Showing papers in "Seizure-european Journal of Epilepsy in 2015"

Wavelet-based EEG processing for computer-aided seizure detection and epilepsy diagnosis.

Abstract: Electroencephalography (EEG) is an important tool for studying the human brain activity and epileptic processes in particular. EEG signals provide important information about epileptogenic networks that must be analyzed and understood before the initiation of therapeutic procedures. Very small variations in EEG signals depict a definite type of brain abnormality. The challenge is to design and develop signal processing algorithms which extract this subtle information and use it for diagnosis, monitoring and treatment of patients with epilepsy. This paper presents a review of wavelet techniques for computer-aided seizure detection and epilepsy diagnosis with an emphasis on research reported during the past decade. A multiparadigm approach based on the integration of wavelets, nonlinear dynamics and chaos theory, and neural networks advanced by Adeli and associates is the most effective method for automated EEG-based diagnosis of epilepsy.

Prevalence of epilepsy among people with intellectual disabilities: A systematic review

Abstract: Purpose Epilepsy is more common in people with intellectual disabilities than in the general population. However, reported prevalence rates vary widely between studies. This systematic review aimed to provide a summary of prevalence studies and estimates of prevalence based on meta-analyses. Method Studies were identified via electronic searches using Medline, Cinahl and PsycINFO and cross-citations. Information extracted from studies was tabulated. Prevalence rate estimates were pooled using random effects meta-analyses and subgroup analyses were conducted. Results A total of 48 studies were included in the tabulation and 46 studies were included in meta-analyses. In general samples of people with intellectual disabilities, the pooled estimate from 38 studies was 22.2% (95% CI 19.6–25.1). Prevalence increased with increasing level of intellectual disability. For samples of people with Down syndrome, the pooled estimate from data in 13 studies was 12.4% (95% CI 9.1–16.7), decreasing to 10.3% (95% CI 8.4–12.6) following removal of two studies focusing on older people. Prevalence increased with age in people with Down syndrome and was particularly prevalent in those with Alzheimer's/dementia. Conclusion Epilepsy is highly prevalent in people with intellectual disabilities. Services must be equipped with the skills and information needed to manage this condition.

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation

Abstract: Purpose This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Methods Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Results Sixty-six seizures ( n =16 patients) were available from the EMU for analysis. In 37 seizures ( n =14 patients) a ≥20% heart rate increase was found and 11 ( n =5 patients) were associated with ictal tachycardia (iTC, 55% or 35bpm heart rate increase, minimum of 100bpm). Multiple CBSDA settings achieved a sensitivity of ≥80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ±2min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months ( p n =8/27). Safety profiles were comparable to prior VNS trials. Conclusions The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.

Interactions between antiepileptic drugs and hormones

Abstract: Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation.

Ketamine for the treatment of refractory status epilepticus

Abstract: Status epilepticus (SE) is an acute and severe illness of the central nervous system, and prolonged SE can lead to brain damage and even death. Ketamine is a noncompetitive antagonist of glutamatergic N-methyl-d-aspartate (NMDA) receptors. During prolonged seizures, the numbers and activities of GABA receptors gradually decrease; thus, the commonly used first-line and second-line antiepileptic drugs gradually fail. Simultaneously, the numbers and activities of glutamatergic NMDA receptors increase, often causing refractory status epilepticus (RSE) and thus providing the possibility of the use of ketamine to treat RSE. To improve the prognosis of SE, we present a narrative review of ketamine for the treatment of RSE in the extant literature. We draw the conclusion that ketamine appears to be effective and relatively safe for the control of multidrug-resistant RSE in children and adults.

Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure

Abstract: Post-traumatic epilepsy continues to be a major concern for those experiencing traumatic brain injury. Post-traumatic epilepsy accounts for 10-20% of epilepsy cases in the general population. While seizure prophylaxis can prevent early onset seizures, no available treatments effectively prevent late-onset seizure. Little is known about the progression of neural injury over time and how this injury progression contributes to late onset seizure development. In this comprehensive review, we discuss the epidemiology and risk factors for post-traumatic epilepsy and the current pharmacologic agents used for treatment. We highlight limitations with the current approach and offer suggestions for remedying the knowledge gap. Critical to this pursuit is the design of pre-clinical models to investigate important mechanistic factors responsible for post-traumatic epilepsy development. We discuss what the current models have provided in terms of understanding acute injury and what is needed to advance understanding regarding late onset seizure. New model designs will be used to investigate novel pathways linking acute injury to chronic changes within the brain. Important components of this transition are likely mediated by toll-like receptors, neuroinflammation, and tauopathy. In the final section, we highlight current experimental therapies that may prove promising in preventing and treating post-traumatic epilepsy. By increasing understanding about post-traumatic epilepsy and injury expansion over time, it will be possible to design better treatments with specific molecular targets to prevent late-onset seizure occurrence following traumatic brain injury.

