had any impact on seizure outcome (p > 0.05)., Conclusion: An earlier surgical intervention may prevent the patients from becoming drug-resistant such that their chances of being seizure free after surgery increase.

Aim: To investigate and compare the efficacy and safety of vagus nerve stimulation (VNS) therapy in different types of epilepsy., Material and Methods: Patients, who were implanted with VNS between the years 2005 and 2020, were retrospectively included in the study. Age, gender, age at seizure onset, epilepsy types, VNS implantation year, replacement year, pre and post-VNS seizure frequency, number of responders, number of antiseizure medication and adverse events were recorded., Results: In total, 41 patients were included in the study. The number of patients with focal epilepsy was 21 (51.2%). 10 patients (24.4%) had generalized epilepsy and 10 patients (24.4%) had ?combined generalized and focal epilepsy? (Lennox-Gastaut, Dravet syndrome). The Pre-VNS median seizure frequency was 1.5/day in the focal group, 0.6/day in the generalized group and 6/day in the combined group. Seizure frequencies dropped to 0.3/day in the focal group, 0.2/day in the generalized group and 3.0/day in the combined group at the 12th month after VNS (p < 0.001, p=0.004, p < 0.001). The response rate was found to be 68.3% at the 12th month after VNS. The number of antiseizure medications was decreased from 3.6/day to 3.1/day at the 12th months after VNS (p < 0.001). Two patients? (4.9%) VNS therapy was discontinued due to adverse events., Conclusion: The study indicates that VNS therapy is safe and effective in focal, generalized and combined epilepsy types. Despite having a low seizure freedom rate, VNS is a good alternative treatment option for patients who for any reason are not candidates for resective surgery.

Lafora disease (LD) is a severe form of progressive myoclonus epilepsy inherited in an autosomal recessive fashion. It is associated with biallelic pathogenic variations in EPM2A or NHLRC1, which encode laforin and malin, respectively. The disease usually starts with adolescent onset seizures followed by progressive dementia, refractory status epilepticus and eventually death within 10 years of onset. LD is generally accepted as having a homogenous clinical course with no considerable differences between EPM2A or NHLRC1 associated forms. Nevertheless, late-onset and slow progressing forms of the disease have also been reported. Herein, we have performed clinical and genetic analyses of 14 LD patients from 12 different families and identified 8 distinct biallelic variations in these patients. Five of these variations were novel and/or associated with the LD phenotype for the first time. Interestingly, almost half of the cases were homozygous for the rare rs769301934 (NM&#95;198586.3(NHLRC1): c.436 G > A; p.(Asp146Asn)) allele in NHLRC1. A less severe phenotype with an onset at a later age may be the reason for the biased inflation of this variant, which is already present in the human gene pool and can hence arise in the homozygous form in populations with increased parental consanguinity., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3 rd and 6 th months). IR group: Pregnant rats were exposed to radiation on the 17 th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3 rd month, IR-6 th month, and IR+HT-3 rd month groups vs control group. Synapses were significantly increased in the DG of HT-3 rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.

