Effectiveness and Safety of Epilepsy Surgery for Pediatric Patients with Intractable Epilepsy: A Clinical Retrospective Study from a Single-Center Experience.

INTRODUCTION: Pediatric epilepsy surgery is an effective treatment modality for patients with drug-resistant epilepsy (DRE). Early pediatric surgery yields favorable results for DRE in terms of seizure control and neurophysiological outcome. In this study, pediatric patients were categorized based on their age (above 3 years old and below 3 years old) to demonstrate the effectiveness and safety of surgical procedures. METHODS: In this retrospective, single-center study, 60 pediatric patients who underwent epilepsy surgery at Istanbul Faculty of Medicine between 2002 and 2018 were evaluated. Overall morbidity and mortality rates, as well as seizure outcomes of the patients, were assessed and compared based on two age groups: those aged 3 years old or younger and those older than 3 years old. The effectiveness of invasive monitoring was also evaluated in relation to pathological results. The postoperative seizure outcome rates were evaluated using Engel's classification, with an average follow-up period of 8.7 years. RESULTS: Out of the total number of patients, 47 (78.4%) underwent resective surgery, while 13 (21.6%) had palliative surgery. Ten patients (16.6%) had invasive monitoring. Among all patients, 34 were classified as Engel I and II (56.6%), while 26 were classified as Engel III and IV (43.4%) postoperatively. 47% of patients who were under 3 years old, 60.4% of patients who were over 3 years old, and 50% of patients who underwent invasive monitoring had a favorable seizure outcome (Engel I-II). Postoperative morbidity and mortality rates were 35% (n = 21) and 1.6% (n = 1), respectively. CONCLUSION: Pediatric epilepsy surgery is an important treatment modality for preserving cognitive abilities and providing effective treatment for pediatric DRE. In our study, we claim that both invasive monitoring and epilepsy surgery lead to favorable seizure outcomes for all age groups. Further clinical studies should be conducted to provide more reliable data on the safety and effectiveness of the surgery, particularly in patients under the age of three.

Efficacy and tolerability of immediate switch from sodium channel blockers to Lacosamide.

Lacosamide (LCM) is a new-generation anti-seizure medication approved for monotherapy and add-on therapy for focal-onset epilepsy. It has novel pharmacodynamics and favorable pharmacokinetic qualities with good clinical response. This study aims to evaluate the effectiveness and tolerability of LCM when used in the immediate switch from sodium channel blockers in patients with focal-onset and generalized-onset epilepsies. This retrospective, multicenter observational study was conducted with adult patients who received LCM as mono- or polytherapy through immediate switch with 6 to 52 months follow-up. The clinical data obtained during the follow-up period were analyzed to assess retention rate, seizure freedom, more than 50% seizure reduction, and adverse effects. A total of 32 patients (eight females, 24 males) with a median age of 49.75 (range, 23-86) years, median age at epilepsy onset of 32.58 (range, 0.5-85) years, and median epilepsy duration of 17.17 (range, 1-46) years were included in this study. Seizure frequency was between 1 and 90 in the past 6 months. Seven (21.9%) of the patients had structural brain lesions and 27 (84.4%) of the patients had EEG abnormalities. The adverse effects leading to switching were hyponatremia, rash, elevated liver enzymes, pain, and erectile dysfunction. At 14.34 (range, 6-52) months follow-up, 30 (93.75%) patients in total retained LCM, 20 (66.7%) of them were seizure-free, and 13 were on LCM monotherapy. Responder rate was 81.25%. Eight (25%) of the patients experienced adverse effects after the immediate switch. One patient with generalized-onset epilepsy needed to quit LCM due to an increase in seizures. Seizure frequency did not change in three patients in the focal-onset group. Immediate switch to LCM showed favorable outcomes with a significant reduction in seizure frequency, high retention rates, and tolerable adverse effect profiles in both focal-onset and generalized-onset seizures.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

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.

Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis.

OBJECTIVE: In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies. METHODS: Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation. RESULTS: In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases. CONCLUSIONS: Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.