Interactions between hormones and epilepsy.

Abstract: There is a complex, bidirectional interdependence between sex steroid hormones and epilepsy; hormones affect seizures, while seizures affect hormones thereby disturbing reproductive endocrine function. Both female and male sex steroid hormones influence brain excitability. For the female sex steroid hormones, progesterone and its metabolites are anticonvulsant, while estrogens are mainly proconvulsant. The monthly fluctuations in hormone levels of estrogen and progesterone are the basis for catamenial epilepsy described elsewhere in this issue. Androgens are mainly anticonvulsant, but the effects are more varied, probably because of its metabolism to, among others, estradiol. The mechanisms for the effects of sex steroid hormones on brain excitability are related to both classical, intracellularly mediated effects, and non-classical membrane effects due to binding to membrane receptors. The latter are considered the most important in relation to epilepsy. The different sex steroids can also be further metabolized within the brain to different neurosteroids, which are even more potent with regard to their effect on excitability. Estrogens potentiate glutamate responses, primarily by potentiating NMDA receptor activity, but also by affecting GABA-ergic mechanisms and altering brain morphology by increasing dendritic spine density. Progesterone and its main metabolite 5α-pregnan-3α-ol-20-one (3α-5α-THP) act mainly to enhance postsynaptic GABA-ergic activity, while androgens enhance GABA-activated currents. Seizures and epileptic discharges also affect sex steroid hormones. There are close anatomical connections between the temporolimbic system and the hypothalamus controlling the endocrine system. Several studies have shown that epileptic activity, especially mediated through the amygdala, alters reproductive function, including reduced ovarian cyclicity in females and altered sex steroid hormone levels in both genders. Furthermore, there is an asymmetric activation of the hypothalamus with unilateral amygdala seizures. This may, again, be the basis for the occurrence of different reproductive endocrine disorders described for patients with left-sided or right-sided temporal lobe epilepsy.

Catamenial epilepsy: Update on prevalence, pathophysiology and treatment from the findings of the NIH Progesterone Treatment Trial

Abstract: Purpose To extend our knowledge and practical application of the concept of catamenial epilepsy. Methods The review focuses on the impact of the NIH Progesterone Trial on our understanding of the pathophysiology and treatment of catamenial epilepsy. Results Catamenial epilepsy refers to the cyclic exacerbation of seizures in relation to the menstrual cycle. An interaction between seizures and the menstrual cycle is suggested by variations in seizure frequency according to the day, phase and ovulatory status of the menstrual cycle. There are three commonly recognized patterns: perimenstrual (C1: Day −3 to +3), peri-ovulatory (C2: Day 10 to 3) and entire luteal phase in anovulatory cycles (C3: Day 10 to 3). Pathophysiological determinants include 1) the neuroactive properties of reproductive steroids, 2) the variation of neuroactive steroid levels across the menstrual cycle and 3) the differential susceptibility of epileptic substrates to neuroactive steroid effects. Perimenstrual seizure exacerbation may result from the premenstrual withdrawal of progesterone which is accompanied by withdrawal of allopregnanolone, a potent positive allosteric modulator of the GABA A receptor, and changes in the subunit composition of the GABA A receptor to the α4 subtype which is insensitive to benzodiazepine and GABA. Bioidentical progesterone supplement is no better than placebo in the treatment of women with focal onset epilepsy overall but shows superior efficacy in women whose seizures show robust perimenstrual exacerbation. Conclusion There is sound evidence for the existence of catamenial epilepsy and class 3 evidence for adjunctive progesterone treatment of the perimenstrually exacerbated subtype.

Amplitude-integrated EEG for detection of neonatal seizures: a systematic review.