Telemedicine (TM) is the use of telecommunications' technologies to provide medical information and services. Telehealth (TH) permits broader and psychosocial support for patients and their families. We aimed to highlight the importance of the use of TH for all aspects of epilepsy, either for the scientific aspects (e.g., research, education, care, management, etc.) or for the social matters (e.g., education, sensitization, association support, etc.). There is a deep gap in knowledge and use of TH in the developing and developed countries. Epilepsy is a condition responsible for 1% of the global burden of disease. More than 50 million people have epilepsy, and barriers to care include shortage of human resources, medical facilities, and resources. Eighty (80) percent of people with epilepsy (PWE) live in low- and middle-income countries. Telehealth has the potential of addressing limited resources and improving access to PWE across the globe., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Kufs disease is the major adult form of neuronal ceroid lipofuscinosis, but is rare and difficult to diagnose. Diagnosis was traditionally dependent on the demonstration of characteristic storage material, but distinction from normal age-related accumulation of lipofuscin can be challenging. Mutation of CLN6 has emerged as the most important cause of recessive Kufs disease but, remarkably, is also responsible for variant late infantile ceroid lipofuscinosis. Here we provide a detailed description of Kufs disease due to CLN6 pathogenic variants. We studied 20 cases of Kufs disease with CLN6 pathogenic variants from 13 unrelated families. Mean age of onset was 28 years (range 12-51) with bimodal peaks in teenage and early adult life. The typical presentation was of progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures. Patients became wheelchair-bound with a mean 12 years post-onset. Ataxia was the most prominent motor feature. Dementia appeared to be an invariable accompaniment, although it could take a number of years to manifest and occasionally cognitive impairment preceded myoclonic seizures. Patients were usually highly photosensitive on EEG. MRI showed progressive cerebral and cerebellar atrophy. The median survival time was 26 years from disease onset. Ultrastructural examination of the pathology revealed fingerprint profiles as the characteristic inclusions, but they were not reliably seen in tissues other than brain. Curvilinear profiles, which are seen in the late infantile form, were not a feature. Of the 13 unrelated families we observed homozygous CLN6 pathogenic variants in four and compound heterozygous variants in nine. Compared to the variant late infantile form, there was a lower proportion of variants that predicted protein truncation. Certain heterozygous missense variants in the same amino acid position were found in both variant late infantile and Kufs disease. There was a predominance of cases from Italy and surrounding regions; this was partially explained by the discovery of three founder pathogenic variants. Clinical distinction of type A (progressive myoclonus epilepsy) and type B (dementia with motor disturbance) Kufs disease was supported by molecular diagnoses. Type A is usually caused by recessive pathogenic variants in CLN6 or dominant variants in DNAJC5. Type B Kufs is usually associated with recessive CTSF pathogenic variants. The diagnosis of Kufs remains challenging but, with the availability of genetic diagnosis, this will largely supersede the use of diagnostic biopsies, particularly as biopsies of peripheral tissues has unsatisfactory sensitivity and specificity.

Object: To analyse the clinical, imaging and histopathological data of patients who were diagnosed to have Dysembrioplastic Neuroepithelial Tumour (DNET) and underwent surgery between 1995-2015., Materials and Methods: Age at seizure onset, age at surgery, gender, disease duration, seizure outcome of 44 patients were analysed together with Magnetic Resonance Imaging (MRI) of 21 patients. MRI types were classified as type 1 (cystic/polycystic-like, well-delineated, strongly hypointense T1), type 2 (nodularlike,heterogeneous), type 3 (dysplastic-like, iso/hyposignal T1, poor delineation, gray-white matter blurring)., Results: Histopathological classification revealed simple form in 19, complex in 14 and non-specific in 11 patients. Lobar distribution of the lesions was as follows: 21 Temporal (47.7%), 12 parietal (27.3%), 8 frontal (18.2%) and 3 occipital (6.8%). Type 1 MRI was observed in 10, type 2 was in 7, and type 3 in 4 patients on radiological evaluation. All cases with type 1 MRI corresponded to either simple or complex forms and all cases with type 3 MRI corresponded to nonspecific form. The histopathological distribution of cases with type 2 MRI was 4 as non-specific, 2 as simple, 1 as complex. There was no significant difference in the age of onset, age at operation and duration of epilepsy between the patients with different MRI subtypes. The majority of patients (N:36) had Engel I outcome (81,8%). In groups with Engel II and III outcome, duration of epilepsy was significantly higher (p:0,014) and simple form of DNET has significantly higher seizure freedom after surgery compared to complex and nonspecific forms of DNET (p:0,002)., Conclusion: Patients with DNET constitute a group with favorable outcomes after epilepsy surgery especially with early referral to surgery. Longer duration of epilepsy was associated with worse seizure outcome for DNET patients. There was significant correlation between radiological and histopathological types of DNET especially in type 1 and 3.

Objective: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart., Methods: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor., Results: Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period ( p = 0.02). Mean disease duration at surgery decreased by 5.2 years ( p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7)., Conclusion: Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend., (© 2018 American Academy of Neurology.)

