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.

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.

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.

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.

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.

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.

Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy.

High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001.

Impact of seizure-related injuries on quality of life.

OBJECTIVE: Our aim is to assess the types and frequency of seizure-related injuries and to determine their effects on Quality of Life (QoL). METHODS: Fifty-seven patients with epilepsy were included to our study. The demographic and clinical data of all the participants were recorded. All patients completed the Quality of Life in Epilepsy Inventory 89 (QOLIE-89). Injury types were classified as burns, head trauma, dental traumas, fractures, body injuries, penetrating traumas, road injuries, and drowning. RESULTS: Forty-two patients had seizure-related physical injury history whereas 15 of them declared no history of injury. Lower education levels and more frequent seizures were associated with higher seizure-related injury rates (p < 0.05). The most common types of seizure-related injuries were head trauma (22%) and fractures (17%). Fifty-seven (64%)of the injuries took place at home. There was no difference in QOLIE-89 scores between patients with or without seizure-related injury. Multiple injuries, admission to emergency, older than 20 years of the first seizure-related injury, and shorter than 10 years after last seizure-related injury are negatively effective on the QoL scores. CONCLUSION: Patients with epilepsy are likely to have seizure-related injuries which may be severe but do not affect the patients' QoL. Seizure-related injuries most commonly occur at home and therefore simple precautions (supervised bathing, using microwave ovens instead of classical stoves, avoiding electric irons and electric heaters, and sleeping close to the floor to avoid falling) taken to reduce the incidence of seizure-related injuries will help reduce hospitalizations and will also be cost-effective.

Clinical and electrophysiological findings in patients with phenylketonuria and epilepsy: Reflex features.

OBJECTIVE: Phenylketonuria (PKU) is the most common form of amino acid metabolism disorders with autosomal recessive inheritance. The brain damage can be prevented by early diagnosis and a phenylalanine-restricted diet. Untreated or late-treated patients may show mental retardation and other cognitive dysfunctions, as well as motor disability and/or epilepsy. METHODS: Three patients with PKU and epilepsy were recognized to have reflex epileptic features, and there were ten consecutive adult patients with PKU and epilepsy who were evaluated retrospectively. Medical history, ages at diagnosis and therapy onset, age at seizure onset, seizure types and reflex features, neurological findings, cranial imaging, electroencephalography (EEG) findings, and final clinical condition were evaluated. Reflex epilepsy features were examined in detail. RESULTS: The cases (6 females, 4 males) were diagnosed at ages between 3.5months and 12years. All patients had various degrees of mental-motor retardation and focal or generalized seizures with age at seizure onset varied between neonatal period and 15years. Three patients had febrile seizure, 3 patients had myoclonia, and 3 patients had status epilepticus. All patients had abnormal EEG findings except one. There was a slowing of background activity, and generalized discharges were observed in 7 patients; 3 of them had asymmetrical discharges. One patient had right hippocampal sclerosis (HS), and another patient had hypointensities in the basal ganglia and corpus callosum. Reflex features were clinically observed in 3 of the patients; however, EEG results did not show any related findings. One patient had reflex seizures triggered by photic stimuli, hot water, and startling; one by photic stimuli; and the other one by startling. CONCLUSION: Reports on the clinical and electrophysiological features of adult patients with PKU were scant. We emphasized that reflex clinical features may be observed in this metabolic disease, and focal epileptiform abnormalities and asymmetry may be present in electrophysiological evaluation besides the rare association with HS.

Unusual ictal propagation patterns suggesting poor prognosis after temporal lobe epilepsy surgery: Switch of lateralization and bilateral asynchrony.