Abstract: Purpose Amplitude-integrated electroencephalogram (aEEG) is being used increasingly for monitoring seizures in neonatal units. Its accuracy, compared with "the gold-standard" conventional elecroencephalogram (cEEG) is still not well established. We aimed to conduct a systematic review to evaluate the diagnostic accuracy of aEEG when compared with cEEG, for detection of neonatal seizures. Method A systematic review was conducted using the Cochrane methodology. EMBASE, CINAHL and PubMed databases were searched in September 2014. Studies comparing simultaneous recordings of cEEG and aEEG for detection of seizures in neonatal population were included. QUADAS 2 tool was used to examine "risk of bias" and "applicability". Results Ten studies (patient sample 433) were included. Risk of bias was high in five studies, unclear in one and low in four. For the detection of individual seizures, when "aEEG with raw trace" was used, median sensitivity was 76% (range: 71–85), and specificity 85% (range: 39–96). When "aEEG without raw trace" was used, median sensitivity was 39% (range: 25–80) and specificity 95% (range: 50–100). Detailed meta-analysis could not be done because of significant clinical/methodological heterogeneity. Seizure detection was better when interpreted by experienced clinicians. Seizures with low amplitude/brief duration and those occurring away from aEEG leads were less likely to be detected. Conclusion Studies included in the systematic review showed aEEG to have relatively low and variable sensitivity and specificity. Based on the available evidence, aEEG cannot be recommended as the mainstay for diagnosis and management of neonatal seizures. There is an urgent need of well-designed studies to address this issue definitively.

CSF findings in patients with anti-N-methyl-d-aspartate receptor-encephalitis

Abstract: Purpose Anti-NMDAR-encephalitis is a recently described form of autoimmune encephalitis. Here, we characterize CSF changes in Chinese patients with anti-NMDAR encephalitis, and explore the relationship between CSF findings and disease outcome. Methods The presence of NMDAR antibodies in serum or CSF samples was evaluated in patients diagnosed with encephalitis between October 1, 2010 and August 1, 2014 at the West China Hospital. All patients fulfilling our diagnostic criteria were included and CSF findings were analyzed. Patient outcome was assessed after 4, 8, 12, 16, 20, and 24 months using the modified Rankin scale (mRS). Results Out of 3000 people with encephalitis screened, 43 patients were anti-NMDAR antibody positive in CSF or serum and included in this study. 62.8% of the patients identified with positive CSFs had positive serum anti-NMDAR samples, while 100% patients with positive serum had positive CSF samples. In the CSF white cell counts were elevated in 58.1% of cases; protein was increased in 18.6%; QAlb>Qlim(Alb) of the blood–CSF barrier was found in 29.3%; intrathecal immunoglobulin synthesis was detected in 17.1%, and 39.5% patients exhibited increased CSF pressures. A longer follow-up period was associated with better outcomes. There was no relationship between changes in CSF findings and outcome. Conclusion The sensitivity of NMDA receptor antibody testing is higher in CSF compared to serum. Other CSF abnormalities are present in some patients with Anti-NMDAR-encephalitis, however these changes do not appear to affect prognosis.

Detection of epileptic seizures with a modified heart rate variability algorithm based on Lorenz plot

Abstract: Purpose In order to assess whether focal epileptic seizures can be detected and distinguished from exercise we evaluated four different heart rate variability (HRV) methods with short term moving window analysis of 30, 50 or 100 R-R intervals or seconds per analyzed window. Methods The four methods consisted of: (1) reciprocal high frequency power based on Fast Fourier Transformation, (2) Cardiac Sympathetic Index (CSI), (3) Modified CSI both based on Lorenz plot, and (4) heart rate differential method. Seventeen patients (12 males, 5 females; age 20–55) had 47 seizures (including three secondary generalized tonic–clonic (sGTC)), which were analyzed during their long term video-EEG monitoring of 1–5 days duration. Positive seizure detection was regarded, when the HRV-value during seizures (1min before to 3min after seizure-onset) exceeded 105% of the highest value during exercise and non-seizure sample-periods of the same patient. Results Modified CSI 100 was the most accurate method: it detected all seizures for 13 of the 17 patients within 6s before till 50s after seizure onset time, even though exercise maximum HR of each patient exceeded that of the seizures. The three sGTC seizures were all detected more than half a minute before the tonic–clonic phase. Conclusion The results indicate a detectable, sudden and inordinate shift toward sympathetic overdrive in the sympathovagal balance of the autonomic nervous system around seizure-onset time, for most patients. The Modified CSI is a promising parameter for a portable ECG-based epilepsy alarm, detecting both focal and sGTC seizures.