Introduction: Recent ILAE classification defined focal cortical dysplasia (FCD) patients with accompanying epileptic lesions as a separate group. We investigated data of patients with sole FCD lesions regarding long-term seizure outcome and different characteristics of FCD type 1 and type 2 patients., Methods: Eighty children and adult patients underwent surgery for FCD were included to the analysis of factors differentiating FCD type 1 and type 2 groups and their effect on long-term outcome., Results: FCD type 2 patients had earlier epilepsy onset (8.1 vs. 6.1 years. p=0.019) and underwent surgery younger than type 1 (18.2 vs. 23.7 years. p=0.034). FCD type 2 patients were more prominently MR positive (77.8% vs. 53.8%. p=0.029), which increased within FCD type 2 group as patients become younger (p=0.028). FCD Type 1 lesions showed mostly multilobar extension and FCD type 2 mostly located in frontal lobe. Seizure freedom was achieved in 65.4% of FCD type 1 patients and 70.4% of FCD type 2 patients. Seven patients had permanent de novo neurological deficits. Mean follow-up time was 5.5 years (Range: 1-11 years)., Conclusion: Surgical intervention in carefully selected patients may facilitate favorable seizure outcome leading to better quality of life. FCD type 1 and type 2 groups present with evident differences, which may promote medical and surgical management of these pathologies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Surgical results regarding MRI-negative epilepsy were presented and related clinical and histopathological parameters were discussed., Methods: Thirty-six MRI-negative epilepsy patients were retrospectively analyzed. Histopathological specimens were re-reviewed by 2 blind neuropathologists and re-classified based on the current classifications., Results: The mean age at surgery and seizure onset was 24.5 years and 9.3 years, respectively. Eight patients were younger than 18 years. Mean duration of seizures was 15.3 years. All but 2 underwent invasive monitorization. Eighteen patients had hypometabolism on FDG-PET with temporal lobe involvement in majority (66.7%). Hypometabolism was found in all patients with hippocampal sclerosis (HS), which was present in 50% and 66.7% of focal cortical dysplasia (FCD) type I and II patients, respectively. The frontal lobe resection was the most frequent type of operation followed by resections in temporal, parietal and occipital lobes. In 7 patients, multilobar resection was performed. Histopathological diagnosis was FCD type I, II, III, HS, and gliosis in 14, 12, 2, 3 and 2 patients, respectively. The mean follow-up was 5.8 years. Seventeen patients were seizure free and favorable outcome (Engel's I and II) was found in 69.7%. FCD type I tend to have more favorable seizure outcome. Duration of epilepsy and hypometabolism on FDG-PET was significantly related to outcome, whereas involved lobe was not., Conclusions: Our results suggest it is worth pursuing resective surgery in adults as well as in children with drug-resistant epilepsy with normal MRI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients., Method: Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies. Age at examination, gender, age at onset, seizure frequency, risk factors, seizure precipitants, and type of seizures were noted. Plasma obtained from patients was frozen at -80°C and analysed for autoantibodies against VGKC-complex, VGCC, GAD, LGI1, CASPR2, NMDA, AMPA and GABAB receptors with immunocytochemistry and radioimmunoassay as required., Results: Thirteen (13.8%) patients, but none of the controls, had antibodies (p=0.003). Antibodies were directed against the uncharacterized components of VGKC-complex in 5 patients (5.3%), GAD in 4 patients (4.2%), NMDA-R in 1 patient (1%), AMPA-R in 1 patient (1%) and both GAD and VGKC-complex in 2 patients (2.1%). Prognosis of epilepsy, in subsequent follow-up, did not correlate to general presence of anti-neuronal antibodies with slightly more patients with antibodies epilepsy control than without (76.9% vs. 69.1%, not-statistically significant. Three patients with suspected active autoimmunity and epilepsy who were treated, showed a response to treatment with a reduction in the seizure frequency. Although most clinical features were identical between seropositive and seronegative patient groups, seropositive patients were more likely to have inflammatory/autoimmune disorders in their medical history., Discussion: In keeping with previous studies, we have shown anti-neuronal antibodies in a proportion of focal epilepsy patients. Although autoimmunity might merely occur as a bystander effect in many chronic neurological disorders, association of anti-neuronal antibodies with good response to immunotherapy and coexisting autoimmune disorders suggests that anti-neuronal autoimmunity might participate in seizure formation at least in a subgroup of focal epilepsy patients., Conclusion: Immunity may play a role in some patients with unknown etiology regardless of prognosis and immunmodulatuar treatment may be helpful in seropositive group., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Such neuropsychiatric symptoms as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD), intellectual disability, aggression, and epilepsy are very common in patients with tuberous sclerosis complex (TSC). Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, is a recent and effective treatment for TSC patients with giant cell astrocytomas and renal angiomyolipoma, and it has been shown to have a potential to reduce tumor volume. However, there is a paucity of studies on the effects of everolimus on neuropsychiatric symptoms. The aim of the present study is to describe the effects of everolimus on emotional and behavioral symptoms and refractory epilepsy in a group of patients with TSC., Methods: Four boys and two girls (median age 16.5; range 7.5-23 years) were included in the study. Information on the clinical and treatment characteristics of the patients was gathered from the medical records., Results: Median everolimus dose was 10 mg/day (range 5-20 mg) and median time for follow-up was 17.5 (range 7-26) months. The drug was well tolerated with mild adverse effects, including stomatitis (three cases), increase in triglycerides and cholesterol (two cases), and constipation (one case). The adverse effects encountered during the course of treatment did not make it necessary to discontinue the drug or decrease its dose. All cases experienced very good to moderate response for controlling epileptic seizures. Besides, improvements in social contact, language, repetitive behavior, inattention, hyperactivity, and depression were observed in some patients., Conclusions: Everolimus was well tolerated without severe adverse effects. It was helpful in controlling seizures and additional improvements were noted in autistic, ADHD, and depressive symptoms.