Elimination of pseudo-HFOs in iEEG using sparse representation and Random Forest classifier.

High-Frequency Oscillation (HFO) is a promising biomarker of the epileptogenic zone. However, sharp artifacts might easily pass the conventional HFO detectors as real HFOs and reduce the seizure onset zone (SOZ) localization. We hypothesize that, unlike pseudo-HFOs, which originates from artifacts with sharp changes or arbitrary waveform characteristic, real HFOs could be represented by a limited number of oscillatory waveforms. Accordingly, to distinguish true ones from pseudo-HFOs, we established a new classification method based on sparse representation of candidate events that passed an initial detector with high sensitivity but low specificity. Specifically, using the Orthogonal Matching Pursuit (OMP) and a redundant Gabor dictionary, each event was represented sparsely in an iterative fashion. The approximation error was estimated over 30 iterations which were concatenated to form a 30-dimensional feature vector and fed to a random forest classifier. Based on the selected dictionary elements, our method can further classify HFOs into Ripples (R) and Fast Ripples (FR). In this scheme, two experts visually inspected 2075 events captured in iEEG recordings from 5 different subjects and labeled them as true-HFO or Pseudo-HFO. We reached 90.22% classification accuracy in labeled events and a 21.16% SOZ localization improvement compared to the conventional amplitude-threshold-based detector. Our sparse representation framework also classified the detected HFOs into R and FR subcategories. We reached 91.24% SOZ accuracy with the detected [Formula: see text] events. Clinical Relevance---This sparse representation framework establishes a new approach to distinguish real from pseudo-HFOs in prolonged iEEG recordings. It also provides reliable SOZ identification without the selection of artifact-free segments.

A sparse representation strategy to eliminate pseudo-HFO events from intracranial EEG for seizure onset zone localization.

Objective.High-frequency oscillations (HFOs) are considered a biomarker of the epileptogenic zone in intracranial EEG recordings. However, automated HFO detectors confound true oscillations with spurious events caused by the presence of artifacts.Approach.We hypothesized that, unlike pseudo-HFOs with sharp transients or arbitrary shapes, real HFOs have a signal characteristic that can be represented using a small number of oscillatory bases. Based on this hypothesis using a sparse representation framework, this study introduces a new classification approach to distinguish true HFOs from the pseudo-events that mislead seizure onset zone (SOZ) localization. Moreover, we further classified the HFOs into ripples and fast ripples by introducing an adaptive reconstruction scheme using sparse representation. By visualizing the raw waveforms and time-frequency representation of events recorded from 16 patients, three experts labeled 6400 candidate events that passed an initial amplitude-threshold-based HFO detector. We formed a redundant analytical multiscale dictionary built from smooth oscillatory Gabor atoms and represented each event with orthogonal matching pursuit by using a small number of dictionary elements. We used the approximation error and residual signal at each iteration to extract features that can distinguish the HFOs from any type of artifact regardless of their corresponding source. We validated our model on sixteen subjects with thirty minutes of continuous interictal intracranial EEG recording from each.Main results.We showed that the accuracy of SOZ detection after applying our method was significantly improved. In particular, we achieved a 96.65% classification accuracy in labeled events and a 17.57% improvement in SOZ detection on continuous data. Our sparse representation framework can also distinguish between ripples and fast ripples.Significance.We show that by using a sparse representation approach we can remove the pseudo-HFOs from the pool of events and improve the reliability of detected HFOs in large data sets and minimize manual artifact elimination.

Blood-brain barrier targeted delivery of lacosamide-conjugated gold nanoparticles: Improving outcomes in absence seizures.