IL-1β, IL-6 and IL1Ra levels in temporal lobe epilepsy

Abstract: Purpose There is now extensive evidence to support the involvement of inflammation in the course of epileptic seizures. Seizure-induced changes in serum IL-1β, IL-6 and IL-1Ra levels are reported in several studies. Serum cytokine levels may also be disturbed in inter-ictal period due to seizure activity. Methods Twenty-one patients (12 women; mean age 35±12.3) with temporal lobe epilepsy (TLE), 17 patients (8 women; mean age 31.8±10.4) with extra-temporal lobe epilepsy (XLE) and 20 normal controls (10 women; mean age 35.6±8.8) were included in the study. Serum levels of IL-1β, IL-6 and IL-1Ra of the TLE, XLE groups in inter-ictal period and of the normal control group were compared. Results All three cytokine levels are found to be significantly elevated in epilepsy patients when compared to controls ( p p Conclusion The major findings in our study were increased levels of IL-1β, IL-6 and IL-1Ra in epileptic patients and high levels of IL-1β in TLE group. Our results support the existence of a chronic inflammatory state in epileptic patients.

Major congenital malformations in children of women with epilepsy

Abstract: It has been long known that the risk of major congenital malformations is increased among children of mothers with epilepsy. This is mainly due to the teratogenic effects of antiepileptic drugs although other factors, such as genetically determined individual susceptibility, are likely to contribute. Recent large scale prospective epilepsy and pregnancy registries have indicated that the rate of major congenital malformations may be at most two-fold higher than expected with exposure in utero to the presently most frequently used antiepileptic drugs such as carbamazepine or lamotrigine. Higher rates are consistently reported with exposure to valproate. The risk of teratogenic effects appears to be dose dependent and the lowest effective dose should thus be established before pregnancy regardless of which antiepileptic drug the woman is taking. Major changes such as switches between drugs should be avoided when pregnancy is established.

Epilepsy and physical exercise

Abstract: A B S T R A C T Epilepsy is one of the commonest neurologic diseases and has always been associated with stigma. In the interest of safety, the activities of persons with epilepsy (PWE) are often restricted. In keeping with this, physical exercise has often been discouraged. The precise nature of a person’s seizures (or whether seizures were provoked or unprovoked) may not have been considered. Although there has been a change in attitude over the last few decades, the exact role of exercise in inducing seizures or aggravating epilepsy still remains a matter of discussion among experts in the field. Based mainly on retrospective, but also on prospective, population and animal-based research, the hypothesis that physical exercise is prejudicial has been slowly replaced by the realization that physical exercise might actually be beneficial for PWE. The benefits are related to improvement of physical and mental health parameters and social integration and reduction in markers of stress, epileptiform activity and the number of seizures. Nowadays, the general consensus is that there should be no restrictions to the practice of physical exercise in people with controlled epilepsy, except for scuba diving, skydiving and other sports at heights. Whilst broader restrictions apply for patients with uncontrolled epilepsy, individual risk assessments taking into account the seizure types, frequency, patterns or triggers may allow PWE to enjoy a wide range of physical activities.

Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies.

Abstract: Purpose Temporal lobe epilepsy with antibodies (abs) against the glutamic acid decarboxylase 65 isoform (GAD-TLE) is known as an immune-mediated neurological syndrome. Here we evaluate the therapy response to various immunotherapies and epilepsy surgery in this syndrome. Method All patients with GAD-TLE and follow-up data and stored serum and CSF samples, identified and treated at the Bonn centre from 2002 to 2010, were studied retrospectively. Seizure freedom for ≥1 year and reduction of ≥50%, i.e. therapy response, were assessed. GAD-ab titres and neuropsychological performances were documented prior and after individual interventions. Results Thirteen patients with GAD-TLE were identified with the following seizure responses: corticosteroids (5 responders out of 11 treated patients); i.v. immunoglobulins (1/5), apheresis therapy (1/8); and natalizumab (1/1), selective amygdala-hippocampectomy (2/3). None of the patients achieved sustained seizure freedom apart from one patient. This patient was on antiepileptic drug treatment after discontinuation of immunotherapy. Conclusion The seizure response to immunotherapies in patients with GAD-TLE was poor. Corticosteroids were the most effective regarding seizure response. Especially the poor effects of apheresis therapies support the idea that GAD-abs are not directly pathogenic. None of three patients was seizure-free after temporal lobe surgery suggesting that GAD-TLE patients respond worse than others to this type of intervention. Our results reflect the chronic course of the disease with low likelihood for patients with GAD-TLE to attain long-term seizure freedom.