Purpose: The present study aimed to determine if the specific characteristics of fluorodeoxyglucose-positron emission tomography (FDG-PET) analyses of the FCD subgroups were compatible with the magnetic resonance imaging (MRI) and clinical findings of the patients in these subgroups., Methods: This study included 71 patients who had a presurgical evaluation workup performed due to drug-resistant seizures, who underwent epilepsy surgery, and who were histopathologically diagnosed with FCD. Relationships involving MRI and FDG-PET findings and clinical data from pathological subgroups and patients were assessed., Results: According to the International League Against Epilepsy (ILAE) classifications of FCD, 28 of the patients were type I and 43 were type II. FCD was visible on the MRI scans of 53 patients, and a majority of this group was classified as type II FCD (n=34). Of these 53 patients, FCD was located in the temporal area of 21 patients, the extratemporal area of 29 patients. Of the patients who exhibited FDG-PET hypometabolism (PET-positive), 23 were classified as temporal, 17 as frontal, 11 showed involvement of the posterior cortex. The age of seizure onset was younger in PET-positive patients (p=0.032), and histopathological analyses revealed that 23 patients had type I FCD and 30 patients had type II FCD., Conclusion: PET scans reveal a lesion by showing hypometabolism in patients who have refractory epilepsy and an early age of onset with FCD. The lesions of MRI-negative/PET-positive FCD patients tend to be localized in the temporal lobe and that FCD may be localized in the frontal lobe of MRI-negative/PET-negative patients. However, the histopathological examinations of MRI-positive/PET-positive, MRI-negative/PET-positive, and MRI-negative/PET-negative patients did not exhibit a particular histopathological subtype., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy, a common chronic neurological disorder. Recent research that has expanded the knowledge of the cellular and molecular mechanisms that modulate neuronal excitability and network activity in the brain provides the development and discovery of antiepileptic drugs (AEDs). AED therapy starts with the selection of the most appropriate drug for individual patient according to a strategic decision based on the risk-benefit ratio. Beyond three generations of AEDs developed over the last 40 years, more effective, better tolerated, disease-modifying pharmacological therapies are still needed to improve seizure outcome and reduce the safety burden. In this review, we aim to provide a special focus on epilepsy with an overview of underlying pathophysiological mechanisms that may contribute to seizure generation and propagation. Besides, knowledge of principle pharmacological properties of current AEDs which are essential for rational drug therapy is considered. Limited safety data are available especially for recent AEDs, we also discussed their safety profiles concerning major adverse effects, teratogenicity and their use in pregnancy and lactation. Epilepsy is a chronic disorder which needs special knowledge and experience during AED treatment with meticulous follow-up of patients to avoid short and long-term adverse effects with the best possible seizure controlled outcome and high quality of life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Simultaneous central nervous system (CNS) infection with Cryptococcus and tuberculosis (TB) is very rare. Despite improved therapeutic options, treatment of CNS cryptococcosis is still difficult and needs invasive treatment modalities, such as intrathecal or intraventricular amphotericin B, in refractory cases. We describe a patient with systemic lupus erythematosus diagnosed with simultaneous cryptococcal and TB meningitis who had a poor response to intravenous liposomal amphotericin B and fluconazole, but was successfully treated with intraventricular amphotericin B, in addition to anti-TB therapy., (Copyright © 2013. Published by Elsevier B.V.)

Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). We have investigated CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3 allelic variants in a Turkish population of patients on phenytoin therapy. Patients on phenytoin therapy (n = 102) for the prevention of epileptic seizures were included. Polymorphic alleles were analyzed by restriction fragment length polymorphism method. Serum concentrations of phenytoin were measured by fluorescence polarization immune assay method. The most frequent genotype was detected for CYP2C9 wild-type alleles (78.43 %), whereas CYP2C19*2/*2 (5.88 %) was the least frequent genotype group. According to the classification made with both enzyme polymorphisms, CYP2C9*1/*1-CYP2C19*1/*1 (G1: 41.17 %) genotype group was the most frequent whereas CYP2C9*1/*2-CYP2C19*1/*3 (G7: 0.98 %) was the least frequent one. The highest mean phenytoin level (27.95 ± 1.85 µg/ml) was detected in the G8 genotype group (CYP2C9*1/*3-CYP2C19*2/*3) and the G1 genotype group showed the lowest mean phenytoin level (7.43 ± 0.73 µg/ml). The mean serum concentration of phenytoin of the polymorphic patients with epilepsy was higher than that for the wild-type alleles both in the monotherapy and polytherapy patients. These results show the importance of the genetic polymorphism analysis of the main metabolizing enzyme groups of phenytoin for the dose adjustment.

Aim: Surgery is a treatment option for medically intractable epilepsy patients. Abnormalities in regional cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have predictive prognostic value in evaluating the outcome of epilepsy surgery. This study investigated the efficacy of FDG-PET for delineation of the epileptogenic zone (EZ) by comparing its consistency with other diagnostic tools and surgical outcome., Material and Methods: We analyzed the results of 121 consecutive patients evaluated for epilepsy surgery. FDG-PET results were crosschecked with magnetic resonance imaging (MRI) and electroencephalography (EEG) results, as well as postoperative outcome and pathology., Results: FDG-PET findings of 75 patients (62 %) were concordant with MRI (Mc-Nemar-χ2 test p=0.024, Kappa=0.22). Further, the PET findings were consistent with EEG, and was statistically significant, according to Post-hoc test, in temporal epilepsy (TLE) group (χ2=8.21 P=0.04). Both investigations revealed localizing information in 56 (46.2%) patients. Twenty-six (72.2%) MRI-negative patients had hypometabolism on PET. The pathology of the 10 PET-negative patients was 5 cases of mesial temporal sclerosis, 2 cortical dysplasia, 2 gliosis and one tumor. Seven (70%) of these patients' lesions originated from the temporal lobe. FDG-PET had correctly predicted the EZ in 37 (86%) of 43 patients who underwent surgery., Conclusion: FDG-PET results may not be strongly associated with EZ but represent an additional tool in delineation of EZ during the noninvasive phase of presurgical evaluation.

Aim: Surgery for epilepsy is a significant treatment alternative with favorable outcomes in the pediatric age group. In this study we present the surgical outcomes of pediatric population referred to our center., Material and Methods: The clinical data of 126 patients (≤18 years) with lesional partial epilepsies operated in our center between 1995- 2011 were evaluated retrospectively. Parameters investigated were gender, age at seizure onset, duration of epilepsy, etiology, type and location of operation and outcome. Seizure outcome was classified according to Engel's classification., Results: The study group consisted of 70 males (55,6%) and 56 females (44.4%). The most common etiology was malformation of cortical development followed by tumors and hippocampal sclerosis. Overall 73.8% of patients had Engel I, 13.5% Engel II and 11.9% Engel III+IV postoperative seizure outcome., Conclusion: The results of our pediatric patients who underwent surgery were similar to previous reports in the literature. The seriousness of the clinical picture should tempt physicians to refer the patients as soon as possible to avoid long term complications like epileptic encephalopathies and the side effects of antiepileptic drugs during the development of the young brains.