OBJECTIVE: Most currently available antiepileptics are not fully effective in the prevention of seizures in absence epilepsy owing to the presence of blood-brain barrier (BBB). We aimed to test whether binding an antiepileptic drug, lacosamide (LCM), to glucose-coated gold nanoparticles (GNPs) enables efficient brain drug delivery to suppress the epileptic activity in WAG/Rij rats with absence epilepsy. METHODS: In these animals, intracranial-EEG recording, behavioral test, in vivo imaging of LCM and LCM-GNP conjugate distribution in the brain, inductively coupled plasma mass spectrometry analysis, immunofluorescence staining of glucose transporter (Glut)- 1, glial fibrillary acidic protein (GFAP), and p-glycoprotein (P-gp) and electron microscopy were performed. RESULTS: Lacosamide-GNP conjugates decreased the amplitude and frequency of spike-wave-like discharges (SWDs) and alleviated the anxiety-like behavior as assessed by EEG and elevated plus-maze test, respectively (p < 0.01). The in vivo imaging system results showed higher levels of fluorescein dye tagged to LCM-GNP in the brain during the 5-day injection period (p < 0.01). Immunofluorescence staining displayed decreased P-gp, Glut-1, and GFAP expression by LCM-GNP conjugate treatment predominantly in the cerebral cortex suggesting a potential functionality of this brain region in the modulation of neuronal activity in our experimental setting (p < 0.01). SIGNIFICANCE: We suggest that the conjugation of LCM to GNPs may provide a novel approach for efficient brain drug delivery in light of the effectiveness of our strategy not only in suppressing the seizure activity but also in decreasing the need to use high dosages of the antiepileptics to reduce the frequently encountered side effects in drug-resistant epilepsy.

An Investigation into the Correlation of Scalp Electrophysiological Findings with Preoperative Clinical and Imaging Findings in Patients with Focal Cortical Dysplasia.

AIM: To evaluate the patients who had epilepsy surgery and pathologically proven focal cortical dysplasia (FCD) in order to further classify and discuss electroencephalography (EEG) findings in different pathological subtypes. MATERIAL AND METHODS: This study included 19 refractory epilepsy patients who underwent surgery between 1999 and 2017 in the Istanbul Faculty of Medicine. Demographic data, preoperative examinations, scalp video EEGs, and postoperative outcomes were evaluated retrospectively. RESULTS: In this study, 36.8% of the patients were female. The mean age was 21.89 ± 14.64 years. Rhythmic epileptiform discharges (RED) were observed in 31.6%. 37.5% of the patients with isolated intermittent spike/sharp waves were type I, 50% were type II, and 12.5% were type III. 100% of the patients with normal background activity were FCD type II. 67% of the patients with asymmetric slowing were FCD type I, 22% was FCD type II, 11% were FCD type III. 71% of the patients with symmetrical slowing were FCD type I, 29% were FCD type II. One patient had Frontal Intermittent Rhythmic Activity, one patient had Electrical Status Epilepticus in Slow Sleep, two patients had "burst suppression," and one patient had a "switch of" sign. The frequency of focal epileptogenic activity was higher when there was an FCD lesion on magnetic resonance imaging. CONCLUSION: The findings obtained in this study did not reveal any distinctive electrophysiological features in FCD and subgroups of FCD. The incidence of REDs did not differ between types. The frequency of isolated intermittent sharp/spike waves was higher in type II than I. Intermittent and continuous EEG slowing was more commonly seen among FCD Type I patients.

Surgical Treatment in Refractory Epilepsy: Seizure Outcome Results Based on Invasive EEG Monitorization.

AIM: To discuss seizure outcomes of patients with invasive electroencephalography (EEG) monitorization (IEM) following their epilepsy surgery at our centre. MATERIAL AND METHODS: Forty-seven patients suffering from refractory epilepsy and who were evaluated by invasive EEG were included in this retrospective study at Istanbul Faculty of Medicine from 2003 to 2017. We examined the Video EEG and invasive EEG monitorization, cranial MRI, SPECT, PET and neuropsychological tests of all patients. Postoperative seizure outcome results were evaluated according to Engel classification. The factors affecting seizure outcomes were discussed. RESULTS: Twenty-six of the patients were female (55.3%), 21 were male (44.7). The average age was 32.0 (± 12.4). Forty-three patients had surgery and the average age of these patients was 26,6 (±11.15). 38.3% of the patients had hippocampal sclerosis (HS), 23.4% had focal cortical dysplasia (FCD), 8.5% had a tumor, 14.9% had sequela lesion and 14.9% had unknown etiology. Postoperative seizure status according to the Engel classification showed that 81.6% of the patients were class I, 10.5% were class II, 2.6% were class III and 5.3% were class IV. CONCLUSION: A significant relation was statistically determined between structural MRI lesion and favorable seizure outcome (p < 0.05). The most frequent etiology was HS in our patients. Of the patients with Engel I, the averages of their ages, ages at onset of epilepsy and ages at surgery were lower than other groups, but the difference was not statistically significant (p > 0.05). We argue that IEM is an essential examination for favorable outcomes for determining the epileptogenic zone and/or the proximity of the functional structures.