The impact of seizures on pregnancy and delivery

Abstract: Purpose and methods The treatment of women with epilepsy during pregnancy is known to increase the risk of teratogenic effects. Whether seizures during pregnancy have a deleterious effect on the developing child is difficult to determine, but recent animal studies, case studies, cohort studies and population studies have provided useful insights. Results and conclusion Seizures before pregnancy are a predictor for seizures during pregnancy, and catamenial epilepsy may also predict the course of seizures during pregnancy. A first epileptic seizure may also have implications for the pregnancy, depending on the seizure aetiology. Seizures affecting maternal awareness and responsiveness may have cardiac effects on the foetus and may impact on the weight of the newborn. Status epilepticus in pregnancy is rare, but isolated cases of perinatal death and malformations after status epilepticus have been reported in women on antiepileptic drugs. Seizures during delivery occur in about 2% of pregnancies of women with epilepsy, and case studies indicate that the foetal heart may be affected. However, a diagnosis of epilepsy is not an indication per se for caesarean delivery. A well-planned pregnancy can reduce the likelihood of seizures occurring.

The adverse event profile of levetiracetam: A meta-analysis on children and adults

Abstract: Purpose To analyze the adverse events (AEs) significantly associated with levetiracetam (LEV) therapy through a meta-analysis of all available double-blind, randomized placebo-controlled trials (RCTs), performed in any age, gender, ethnic background and disease. General tolerability and study withdrawals due to AEs associated with LEV treatment were also investigated. In addition, a dose–effect responses relationship for all variables was assessed. Methods RCTs were identified searching Medline (PubMed), Embase and Cochrane CENTRAL for the words "Levetiracetam" and "randomized controlled trial", with different search strategies, setting the limits "humans" and "English". Very common and common AEs according to the summary of product characteristics were investigated. RevMan version 5.2 was used for the statistical analyses. Risk difference with 95% confidence intervals was used to investigate the association of any AEs and withdrawal with LEV. Results Twenty-six studies with 2832 patients were included in the RCTs analysis. Nasopharyngitis, somnolence, dizziness, nervousness/irritability and asthenia/fatigue were statistically significant associated with LEV. In addition, LEV was significantly associated with an increased risk of AEs-related withdrawals. No dose–response relationship was found for any of the assessed variables. Conclusions This first large meta-analysis suggests that participants were more likely to discontinue LEV than placebo. The AE profile confirmed that LEV is associated with few unfavorable sedative, vestibulocerebellar and behavioral effects, such as nervousness and irritability. However, there does not seem to be a clear dose–response relationship.

The perceived burden of epilepsy: Impact on the quality of life of children and adolescents and their families.

Abstract: Purpose The assessment of the quality of life (QoL) is relevant for a comprehensive treatment of patients with epilepsy. In children and adolescents, an impact of epilepsy on the QoL of the entire family is expected. Methods We asked 293 parents of children and adolescents with epilepsy, included in an observational study on treatment satisfaction, to evaluate the impact of the disease on several aspects of the QoL of the whole family using a specifically organized questionnaire (IEQoL). Results The degree of parents' concerns about epilepsy and the severity of the disease correlated with a deterioration of QoL in both the children and the family. This involved all aspects of QoL (conflicts within the family, job, leisure activities, peer relationship, economy) although to a different degree. Parents frequently admitted increased apprehensiveness, even when not justified by the low severity of the disease. There was general agreement between parents and their adolescent children, although in a few cases adolescents overrated their school and daily performance in respect to the parents, suggesting a tendency to overlook their problems. Conclusion Epilepsy impairs all aspects of QoL, although at different degree, both in children/adolescents and in their families. Parental apprehensiveness appears to have a role on this, and it may not reflect the severity of the disease.