Aim: Awake craniotomy (AC) with electrical cortical stimulation has become popular during the last ten years although the basic principles were introduced almost 50 years ago. The aim of this paper is to share with the readers our experience in 25 patients who underwent AC with electrical stimulation., Material and Methods: Twenty-five patients who underwent AC between 2010 and 2013 are the subjects of this paper. All patients were diagnosed with intraaxial lesions involving the functional area itself or very close to it by preoperative imaging. During surgery, the functional area was demonstrated by cortical electrical stimulation and resection aimed to preserve it in order to avoid an irreversible functional deficit., Results: Total resection was possible in 80% while in 20% subtotal resection had to be performed because of involvement of the functional area itself. The neurological complication rate was found to be 16% (4 patients) and all were transient. No complication regarding anesthesia was noted., Conclusion: Awake craniotomy in selected patients is very effective, safe and practical for supratentorial lesions close to the eloquent area. Complications related to the surgery itself are uncommon and general anesthesia is avoided. The hospital stay including the intensive care unit is short which makes it very economical surgical procedure.

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity.

Low-grade gliomas (LGGs) are generally located in temporal lobe and cause medically-intractable seizure so that surgical treatment becomes inevitable. This study includes a retrospective analysis of our patients with temporal LGGs retrieved from our epilepsy surgery data base and tries to present appropriate surgical approach and long-term seizure and anti-epileptic drug (AED) outcomes. Fifty-three patients including children and adults underwent surgery on temporal lobe LGGs and 35 patients were reached to report seizure and AED outcomes. On the non-dominant temporal lobe, anterior temporal resection with hippocampectomy whether mesial structure are involved or not is the appropriate approach. On the dominant temporal lobe mesial structures should be respected. However, total resection of the tumor should be the goal of surgery. Mean follow-up period was 8.3 years and favorable seizure outcome was found to be 91.4%. Surgery decreased AED usage and mean number of AED significantly decreased. Children also benefited from surgery as adults. Surgical treatment of tumor-related epilepsy from temporal lobe controls seizures, and total removal should be the main goal of surgery as neuropsychological testing permit., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Epilepsy is relatively uncommon in patients with Neurofibromatosis Type 1 (NF1) and seizures are usually well controlled with antiepileptic treatment. However, pharmacoresistance has been reported in patients with NF1 and MRI evidence of malformations of cortical development or glioneuronal tumours. Available information on epilepsy surgery in NF1 is limited to a few patients with gliomas and glioneuronal tumours who underwent lesionectomies. We conducted a survey amongst 25 European epilepsy surgery centres to collect patients with NF1 who had undergone surgery for drug-resistant seizures and identified 12 patients from eight centres. MRI abnormalities were present in all patients but one. They were unilateral temporal in eight, bilateral temporal in one and multilobar or hemispheric in two. Seizures originated from the temporal lobe in ten patients, from the temporo-parieto-occipital region in one, and were bitemporal in one. One year after surgery eight patients were seizure free, one had worthwhile improvement and the remaining three had experienced no benefit. Postoperative outcome, available at 2 years in ten patients and at 5 years in three, remained stable in all but one whose seizures reappeared. Histology revealed dysembryoplastic neuroepithelial tumour (DNET) in five patients, hippocampal sclerosis in four, mixed pathology in one and polymicrogyria in one. No histological abnormality was observed in the remaining patient. Epilepsy surgery can be performed effectively in patients with NF1 provided a single and well-delimited epileptogenic zone is recognized. The high prevalence of DNETs in this series might suggest a non-fortuitous association with NF1., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Although there have been a number of psychotherapy trials for chronic psychogenic nonepileptic seizures, evidence-based treatment options are limited. We developed an eclectic group psychotherapy which combines psychoeducation and behavioral and psychoanalytic techniques. Nine patients completed 12 weeks of psychotherapy. Patients were interviewed with SCID-I. They also filled in the following measures at the beginning and end of the therapy: Beck Depression Inventory, Dissociative Experiences Scale, Spielberger State-Trait Anxiety Scale, SF-36 Life Quality Scale, and Toronto Alexithymia Scale. Seizure frequency was assessed before and after the therapy and on follow-up visits at the fourth, sixth, ninth, and twelfth months. After one year of follow-up, the decrease in seizure frequency was highly significant (p<0.001). In addition, we observed significant improvements in the mental health subscale of the SF-36 (p=0.03) and the state (p=0.006) and trait (p=0.02) subscales of the Spielberger State-Trait Anxiety Scale at the end of the therapy. These results suggest that group psychotherapy might be a treatment option for chronic psychogenic nonepileptic seizures., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1(GLU7ALA)), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1(GLU7ALA), compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1(GLU7ALA) relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system.