OBJECTIVE: The objective of this study was to investigate unusual ictal propagation patterns in patients with drug-resistant temporal lobe epilepsy (TLE) and reveal their electrophysiological, neuroimaging, and prognostic properties after surgery. METHODS: Among 248 patients with TLE who underwent scalp video-electroencephalographic (EEG) monitoring, 24 patients with 'switch of lateralization' or 'bilateral asynchrony' in at least one of their seizures (9.3%) were analyzed retrospectively. The postoperative outcome was determined in 16 patients who had undergone epilepsy surgery. RESULTS: All but 5 of the included patients had hippocampal sclerosis (HS) as their magnetic resonance imaging (MRI) findings. Twelve out of 16 patients (75%) who had surgery were seizure-free for at least 1 year. Nine out of 12 patients (75%) with good outcome had unilateral interictal EEG discharges in temporal regions whereas 3 out of 4 patients with poor outcome had bilateral temporal interictal spiking (p = 0.018). CONCLUSION: Unusual ictal propagation patterns are not always related to poor prognosis after surgery in patients with TLE. Patients with unilateral interictal spiking in the temporal region tend to have good outcome despite these unusual patterns. These patterns can also be seen in patients with TLE with other etiologies besides the well-known HS in MRI.

Genital automatisms: Reappraisal of a remarkable but ignored symptom of focal seizures.

OBJECTIVES: Genital automatisms (GAs) are uncommon clinical phenomena of focal seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The aim of this study was to determine the lateralizing and localizing value and associated clinical characteristics of GAs. METHODS: Three hundred thirteen consecutive patients with drug-resistant seizures who were referred to our tertiary center for presurgical evaluation between 2009 and 2016 were investigated. The incidence of specific kinds of behavior, clinical semiology, associated symptoms/signs with corresponding ictal electroencephalography (EEG) findings, and their potential role in seizure localization and lateralization were evaluated. RESULTS: Fifteen (4.8%) of 313 patients had GAs. Genital automatisms were identified in 19 (16.4%) of a total 116 seizures. Genital automatisms were observed to occur more often in men than in women (M/F: 10/5). Nine of fifteen patients (60%) had temporal lobe epilepsy (right/left: 4/5) and three (20%) had frontal lobe epilepsy (right/left: 1/2), whereas the remaining two patients could not be classified. One patient was diagnosed as having Rasmussen encephalitis. Genital automatisms were ipsilateral to epileptic focus in 12 patients and contralateral in only one patient according to ictal-interictal EEG and neuroimaging findings. Epileptic focus could not be lateralized in the last 2 patients. Genital automatisms were associated with unilateral hand automatisms such as postictal nose wiping or manual automatisms in 13 (86.7%) of 15 and contralateral dystonia was seen in 6 patients. All patients had amnesia of the performance of GAs. CONCLUSION: Genital automatisms are more frequent in seizures originating from the temporal lobe, and they can also be seen in frontal lobe seizures. Genital automatisms seem to have a high lateralizing value to the ipsilateral hemisphere and are mostly concordant with other unilateral hand automatisms. Men exhibit GAs more often than women.

The Effects of Lipopolysaccharide on the Disrupted Blood-Brain Barrier in a Rat Model of Preeclampsia.

BACKGROUND: Preeclampsia is a disorder characterized by high blood pressure and often proteinuria during pregnancy. It is known that a subseptic dose of bacterial lipopolysaccharide (LPS) induces production of proinflammatory cytokines, and possibly increasing the risk for developing preeclampsia. We investigated the effects of LPS on the blood-brain barrier (BBB) integrity in pregnant rats with N(omega)-nitro-l-arginine methyl ester (L-NAME) induced preeclampsia. METHODS: Starting from the 10th day of gestation, pregnant rats were given L-NAME for 10 days to produce hypertension and proteinuria. Animals were then treated with a single injection of LPS on the 19th day of pregnancy. Arterial blood pressure and proteinuria were measured on the day of the experiment, which was 24 hours after the LPS injection. The BBB integrity was assessed by using Evans blue (EB) and horseradish peroxidase (HRP) tracers. RESULTS: Proteinuria was observed in varying degrees, and the arterial blood pressure increased in L-NAME-treated pregnant rats (P < .01). The overall brain EB content did not increase in these preeclamptic rats when compared to pregnant animals, and LPS treatment also did not change EB content. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in the capillary endothelial cells in the cerebral cortex and hippocampus of pregnant rats treated with L-NAME (P < .01). However, LPS did not change the amounts of HRP that mainly accumulated in brain capillary endothelial cells of these animals. CONCLUSION: Our results suggest that, in this experimental setting, LPS does not change the severity of BBB disruption observed in preeclamptic animals.