Cognition in the early stages of adult epilepsy

Abstract: Purpose The impact of duration of epilepsy on cognition has been discussed for a long time. More recently, it has been recognized that cognitive deficits are often already present at the onset of epilepsy or even before. From an etiological point of view it is now understood that it is not really the question what comes first, epilepsy or cognitive comorbidity. Instead the evidence suggests that both problems rather originate from a common underlying pathology. Methods We selected studies addressing cognition in adult new-onset or newly diagnosed epilepsies before treatment initiation. Potential factors are outlined that affect cognition prior to, around or after epilepsy onset. Results Most studies investigated newly diagnosed patients, but many included individuals who already had a long history of seizures at the time of diagnosis. Fewer studies focused on new-onset epilepsies. Overall, cognitive problems in the early stages of adult onset epilepsy were found to be common. The occurrence of seizures may initially cause greater concern and lead to an underreporting of cognitive problems prior to or around the time of diagnosis. Conclusion The high prevalence of objective cognitive impairments present at epilepsy onset calls for early neuropsychological assessments soon after the diagnosis of epilepsy, and at best before medical treatment is initiated. Without such baseline assessments subsequent neuropsychological testing during follow-up is difficult to interpret in regard to the effects of treatment success or the course of underlying disease processes. Beyond that, the baseline assessment may also guide treatment choices and serve as an early indicator of the need for support or rehabilitation. In this way neuropsychological monitoring can improve individual medical care, and increase tolerability, adherence, and treatment retention from the point of diagnosis.

Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations

Abstract: Antiepileptic drugs (AEDs) and hormonal contraceptives may affect each other's metabolism and clinical efficacy. Loss of seizure control and unplanned pregnancy may occur when these compounds are used concomitantly. Although a large number of available preparations yield a plethora of possible drug combinations, most of these drug interactions are predictable and, thus, avoidable. Unfortunately, there is a substantial lack of data regarding the newer AEDs. Detailed understanding of these issues is necessary for those who prescribe AEDs and/or hormonal contraception to women with epilepsy, as well as for those who provide comprehensive care, education and counseling to them, in order to reduce the unacceptably high number of unplanned pregnancies among women with epilepsy.

Does intellectual disability increase sudden unexpected death in epilepsy (SUDEP) risk

Abstract: Purpose An estimated 1.4 million people in the United Kingdom (UK) have intellectual disability (ID) with 210,000 having severe or profound ID. Of these, approximately 125,000 have epilepsy, representing one quarter of all patients with epilepsy in the UK. For those with full scale intellectual quotients (FSIQs) of less than 50, half have epilepsy, with half of these having treatment resistant epilepsy. One of the two major causes of mortality within this population is sudden unexpected death in epilepsy (SUDEP). Methods We performed a literature review exploring the extent to which ID was considered as a risk factor for SUDEP. We also considered whether there was any relationship between the types of health care system in which the studies were conducted and whether ID was considered in studies of SUDEP. Results We identified 49 studies which had explored risk factors for SUDEP, of which, approximately 50% ( n =23) considered ID in the planning stages. Of these studies 60% ( n =14) found ID was a risk factor for SUDEP. 60% of all the studies were conducted in countries where the health care system was publicly funded. Conclusions Overall we found ID definitions and specified standardized mortality rates and impact of institutionalization to be quite poorly presented.

Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms.

Abstract: This narrative review is intended to introduce clinicians treating epilepsy and researchers familiar with mammalian models of epilepsy to experimentally tractable, non-mammalian research models used in epilepsy research, ranging from unicellular eukaryotes to more complex multicellular organisms. The review focuses on four model organisms: the social amoeba Dictyostelium discoideum, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. We consider recent discoveries made with each model organism and discuss the importance of these advances for the understanding and treatment of epilepsy in humans. The relative ease with which mutations in genes of interest can be produced and studied quickly and cheaply in these organisms, together with their anatomical and physiological simplicity in comparison to mammalian species, are major advantages when researchers are trying to unravel complex disease mechanisms. The short generation times of most of these model organisms also mean that they lend themselves particularly conveniently to the investigation of drug effects or epileptogenic processes across the lifecourse.

Long-term seizure outcome for international consensus classification of hippocampal sclerosis: A survival analysis