The effect of a seminar on medical students' information acquisition of and attitudes toward epilepsy.

AIM: The aim of the present study was to investigate the effect of a brief seminar focusing on medical and social aspects of epilepsy on information acquisition of and attitudes toward epilepsy among medical school students. METHOD: The sample of this pretest-posttest study consisted of 57 fifth-grade medical students. The students participated in a one-hour seminar including medical and social aspects of epilepsy. An epilepsy-related awareness form developed by researchers and also the Epilepsy Attitude Scale were applied to the participants before and after the seminar. RESULTS: It was determined that half of the students (50.9%) encountered an epileptic seizure and 12.3% of them applied first aid. The students had difficulty in describing the seizure type before education. Before education, the rate of describing the seizure was 47.4% for myoclonic seizure, 50.9% for simple partial seizure, and 64.9% for absence seizure, and after education, these rates increased to 82.5% (p < 0.001), 91.2% (p < 0.001), and 98.2% (p < 0.001), respectively. Students generally well described the seizure triggering factors; however, the rate of students reporting the menstrual period as triggering factors were lower (66.7%), and the rates increased after the education (93.0%) (p = 0.001). The percentages of correct answers increased also for the questions regarding seizure first aid. The percentage of students who felt competent for seizure first-aid management increased from 12.3% to 91.2% (p < 0.001) after the education. The correct response rates of students for social aspects of epilepsy was generally high. In our study, attitude toward epilepsy was also evaluated. After the education, a mild increase in the attitude score of students was found (p = 0.009). Although it is minimal, the number of students who marked more positive attitude increased for each item of the Attitude scale. CONCLUSION: Although a lack of acquaintance was found in some areas, awareness of epilepsy in our sample was at a moderate level. This study showed a positive effect of the education given to students on information acquisition and attitude.

Immune alterations in subacute sclerosing panencephalitis reflect an incompetent response to eliminate the measles virus.

In subacute sclerosing panencephalitis (SSPE) the persistence of measles virus (MeV) may be related to the altered immune response. In this study, cytokine responses of lymphocytes and monocytes were evaluated in SSPE compared to controls with non-inflammatory (NICON) and inflammatory (ICON) diseases. Patients with SSPE (n = 120), 78 patients with ICON and 63 patients with NICON were included in this study. Phenotypes of peripheral blood mononuclear cells (PBMC) have been analyzed by flow cytometry. CD3 and CD28, and S. aureus Cowan strain I (SAC) stimulated and unstimulated cells were cultured and IL-2, IL-10, IFN-γ, IL-12p40, IL-12p70 and IL-23 were detected in supernatants by ELISA. MeV peptides were used for MeV-specific stimulation and IFN-γ secretion of PBMC was measured by ELISPOT. Spontaneous and stimulated secretions of IL-10 were lower in SSPE compared to both control groups. T cell stimulation induced lower IFN-γ production than ICON group, but higher IL-2 than NICON group in SSPE. Stimulated PBMC produced lower IL-12p70 in SSPE and had decreased CD46 on the cell surface, suggesting the interaction with the virus. IFN-γ responses against MeV peptides were not prominent and similar to NICON patients. The immune response did not reveal an inflammatory activity to eliminate the virus in SSPE patients. Even IL-10 production was diminished implicating that the response is self-limited in controlling the disease.

