Sahin, Deniz; Karadenizli, Sabriye; Kasap, Murat; Oztas, Berrin; Kir, Hale Maral; Akpinar, Gurler; Ates, Nurbay
2018-02-06
The role of intracellular proteins in the pathogenesis of absence epilepsy were mentioned. These proteins are thought to be related to energy generation, signal transduction, inflammation processes and membrane conductance. The investigation of protein profile of the genetically epileptic rat brains was the main subject of this study. For this, a 2D-gel electrophoresis based comparative proteome analysis was performed using thalamus tissue of genetic absence epileptic WAG/Rij and age matched Wistar rats. Regulated spots displaying differences in their abundance were identified using MALDI-TOF/TOF. Among the six spots (DHRS9, BR44, HINT1, CREM, SPRE and PDIA3/ERp57) the highest mascot score was attributed to ERp57 a neuroprotective/neurodegenerative system associated protein. Western Blot analyses were performed to validate changes occurring at ERp57 in thalamus and also identify changes in fronto-parietal cortex. Reductions in the expression levels of ERp57 were detected in the thalamic and the fronto-parietal brain regions of the WAG/Rij rats in comparison to Wistar rats. Such difference might be associated with the pathogenic mechanisms dictating the absence epilepsy. Lower levels of ERp57 may be playing an important role in the development of spontaneous seizures activity seen in the absence epileptic WAG/Rij rats strain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Badiu, Carmen-Ionela
2004-11-12
Mutations in GABA-A receptor subunits have been reported in a number of idiopathic generalized epilepsies including childhood absence epilepsy. One of these mutations is located within a high-affinity benzodiazepine-binding domain, and clonazepam is clinically used as an anti-absence drug. The intrathalamic loop consisting of the GABAergic neurons of the nucleus reticularis thalami (NRT) and the thalamocortical (TC) neurons of sensory thalamic nuclei plays an essential role in spike and wave discharges. In a well-established genetic model of absence epilepsy (Genetic Absence Epilepsy rat from Strasbourg, GAERS), systemic injections of benzodiazepines have been shown to suppress spike-and-waves discharges. The aim of this study, therefore, was to determine whether the sensitivity of GABAergic synaptic currents to clonazepam in NRT and TC neurons was different in GAERS and non-epileptic control (NEC) rats. In both pre-seizure GAERS and NEC clonazepam (100 nM) had no effect on the mIPSCs recorded from TC neurons while it increased the decay time constant of the mIPSCs recorded in NRT neurons by a similar amount in GAERS (54.5+/-5%) and NEC (50.7+/-5%). Similar results have been obtained in the presence of 100 microM Cd2+, showing that the effect of clonazepam did not occur via modulation of voltage-activated Ca2+ currents. These results are relevant to understand that in GAERS, the clonazepam anti-absence actions cannot be fully explained by the enhancement of the intra-NRT inhibition and the modulation of the GABAergic synaptic currents in other brain areas, in particular the cortex, must be taken into consideration.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hramov, Alexander; Koronovskii, Alexey A.; Midzyanovskaya, I.S.
2006-12-15
In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested.
Sitnikova, Evgenia; Rutskova, Elizaveta M; Raevsky, Vladimir V
2016-10-01
WAG/Rij rats have a genetic predisposition to absence epilepsy and develop spontaneous spike-wave discharges in EEG during late ontogenesis (SWD, EEG manifestation of absence epilepsy). Changes in an environment during early postnatal ontogenesis can influence the genetically predetermined absence epilepsy. Here we examined the effect of maternal environment during weaning period on the EEG manifestation of absence epilepsy in adulthood. Experiments were performed in the offspring of WAG/Rij and Wistar rats. The newborn pups were fostered to dams of the same (in-fostering) or another strain (cross-fostering). Age-matched control WAG/Rij and Wistar rats were reared by their biological mothers. Absence seizures were uncommon in Wistar and were not aggravated in both in- and cross-fostered groups. In WAG/Rij rats, fewer SWD were found in the cross-fostered as compared to the in-fostered group. The cross-fostered WAG/Rij rats showed higher percentage of short-lasting SWD with duration <2s. The mean frequency of EEG at the beginning of SWD in the cross-fostered WAG/Rij rats was lower than in control (8.82 vs 9.25Hz), but it was higher in a period of 1.5s before and after SWD. It was concluded that a healthier maternal environment is able to alleviate genetically predetermined absence seizures in adulthood through changes in EEG rhythmic activity. Copyright © 2016 Elsevier Inc. All rights reserved.