Predictors of outcomes and refractoriness in status epilepticus: A prospective study.

OBJECTIVE: The objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE). METHODS: This is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used. RESULTS: Logistic regression analysis showed that being aged ≥65years (p=0.02, OR: 17.68, 95% CI: [1.6-198.4]) for the short term and having potentially fatal etiology (p=0.027, OR: 11.7, 95% CI: [1.3-103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p=0.032, OR: 13.7, 95% CI: [1.3-148.5]). The patients with ≥3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p=0.157) and long term (p=0.065). There was no difference between patients with 0-2, 3-4, and ≥4 mSTESS in the short- and long term in terms of outcome (p=0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p=0.025 and 0.017, respectively). The patients with ≥64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p=0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p<0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥64 points in EMSE-EACE had significantly poorer outcome in the both short- and long term (p=0.014 and 0.012, respectively), and patients with CSE with ≥27 points in EMSE-EAC had significantly poorer outcome in the long term (p=0.03) but not in the short term (p=0.186). Outcomes did not correlate with EMSE scores in patients with NCSE and EPC. Status epilepticus was terminated with intravenous (IV) levetiracetam (LEV) in 68.75% of patients and with IV phenytoin (PHT) in 83.3% of patients. No statistically significant difference was found between the two groups in terms of efficacy (p=0.334). CONCLUSION: Being aged ≥65years predicts poor short-term outcomes, and having potentially fatal etiology predicts poor long-term outcomes, which highlight the importance of SE treatment management in the elderly. Both STESS and mSTESS are not predictive for poor outcomes in EPC. Excluding patients with EPC, STESS, and mSTESS could predict poor long-term outcomes but not in the short term in SE. Epidemiology-based Mortality in Status Epilepticus score could predict poor outcome in the long term better than STESS and mSTESS. Specifically, EMSE scores correlated with poor outcome in patients with CSE but not with NCSE and EPC. New scales are needed to predict outcome especially in patients with NCSE and EPC. The presence of PEDs in EEG is a predictor of RSE, and EMSE score can also be used to predict RSE. There was no difference in the efficacy of IV LEV and IV PHT in SE. This study is significant for having one of the longest follow-up periods in the literature.

Changes in electroencephalographic characteristics and blood-brain barrier permeability in WAG/Rij rats with cortical dysplasia.

PURPOSE: This study investigated the effects of cortical dysplasia (CD) on electrophysiology and blood-brain barrier (BBB) permeability in WAG/Rij rats with genetic absence epilepsy. METHODS: Pregnant WAG/Rij rats were exposed to 145cGy of gamma-irradiation on embryonic day 17 to induce CD. An electroencephalogram was recorded from cortices subdurally in the offspring of the pregnant animals. Horseradish peroxidase (HRP) was used as determinant of BBB permeability. RESULTS: A massive tissue loss in the cerebral cortex was seen in WAG/Rij rats with CD (p<0.05). There was a significant decrease in the number and duration of spike-and-wave discharges (SWDs) and an increase in the frequency of SWDs in the WAG/Rij rats with CD when compared with the properties of SWDs in intact WAG/Rij rats (p<0.01). Ultrastructurally, the accumulation of HRP reaction products in the cerebral cortex and thalamus of WAG/Rij rats was significantly higher than that of control values (p<0.01). The accumulation of HRP reaction products in the cerebral cortex and thalamus regions of WAG/Rij rats with CD increased and was higher than that of the control and WAG/Rij animals (p<0.01). CONCLUSION: In our study, we showed that number and duration of SWDs decreased and SWD frequency increased in WAG/Rij rats with CD, suggesting a shift in seizure pattern. The association of these alterations with significant loss of cortical thickness and increased BBB permeability to HRP tracer may represent a causal relation of the EEG abnormalities with cerebral structural changes in these animals.

Analysis of heart rate variability and risk factors for SUDEP in patients with drug-resistant epilepsy.