Depression is a major determinant of sleep abnormalities in patients with epilepsy.

INTRODUCTION: We aimed to identify sleep disorders in patients with epilepsy and compare this group with a healthy population. We also analyzed the features of sleep disorders in patients with epilepsy to demonstrate the effect of seizures and seizure types on sleep. METHODS: Our study assessed 43 patients with epilepsy and 53 age- and gender-matched healthy controls. The demographic and clinical data of all participants were recorded. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), International Restless Legs Syndrome Study Group Rating Scale, Berlin Questionnaire, and Beck Depression Inventory (BDI) were administered to all study subjects. The interview used to evaluate insomnia is based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition - DSM-5 diagnostic criteria. RESULTS: Twenty-four patients (55.8%) and 26 controls (49.1%) are women. The mean age of patients and controls was 34.2±11.37 (16-71) and 34.6±11.28 (16-77), respectively. Patients with epilepsy had depression more often than controls, a result that was statistically significant (p<0.0001). We found no statistically significant difference between sleep parameters of patients and controls with normal BDI scores (p>0.05). Patients with depression had worse results on the Berlin Questionnaire and PSQI total score, with statistical significance (p=0.002). Nocturnal seizures, seizure type, and drug treatment had no effect on sleep (p>0.05). CONCLUSION: We concluded that depression rather than epilepsy negatively affects sleep, suggesting that all patients should be asked about their mood and sleep complaints.

Depression is a major determinant of sleep abnormalities in patients with epilepsy / A depressão é um dos principais determinantes das anormalidades do sono em pacientes com epilepsia

ABSTRACT Introduction: We aimed to identify sleep disorders in patients with epilepsy and compare this group with a healthy population. We also analyzed the features of sleep disorders in patients with epilepsy to demonstrate the effect of seizures and seizure types on sleep. Methods: Our study assessed 43 patients with epilepsy and 53 age- and gender-matched healthy controls. The demographic and clinical data of all participants were recorded. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), International Restless Legs Syndrome Study Group Rating Scale, Berlin Questionnaire, and Beck Depression Inventory (BDI) were administered to all study subjects. The interview used to evaluate insomnia is based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition - DSM-5 diagnostic criteria. Results: Twenty-four patients (55.8%) and 26 controls (49.1%) are women. The mean age of patients and controls was 34.2±11.37 (16-71) and 34.6±11.28 (16-77), respectively. Patients with epilepsy had depression more often than controls, a result that was statistically significant (p<0.0001). We found no statistically significant difference between sleep parameters of patients and controls with normal BDI scores (p>0.05). Patients with depression had worse results on the Berlin Questionnaire and PSQI total score, with statistical significance (p=0.002). Nocturnal seizures, seizure type, and drug treatment had no effect on sleep (p>0.05). Conclusion: We concluded that depression rather than epilepsy negatively affects sleep, suggesting that all patients should be asked about their mood and sleep complaints.

RESUMO Introdução: O objetivo deste estudo foi identificar distúrbios do sono em pacientes com epilepsia e compará-los com uma população saudável. Também foram examinadas as características dos distúrbios do sono em pacientes com epilepsia para demonstrar o efeito e os tipos de convulsões no sono. Métodos: O estudo consistiu em 43 pacientes com epilepsia e 53 controles saudáveis ​​pareados por idade e sexo. Os dados demográficos e clínicos de todos os participantes foram registrados. Todos os participantes do estudo receberam a Escala de Sonolência de Epworth, o Índice de Qualidade do Sono de Pittsburgh (Pittsburch Sleep QUality Index - PSQI), o Questionário do Grupo Internacional de Estudos das Pernas Inquietas, o Questionário de Berlim e o Inventário de Depressão de Beck. A entrevista usada para avaliar a insônia é baseada nos critérios do DSM-V. Resultados: Vinte e quatro pacientes (55,8%) são do sexo feminino e vinte e seis do grupo controle (49,1%) são do sexo feminino. A média de idade dos pacientes e do grupo controle é de 34,2±11,37 (16-71) e 34,6±11,28 (16-77), respectivamente. Pacientes com epilepsia sofrem mais de depressão do que os controles e esse resultado é estatisticamente significativo (p<0,0001). Não houve diferença estatisticamente significativa entre os parâmetros do sono dos pacientes e dos controles que apresentaram escores de Beck normais (p>0,05). Pacientes com depressão apresentam resultados piores no escore total do PSQI de Berlim, o que é estatisticamente significativo (p=0,002). As convulsões noturnas, o tipo de convulsão e o tratamento medicamentoso não afetaram o sono (p>0,05). Conclusão: Determinamos que a depressão, e não a epilepsia, afeta negativamente o sono dos pacientes, sugerindo que todos os pacientes devem ser questionados sobre seu humor e queixas de sono.