Papp, Péter; Kovács, Zsolt; Szocsics, Péter; Juhász, Gábor; Maglóczky, Zsófia
2018-05-31
Recent data from absence epileptic patients and animal models provide evidence for significant impairments of attention, memory, and psychosocial functioning. Here, we outline aspects of the electrophysiological and structural background of these dysfunctions by investigating changes in hippocampal and cortical GABAergic inhibitory interneurons in two genetically absence epileptic rat strains: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Using simultaneously recorded field potentials from the primary somatosensory cortex (S1 cortex, seizure focus) and the hippocampal hilus, we demonstrated that typical frequencies of spike-wave discharges (SWDs; 7-8 Hz, GAERS; 7-9 Hz, WAG/Rij) and their harmonics appeared and their EEG spectral power markedly increased on recordings not only from the S1 cortex, but also from the hilus in both GAERS and WAG/Rij rats during SWDs. Moreover, we observed an increased synchronization between S1 cortex and hilus at 7-8 Hz (GAERS) and 7-9 Hz (WAG/Rij) and at their harmonics when SWDs occurred in the S1 cortex in both rat strains. In addition, using immunohistochemistry we demonstrated changes in the densities of perisomatic (parvalbumin-immunopositive, PV+) and interneuron-selective (calretinin-immunopositive, CR+) GABAergic inhibitory interneuron somata. Specifically, GAERS and WAG/Rij rats displayed lower densities of PV-immunopositivity in the hippocampal hilus compared to non-epileptic control (NEC) and normal Wistar rats. GAERS and WAG/Rij rats also show a marked reduction in the density of CR + interneurons in the same region in comparison with NEC rats. Data from the S1 cortex reveals bidirectional differences in PV + density, with GAERS displaying a significant increase, whereas WAG/Rij a reduction compared to control rat strains. Our results suggest an enhanced synchronization and functional connections between the hippocampus and S1 cortex as well
Powell, Kim L.; Zhu, Mingfu; Campbell, C. Ryan; Maia, Jessica M.; Ren, Zhong; Jones, Nigel C.; O’Brien, Terence J.; Petrovski, Slavé
2017-01-01
Objective The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbreed Wistar rat strain widely used as a model of genetic generalised epilepsy with absence seizures. As in humans, the genetic architecture that results in genetic generalized epilepsy in GAERS is poorly understood. Here we present the strain-specific variants found among the epileptic GAERS and their related Non-Epileptic Control (NEC) strain. The GAERS and NEC represent a powerful opportunity to identify neurobiological factors that are associated with the genetic generalised epilepsy phenotype. Methods We performed whole genome sequencing on adult epileptic GAERS and adult NEC rats, a strain derived from the same original Wistar colony. We also generated whole genome sequencing on four double-crossed (GAERS with NEC) F2 selected for high-seizing (n = 2) and non-seizing (n = 2) phenotypes. Results Specific to the GAERS genome, we identified 1.12 million single nucleotide variants, 296.5K short insertion-deletions, and 354 putative copy number variants that result in complete or partial loss/duplication of 41 genes. Of the GAERS-specific variants that met high quality criteria, 25 are annotated as stop codon gain/loss, 56 as putative essential splice sites, and 56 indels are predicted to result in a frameshift. Subsequent screening against the two F2 progeny sequenced for having the highest and two F2 progeny for having the lowest seizure burden identified only the selected Cacna1h GAERS-private protein-coding variant as exclusively co-segregating with the two high-seizing F2 rats. Significance This study highlights an approach for using whole genome sequencing to narrow down to a manageable candidate list of genetic variants in a complex genetic epilepsy animal model, and suggests utility of this sequencing design to investigate other spontaneously occurring animal models of human disease. PMID:28708842
NASA Astrophysics Data System (ADS)
Hramov, Alexander E.; Sitnikova, Evgenija Y.; Pavlov, Alexey N.; Grubov, Vadim V.; Koronovskii, Alexey A.; Khramova, Marina V.