The purpose of this cross-sectional study was to explore the attitudes of individuals with epilepsy (IWE) toward their condition via self-reported changes in the feelings/thoughts about having epilepsy. We aimed to investigate whether individuals with epilepsy perceive a change in their initial attitudes toward the condition over time. Additionally, if a change was perceived, the variables which predict the current thoughts/feelings toward epilepsy were also examined. Seventy adult IWE participated in the study. Of the 70 participants in the study, 25.7% retained their initial feelings/thoughts without any change. Among the IWE who reported no-change, the most common category was "negative from the beginning". On the other hand, 74.3% of the participants reported a change. Of the 74.3% of participants reporting change, the most common direction was from negative to positive" (79.2%) seeming to indicate a positive adjustment over the passage of time. In a logistic regression, only three factors were found to predict positive feelings/thoughts toward epilepsy: a clear understanding of the condition, low levels of depression and current employment status. Finally, there is a discussion of the potential applications of the IWE' self-assessment of their attitudes., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Hippocampal sclerosis (HS) is the most frequent cause of drug-resistant focal epilepsies (ie, mesial temporal lobe epilepsy with hippocampal sclerosis; mTLE-HS), and presents a broad spectrum of electroclinical, structural and molecular pathology patterns. Many patients become drug resistant during the course of the disease, and surgical treatment was proven helpful to achieve seizure control. Hence, up to 40% of patients suffer from early or late surgical failures. Different patterns of hippocampal cell loss, involvement of other mesial temporal structures, as well as temporal neocortex including focal cortical dysplasia, may contribute to the extent of the epileptogenic network and will be discussed. An international consensus is mandatory to clarify terminology use and to reliably distinguish mTLE-HS subtypes. High-resolution imaging with confirmed histopathologic diagnosis, as well as advanced neurophysiologic and molecular genetic measures, will be a powerful tool in the future to address these issues and help to predict each patient's probability to control their epilepsy in mTLE-HS conditions., (© 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.)

This study aimed to show the difference of epilepsy from another chronic neurological disorder with episodic manifestations (CDEM): migraine. Seventy persons with epilepsy (PWE), 56 persons with migraine (PWM) and 45 healthy control participants (HCs) were included. The groups were compared in terms of demographics, quality of life, depression and self-esteem. The PWE and PWM were also compared with regard to stigma, impact of the illness, disclosure, application of spiritual/traditional healing methods, limitations, most affected life areas, and restrictions. Results showed that the PWM had lower quality of life values than the PWE and the HCs, while there was no difference among the groups in depression and self-esteem. Results also show higher unemployment levels and lower marriage rates for the PWE, where education levels were equal. Although the PWM had higher impact of illness values, the PWE were shown to have higher stigma, more concealment behavior, and higher traditional/spiritual healing application ratios. Also, the PWM emphasized the importance of being "able to fulfil daily living, social and work activities", while the PWE emphasized the need for "independence" constantly. These results indicate that, although both migraine and epilepsy are CDEMs, they have different levels of impact on patients' lives. The impacts are socially greater in epilepsy and extend beyond the neurological condition itself., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Lamotrigine (LTG) which has a widespread use in epilepsy treatment as an antiepileptic agent is metabolized by UDP-glucuronosyl transferase (UGT) enzymes. In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels of LTG of wild type and polymorphic subjects. High performance liquid chromatography (HPLC) was used to measure serum concentrations of LTG. The P24T and L48V polymorphisms of the UGT1A4 enzyme were analyzed with a matrix assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry method. The frequencies of the heterozygous alleles for L48V or P24T polymorphisms were 22.4% and 3.8%, respectively. L48V polymorphism was found to decrease the serum concentration of LTG in patients on monotherapy or polytherapy. The LTG levels of non smoking monotherapy patients were 52% lower for the L48V polymorphism than for wild type alleles. Also the LTG levels were significantly lower for non smoking or smoking polymorphic alleles than for normal. The high frequency of the L48V polymorphism detected in the Turkish population indicates that LTG dose adjustments in patients with the UGT1A4 L48V polymorphic enzyme should be taken into account., (Copyright © 2011 Elsevier B.V. All rights reserved.)