Functional connectivity analysis of patients with temporal lobe epilepsy displaying different ictal propagation patterns.

The pathophysiology of switch-of lateralization and bilateral temporal asynchrony, which are scalp EEG ictal propagation patterns (iPP) in temporal lobe epilepsy (TLE), is poorly understood. We aimed to analyse functional connectivity (FC) of the temporal lobe and related areas in patients with TLE with iPP (iPP-TLE) and without iPP (non-iPP TLE). Twelve patients with iPP-TLE, 13 patients with non-iPP TLE, and 13 healthy controls (HC) underwent resting-state functional MRI (fMRI). Seed-based FC was analysed between the homologous insulae, hippocampi, amygdalae, parahippocampal, superior temporal, and middle temporal gyri. FC was reduced between homologous temporal lobe areas in patients with TLE compared with HCs. Patients with non-iPP TLE displayed decreased FC between the homologous parahippocampal and superior temporal gyri, and patients with iPP-TLE had lower FC between the homologous insulae, parahippocampal and superior temporal gyri compared with HC. Furthermore, patients with iPP-TLE tended to have lower FC between the bilateral insulae when compared with patients with non-iPP TLE. Reduced FC of interhemispheric connections between temporal lobes and related areas might be an adaptive change to protect contralateral areas in seizure propagation. The insula showed decreased FC between two hemispheres in patients with iPP-TLE, assuming a role in ictal scalp propagation pattern changes in TLE.

Slow repetitive transcranial magnetic stimulation in refractory juvenile myoclonic epilepsies.

OBJECTIVE: The objective of the study was to investigate the effects of slow repetitive transcranial magnetic stimulation (rTMS) on patients with refractory juvenile myoclonic epilepsy (JME). METHODS: One thousand pulses with the intensity of 120% active motor threshold (AMT) at 0.2 Hz frequency were applied on 5 consecutive days in 10 patients with refractory JME. Sham rTMS was performed after 3 months. Electroencephalography (EEG) examinations were performed before rTMS, on the 5th day, and 1, 2, 4, and 8 weeks after rTMS. Resting motor threshold (RMT), AMT, and cortical silent periods (CSPs) were recorded before the application and at the end of day 5. The changes in the quality of life were evaluated using the Quality of Life in Epilepsy Inventory (QOLIE-31). RESULTS: No adverse effects were observed. The number of seizures decreased by 29-50%, and interictal discharge durations decreased 2 weeks after the real rTMS. No significant difference was observed between the AMT and RMT values recorded before and after the stimulations. Statistically significant increases in CSP duration and quality of life scores were found following real rTMS. Repetitive transcranial magnetic stimulation may be considered as a safe treatment option in refractory JME. CONCLUSION: This study provides some positive evidence that rTMS may be effective in resistant JME.