Abstract: Purpose Surgery is regarded as a common treatment option for patients with mesial temporal lobe epilepsy (MTLE) as a result of hippocampal sclerosis (HS) However, approximately one-third of patients with intractable epilepsy did not become seizure-free after tailored resection strategies It would be compelling to identify predictive factors of postoperative seizure outcomes Our aim was to assess the correlation between HS classification and long-term postoperative seizure outcome in patients with MTLE due to HS Methods To investigate HS classification, semi-quantitative analysis and immunohistochemical staining of neuronal nuclei (NeuN) were performed on 100 postoperative hippocampal specimens All patients had a 1–7 year postoperative follow-up The postoperative seizure outcome was evaluated using International League Against Epilepsy (ILAE) outcome classification Results Three types of HS were recognized The highest incidence of initial precipitating injury (IPI) was noted in the HS ILAE type 1 group (531%) The most favorable long-term seizure outcome was also noted in the HS ILAE type 1 group The shortest epilepsy duration was recorded in the HS ILAE type 2 group (mean epilepsy duration=664±583 years) The completely seizure free rate of patients in all groups declined with an increase in time Conclusions Our study for the first time demonstrated a significant correlation between HS ILAE types and long-term postoperative seizure outcome in patients with MTLE due to HS Therefore, HS ILAE types have predictive value in long-term seizure outcome following epilepsy surgery

Epilepsy and recommendations for breastfeeding

Abstract: Purpose The objective of this paper is to provide a synopsis of benefits and potential harmful effects of exposure to antiepileptic drugs (AEDs) via breastmilk, and present recommendations for breastfeeding in women with epilepsy. Methods The article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, the LactMed database, and the authors' clinical experience. Results Breastfeeding is associated with benefits for the infant, including nutrition, protection against infectious and immunological disease, and promotion of development and psychological attachment. Exposure to AEDs via breastmilk could potentially produce side effects or negatively affect development. Most studies on AED transfer through breastmilk report infant serum levels well below the limit of an expected pharmacological effect. Some drugs have the potential to reach significant serum levels in breastfed infants, such as barbiturates, benzodiazepines, lamotrigine, and ethosuximide. Thus, breastfed infants should be monitored for side effects. Still, adverse symptoms are rarely reported in breastfed infants of mothers taking AEDs, and prospective studies have failed to demonstrate any negative developmental effects in children that have been exposed to AEDs via breastmilk. The nursing infant's degree of drug exposure can be minimized by breastfeeding when drug concentrations in the milk are low, reducing maternal AED dosage to prepregnancy levels, and administering mixed nutrition. Conclusion Most AEDs are considered safe or moderately safe during breastfeeding. Mothers with epilepsy should be encouraged to breastfeed, provided careful monitoring of the infant.

Seizure reporting technologies for epilepsy treatment: A review of clinical information needs and supporting technologies.

Abstract: This review surveys current seizure detection and classification technologies as they relate to aiding clinical decision-making during epilepsy treatment. Interviews and data collected from neurologists and a literature review highlighted a strong need for better distinguishing between patients exhibiting generalized and partial seizure types as well as achieving more accurate seizure counts. This information is critical for enabling neurologists to select the correct class of antiepileptic drugs (AED) for their patients and evaluating AED efficiency during long-term treatment. In our questionnaire, 100% of neurologists reported they would like to have video from patients prior to selecting an AED during an initial consultation. Presently, only 30% have access to video. In our technology review we identified that only a subset of available technologies surpassed patient self-reporting performance due to high false positive rates. Inertial seizure detection devices coupled with video capture for recording seizures at night could stand to address collecting seizure counts that are more accurate than current patient self-reporting during day and night time use.

Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1 pathogenic variant

Abstract: Purpose Ion channels are expressed both in the heart and in the brain, being advocated as responsible for sudden unexpected death in epilepsy but few pathogenic mutations have been identified. We aim to identify a novel gen associated with channelopathies and epilepsy in a family. Methods We assessed a family showing epilepsy concomitant with LQTS. Index case showed prolonged QT interval. His father suffers of LQT and epilepsy. We performed a direct sequencing analysis of KCNQ1 , KCNH2 , KCNE1 , KCNE2 and SCN5A genes. Results We identified a non-synonymous heterozygous missense pathogenic mutation (p.L273F) in exon 6 of the KCNQ1 gene. All clinically affected relatives carried the same mutation. Conclusion We report, for a first time, a KCNQ1 mutation in a family suffering of both phenotypes, suggesting that KCNQ1 genetic variations may confer susceptibility for recurrent seizure activity increasing the risk or lead to sudden death.