2015-03-01
Sleep spindles are known to appear spontaneously in the thalamocortical neuronal network of the brain during slow-wave sleep; pathological processes in the thalamocortical network may be the reason of the absence epilepsy. The aim of the present work is to study developed changes in the time-frequency structure of sleep spindles during the progressive development of the absence epilepsy in WAG/Rij rats. EEG recordings were made at age 7 and 9 months. Automatic recognition and subsequent analysis of sleep spindles on the EEG were performed using the continuous wavelet transform. The duration of epileptic discharges and the total duration of epileptic activity were found to increase with age, while the duration of sleep spindles, conversely, decreased. In terms of the mean frequency, sleep spindles could be divided into three classes: `slow' (mean frequency 9.3Hz), `medium' (11.4Hz), and `fast' (13.5Hz). Slow and medium (transitional) spindles in five-month-old animals showed increased frequency from the beginning to the end of the spindle. The more intense the epilepsy is, the shorter are the durations of spindles of all types. The mean frequencies of `medium' and `fast' spindles were higher in rats with more intense signs of epilepsy. Overall, high epileptic activity in WAG/Rij rats was linked with significant changes in spindles of the transitional type, with less marked changes in the two traditionally identified types of spindle, slow and fast.
Epilepsy with myoclonic absences.
Manonmani, V; Wallace, S J
1994-01-01
The cases are described of eight children, five of them girls, who had epilepsy with myoclonic absences. The mean age of onset was 4.9 years. Brief episodes of loss of awareness with bilateral clonic jerking of the upper limbs were associated with rhythmic 3 cycles/second spike-wave discharges on electroencephalogram. Generalised tonic-clonic or astatic seizures, or both, also occurred in seven patients. All now have learning difficulties, and seven have behavioural problems. Conventional treatment for absences was effective in only two children. Of six patients treated with lamotrigine, five have improved substantially, but only one is in sustained complete remission. One recently diagnosed patient continues to have frequent myoclonic absences. As the response to treatment and long term outcome are much poorer, it is important to differentiate myoclonic absences from typical childhood absence epilepsy. PMID:8185360
Using recurrence plot for determinism analysis of EEG recordings in genetic absence epilepsy rats.
Ouyang, Gaoxiang; Li, Xiaoli; Dang, Chuangyin; Richards, Douglas A
2008-08-01
Understanding the transition of brain activity towards an absence seizure is a challenging task. In this paper, we use recurrence quantification analysis to indicate the deterministic dynamics of EEG series at the seizure-free, pre-seizure and seizure states in genetic absence epilepsy rats. The determinism measure, DET, based on recurrence plot, was applied to analyse these three EEG datasets, each dataset containing 300 single-channel EEG epochs of 5-s duration. Then, statistical analysis of the DET values in each dataset was carried out to determine whether their distributions over the three groups were significantly different. Furthermore, a surrogate technique was applied to calculate the significance level of determinism measures in EEG recordings. The mean (+/-SD) DET of EEG was 0.177+/-0.045 in pre-seizure intervals. The DET values of pre-seizure EEG data are significantly higher than those of seizure-free intervals, 0.123+/-0.023, (P<0.01), but lower than those of seizure intervals, 0.392+/-0.110, (P<0.01). Using surrogate data methods, the significance of determinism in EEG epochs was present in 25 of 300 (8.3%), 181 of 300 (60.3%) and 289 of 300 (96.3%) in seizure-free, pre-seizure and seizure intervals, respectively. Results provide some first indications that EEG epochs during pre-seizure intervals exhibit a higher degree of determinism than seizure-free EEG epochs, but lower than those in seizure EEG epochs in absence epilepsy. The proposed methods have the potential of detecting the transition between normal brain activity and the absence seizure state, thus opening up the possibility of intervention, whether electrical or pharmacological, to prevent the oncoming seizure.