Targeted delivery of lacosamide-conjugated gold nanoparticles into the brain in temporal lobe epilepsy in rats.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures, and currently available drugs may fail to provide a thorough treatment of the patients. The present study demonstrates the utility of glucose-coated gold nanoparticles (GNPs) as selective carriers of an antiepileptic drug, lacosamide (LCM), in developing a strategy to cross the blood-brain barrier to overcome drug resistance. Intravenous administration of LCM-loaded GNPs to epileptic animals yielded significantly higher nanoparticle levels in the hippocampus compared to the nanoparticle administration to intact animals. The amplitude and frequency of EEG-waves in both ictal and interictal stages decreased significantly after LCM-GNP administration to animals with TLE, while a decrease in the number of seizures was also observed though statistically insignificant. In these animals, malondialdehyde was unaffected, and glutathione levels were lower in the hippocampus compared to sham. Ultrastructurally, LCM-GNPs were observed in the brain parenchyma after intravenous injection to animals with TLE. We conclude that glucose-coated GNPs can be efficient in transferring effective doses of LCM into the brain enabling elimination of the need to administer high doses of the drug, and hence, may represent a new approach in the treatment of drug-resistant TLE.

Relationship Between Sleep Characteristics and Sudden Unexplained Death Risk in Epilepsy.

BACKGROUND: Sleep disorders and disturbances are generally underestimated in patients with epilepsy. The aim of this study is to determine the frequency of sleep disturbances and the comorbidity of sleep disorders in people with epilepsy without any complaints about sleep and their relation of sudden unexplained death in epilepsy (SUDEP) risk. METHODS: Sleep complaints and the presence of sleep disorders were assessed with 4 questionnaires in 139 patients with epilepsy. Subjective sleep features were evaluated with Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Berlin Questionnaire for sleep apnea, and restless legs syndrome with International Restless Legs Syndrome Study Group (IRLSSG) severity scale. The presence of rapid eye movement/nonrapid eye movement parasomnia was asked to the patients and their relatives who share the same house. The patients' SUDEP-7 scores were also determined and associations with sleep problems were investigated statistically. RESULTS: Ninety-two patients with focal and 47 patients with generalized epilepsy were evaluated after their consent. The daily sleep quality was poor in 34 (24.5%) patients with PSQI. Daily sleepiness was present in 7 (5%) patients with ESS. Twenty-five patients (18%) had severe sleep apnea risk with the Berlin Questionnaire. Mild or severe RLS was detected in 24 patients (17.2%). There were no significant differences between focal or generalized epilepsy groups' scores. No statistically significant relationship was identified between SUDEP-7 scores and sleep quality or sleep-related disorders. CONCLUSION: Our results emphasized a remarkable magnitude of the comorbidity of sleep disorders in patients with epilepsy, even for those who do not have complaints about sleep. As SUDEP cases are frequently seen during sleep, it is important to evaluate sleep in patients with epilepsy.

The Impact of Affective State on Quality of Life in Focal Epilepsy in Turkey.

CONTEXT: Seizures and accompanying situations including social, medical, and psychiatric problems threaten the quality of life (QOL) in patients with epilepsy. The World Health Organization defines health is a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity. AIMS: This study examines the prevalence of both depression and anxiety symptoms and also impact of the affective state on QOL in patients with focal epilepsy in Turkey. SETTINGS AND DESIGN: One hundred and five patients with focal epilepsy over 18 years old were included in this study. The patients were classified into four groups according to the presence of AS and seizure control. SUBJECTS AND METHODS: Patients' affective symptoms (AS) and QOL were examined using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and QOL in Epilepsy Inventory-31 (QOLIE-31). STATISTICAL ANALYSIS USED: We used descriptive statistics, Chi-square test, independent samples t-test, one-way analysis of variance, Mann-Whitney U-test, Kruskal-Wallis H-test, and also Pearson's and Spearman's correlation test for correlations. RESULTS: There were positive correlations between total QOLIE-31 score and epilepsy surgery, employment, and seizure freedom, whereas negative correlations were found with antiepileptic drug use, anxiety, and depression. Statistically significant differences were found in QOLIE-31 totals and subscores between Groups 3 and 4 (P < 0.05). CONCLUSIONS: The presence of AS has a negative impact on QOL in patients with focal epilepsy. Physicians should be aware that psychiatric comorbidities in epilepsy have a severe impact and epilepsy treatment requires comprehensive management.