How important is the seizure onset zone for seizure dynamics

Abstract: Purpose Research into epileptic networks has recently allowed deeper insights into the epileptic process. Here we investigated the importance of individual network nodes for seizure dynamics. Methods We analysed intracranial electroencephalographic recordings of 86 focal seizures with different anatomical onset locations. With time-resolved correlation analyses, we derived a sequence of weighted epileptic networks spanning the pre-ictal, ictal, and post-ictal period, and each recording site represents a network node. We assessed node importance with commonly used centrality indices that take into account different network properties. Results A high variability of temporal evolution of node importance was observed, both intra- and interindividually. Nevertheless, nodes near and far off the seizure onset zone (SOZ) were rated as most important for seizure dynamics more often (65% of cases) than nodes from within the SOZ (35% of cases). Conclusion Our findings underline the high relevance of brain outside of the SOZ but within the large-scale epileptic network for seizure dynamics. Knowledge about these network constituents may elucidate targets for individualised therapeutic interventions that aim at preventing seizure generation and spread.

Polymorphism of the Multidrug Resistance 1 Gene MDR1/ABCB1 C3435T and Response to Antiepileptic Drug Treatment in Temporal Lobe Epilepsy

Abstract: Purpose A synonymous C to T variant at position 3435 (c.3435C>T) is one common polymorphism of the multidrug resistant 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein. It has been suggested that this polymorphism, and more specifically the 3435CC genotype, may be associated with the response to antiepileptic drug treatment. Here we wished to examine the role of such a candidate variant in a cohort of 175 patients (98 women and 76 men; mean±SD age: 47.90±17.64) with temporal lobe epilepsy (TLE). Methods Patients were classified according to whether they had drug-responsive ( n =134) or drug-resistant ( n =41) epilepsy. We also enrolled 175 healthy controls (93 women and 82 men; mean±SD age: 72.5±6.8), matched for sex and ethnicity. Results Patients and controls were genotyped for detection of the 3435C>T polymorphism, but the analysis showed no significant association between the CC genotype and the risk of drug-resistant epilepsy. Conclusion These findings rule out the MDR1 c.3435C>T polymorphism having a major role or increasing the risk of drug-resistance suggesting a revision is required to determine the contribution of this polymorphism in predicting drug response in epilepsy.

Factors associated with increased felt stigma among individuals with epilepsy.

Abstract: Purpose The aim of the study is to determine whether certain demographic, clinical, and psychosocial traits are associated with higher levels of felt stigma among persons with epilepsy (PWE) patients followed at a level 4 epilepsy center. Methods We performed a direct survey of 182 consenting patients that included the Epilepsy Stigma Scale. Results On univariate analysis, higher levels of perceived stigma were associated with age, marital status, race, driving, work status, seizure etiology, Quality of Life in Epilepsy-10 (QOLIE-10) scores, and health literacy. Among coping reactions, the use of denial, behavioral disengagement and venting were also associated with higher degrees of felt stigma. Using multiple linear regression, being single, poorer QOLIE-10 scores, difficulties understanding written information, and the use of behavioral disengagement were independently associated with poorer scores on the Epilepsy Stigma Scale. Conclusion Our study paints a compelling profile of a PWE who has greater perceived stigma. Programs that increase the level of social support, improve health literacy, and enhance quality of life may also help decrease the amount of felt stigma among PWE.

Effect of health education on trainee teachers' knowledge, attitudes, and first aid management of epilepsy : An interventional study

Abstract: Purpose High rates of poor knowledge of, and negative attitudes towards people with epilepsy (PWE) are generally found among school teachers. Their first aid epilepsy management skills are poor. It remains unknown if this is different among trainee teachers and whether educational intervention might reduce these rates. We examined the effect of health education on the knowledge, attitudes, and first aid management of epilepsy on trainee teachers in Nigeria. Methods Baseline data and socio-demographic determinants were collected from 226 randomly selected trainee teachers, at the Federal College of Education, Lagos, Nigeria, with self-administered questionnaires. They received a health intervention comprising an hour and half epilepsy lecture followed by a discussion. Baseline knowledge of, and attitudes towards PWE and their first aid epilepsy management skills were compared to post-interventional follow-up data collected twelve weeks later with similar questionnaires. Results At baseline the majority (61.9%) and largest proportion (44.2%) of respondents had negative attitudes and poor knowledge of epilepsy, respectively. The knowledge of, and attitudes towards epilepsy, and the first aid management skill increased in most respondents, post-intervention. The proportion of respondents with poor knowledge and negative attitudes dropped by 15.5% ( p p p p Conclusion Epilepsy health education could increase trainee teachers' knowledge of, and attitudes towards epilepsy and facilitate correct first aid management. This emphasizes the potential benefit of incorporating an epilepsy tailored intervention programme into teachers' training curricula.