BACKGROUND: Cardiac problems have been suggested as causes of sudden unexpected death in epilepsy (SUDEP). Our aim was to investigate possible associations of cardiac autonomic functions based on heart rate variability (HRV) parameters with risk factors of SUDEP in patients with drug-resistant epilepsy. METHODS: Forty-seven patients with drug-resistant seizures and 45 healthy control subjects were enrolled in the study. Interictal time domain parameters of HRV were evaluated with 24-hour Holter recordings. Potential SUDEP risk in patients with epilepsy was estimated using an inventory of seven validated SUDEP risk factors (The SUDEP-7 inventory). RESULTS: When compared with the healthy controls, all time domain measures (SDNN-24, SDNN-index, SDANN-index, RMSSD and pNN50) were significantly suppressed in the patient group. Scores of the SUDEP-7 inventory ranged from 1 to 9 with a median 4 out of a maximum possible risk score of 10. Maximum heart rate value in 24-hour Holter recordings and epilepsy duration were correlated with the SUDEP-7 scores (r=0.3, p=0.03). We found no significant association with HRV measures and SUDEP-7 risk factors. One patient diagnosed with Dravet syndrome died of SUDEP, which was autopsy confirmed; his SUDEP-7 inventory score was 7, HRV measures were significantly diminished, and his maximum heart rate (HR) was 208beats/min (maximum HR is between 104 and 188beats/min in normal subjects). CONCLUSION: Patients with drug-resistant epilepsy present with significantly lower HRV measures, which may increase the risk for sudden cardiac death. Increased heart rate and diminished HRV measures may constitute one of the possible mechanisms underlying SUDEP and should be diagnosed in patients with epilepsy.

Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: Our aim was to investigate the prevalence of neuronal autoantibodies (NAbs) in a large consecutive series with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to elucidate the clinical and laboratory clues for detection of NAbs in this prototype of frequent, drug-resistant epilepsy syndrome. METHODS: Consecutive patients diagnosed with MTLE fulfilling the MRI criteria for HS were enrolled. The sera of patients and various control groups (80 subjects) were tested for eight NAbs after ethical approval and signed consents. Brain tissues obtained from surgical specimens were also investigated by immunohistochemical analysis for the presence of inflammatory infiltrates. The features of seropositive versus seronegative groups were compared and binary logistic regression analysis was performed to explore the differentiating variables. RESULTS: We found antibodies against antigens, contactin-associated protein-like 2 in 11 patients, uncharacterised voltage-gated potassium channel (VGKC)-complex antigens in four patients, glycine receptor (GLY-R) in 5 patients, N-methyl-d-aspartate receptor in 4 patients and γ-aminobutyric acid receptor A in 1 patient of 111 patients with MTLE-HS and none of the control subjects. The history of status epilepticus, diagnosis of psychosis and positron emission tomography or single-photon emission CT findings in temporal plus extratemporal regions were found significantly more frequently in the seropositive group. Binary logistic regression analysis disclosed that status epilepticus, psychosis and cognitive dysfunction were statistically significant variables to differentiate between the VGKC-complex subgroup versus seronegative group. CONCLUSIONS: This first systematic screening study of various NAbs showed 22.5% seropositivity belonging mostly to VGKC-complex antibodies in a large consecutive series of patients with MTLE-HS. Our results indicated a VGKC-complex autoimmunity-related subgroup in the syndrome of MTLE-HS.

Reappraisal of epileptic pain as a rare symptom of seizures.

PURPOSE: To draw attention to epileptic pain which is a rare seizure symptom mostly causing wrong diagnosis and delayed treatment. We present nine patients in whom pain was a prominent initial or early ictal symptom. METHODS: We reviewed the records of 4736 patients, and found nine patients who had pain as an aura or an early prominent symptom of their seizures. Seizure semiology, EEG, and cranial imaging features were evaluated retrospectively. RESULTS: Age at seizure onset ranged from 6 months to 50 years, and the mean age during the study was 37.7±11.9 years. Pain was predominantly peripherally localized in four patients, whereas cephalic pain was detected in three patients, and abdominal pain was detected in two patients. Electroencephalography (EEG) revealed epileptic abnormalities on the temporoparietal and frontotemporal regions in three patients each. Photosensitive generalized epileptic discharges were detected in one and diffuse background slowing in the remaining two other patients. Electroencephalography abnormalities were lateralized to the contralateral site of the pain in four patients with strictly localized pain. Three patients revealed no abnormality on the cranial MR imaging, whereas others showed different types of abnormality such as heterotopias (n:1), mesial temporal lobe atrophy (n:1), white and gray matter sequela lesions (n:1), diffuse white matter lesion (n:1), chronic encephalomalacia and gliosis (n:1), and perivascular space dilatation (n:1). CONCLUSION: Epileptic pain is a neglected, but important, semiologic symptom with localization and lateralization value in the patients with somatosensorial seizures of parietal as well as temporal lobe origin. It occurs mainly as peripherally localized, cephalic, or abdominal pain and is usually associated with a symptomatic etiology. Awareness of epileptic pain is important to avoid misdiagnosis and delayed treatment.

Attitudes towards epilepsy among a sample of Turkish patients with epilepsy.

OBJECTIVE: The attitude of patients with epilepsy towards their disease is an important factor in disease management and quality of life. The aim of this study was to define the attitudes of patients with epilepsy towards their disease and the factors that affect their attitudes. PATIENTS AND METHOD: This descriptive study was performed on patients admitted to an epilepsy outpatient clinic of a university hospital between May and September 2015. The sample consisted of 70 patients over 18years of age with a diagnosis of epilepsy and no health problem other than epilepsy. Patients with no seizure in the last two years were excluded. The Epilepsy Attitude Scale was used to evaluate attitudes of the patients towards epilepsy; the Epilepsy Knowledge Scale, Rotter's Locus of Control Scale, Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy-10 (QOLIE-10) were used to investigate the attitude-related factors. RESULTS: Among the 70 participants, 43 were female, and the mean age was 31.4years. The educational level of the patients was lower (primary school) in 38.6% of the sample, and 18.6% were unemployed. Time since diagnosis was 15.1years, 75.7% of the participants had generalized type of seizures, and more than half had seizures more frequently than once a month. The mean score of the attitude scale was 59.7±6.62 (range: 14-70). The attitudes of the patients towards epilepsy were found to be related to their educational status, living alone, and the attitudes of their families. The attitude scores were also related to the level of knowledge on epilepsy, stigma, and depression. Furthermore, the attitude was found to be correlated with quality of life. CONCLUSION: Patients with epilepsy had moderate-to-good attitude towards their disease. It was observed that the attitude was related to the knowledge, stigma, and depression rather than to demographic factors and the seizures, and furthermore, the attitude was found to be correlated with quality of life.

Status epilepticus in patients with juvenile myoclonic epilepsy: Frequency, precipitating factors and outcome.

Status epilepticus (SE) is rarely described in patients with juvenile myoclonic epilepsy (JME), and little is known about its frequency, subtypes, and predictors and the prognosis of these patients. In this retrospective study, we aimed to analyze the incidence of SE in patients with JME and emphasize the risk factors and long-term outcome of SE in an epilepsy outpatient-based cohort. We included patients with JME with a history of predominant myoclonic seizures and at least one diagnostic EEG with normal background activity and bursts of typical ≥3-Hz generalized spike-polyspike and waves. We investigated the electroclinical features of patients with JME who had experienced SE and compared them with patients with JME without SE. Of the 133 patients with JME, only 5 patients were diagnosed with SE (3.8%) according to new criteria. The most common SE subtype was myoclonic SE (MSE, 4 patients), followed by generalized clonic-tonic-clonic SE (1 patient) and nonconvulsive SE (1 patient). One patient had both MSE and generalized clonic-tonic-clonic SE. In three out of five patients, recurrent episodes of SE were observed. Same seizure precipitants including sleep deprivation, inappropriate antiepileptic drug treatment, and noncompliance were identified in patients with JME with and without SE, not reaching a significant difference between the groups. Myoclonia limited to specific body parts (one arm, face, or head) were significantly more common in patients with JME with SE (p: 0.002). We did not find any significant correlation with drug-resistant course and SE. Status epilepticus is rarely observed in patients with JME, and MSE appears to be the most common subtype. Local myoclonia might predict SE in a subgroup of patients with JME. We may suggest that some patients with JME have a liability to SE, in addition to usual seizure precipitating factors of JME. It seems that SE per se does not affect the outcome of JME and the patients with SE did not have drug-resistant course in the final analysis.