Experimental Treatment Options in Absence Epilepsy.
Luijtelaar, Gilles van; Zobeiri, Mehrnoush; Lüttjohann, Annika; Depaulis, Antoine
2017-01-01
The benign character of absence epilepsy compared to other genetic generalized epilepsy syndromes has often hampered the search for new treatment options. Absence epilepsy is most often treated with ethosuximide or valproic acid. However, both drugs are not always well tolerated or fail, and seizure freedom for a larger proportion of patients remains to be achieved. The availability of genuine animal models of epilepsy does allow to search for new treatment options not only for absence epilepsy per se but also for other genetic - previously called idiopathic - forms of epilepsy. The recent discovery of a highly excitable cortical zone in these models is considered as a new therapeutic target area. Here, we provide an overview regarding the search for new therapeutical options as has been investigated in the genetic rodent models (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis can be achieved, various types of electrical and optogenetical invasive stimulations, different types of noninvasive stimulation and finally whether absence seizures can be predicted and prevented. Many factors determine either the cortical and or thalamic excitability or the interaction between cortex and thalamus and offer new possibilities for new anti-absence drugs, among others metabotropic glutamatergic positive and negative allosteric modulators. The inhibition of epileptogenesis by various drugs with its widespread consequences seems feasible, although its mechanisms remain obscure and seems different from the antiabsence action. Surgical intervention on the cortical zone initiating seizures, either with radiosurgery using synchrotron- generated microbeams, or ablation techniques might reduce spike-and-wave discharges in the rodent models. High frequency electrical subcortical or cortical stimulation might be a good way to abort ongoing spikeand- wave discharges. In addition, possibilities for prevention with real-time EEG analyses in combination with
Levetiracetam in Absence Epilepsy
ERIC Educational Resources Information Center
Verrotti, Alberto; Cerminara, Caterina; Domizio, Sergio; Mohn, Angelika; Franzoni, Emilio; Coppola, Giangennaro; Zamponi, Nelia; Parisi, Pasquale; Iannetti, Paola; Curatolo, Paolo
2008-01-01
The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty-one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrolment into…
Wireless system for long-term EEG monitoring of absence epilepsy
NASA Astrophysics Data System (ADS)
Whitchurch, Ashwin K.; Ashok, B. H.; Kumaar, R. V.; Saurkesi, K.; Varadan, Vijay K.
2002-11-01
Absence epilepsy is a form of epilepsy common mostly in children. The most common manifestations of Absence epilepsy are staring and transient loss of responsiveness. Also, subtle motor activities may occur. Due to the subtle nature of these symptoms, episodes of absence epilepsy may often go unrecognized for long periods of time or be mistakenly attributed to attention deficit disorder or daydreaming. Spells of absence epilepsy may last about 10 seconds and occur hundreds of times each day. Patients have no recollections of the events that occurred during those seizures and will resume normal activity without any postictal symptoms. The EEG during such episodes of Absence epilepsy shows intermittent activity of 3 Hz generalized spike and wave complexes. As EEG is the only way of detecting such symptoms, it is required to monitor the EEG of the patient for a long time and thus remain only in bed. So, effectively the EEG is being monitored only when the patient is stationary. The wireless monitoring sys tem described in this paper aims at eliminating this constraint and enables the physicial to monitor the EEG when the patient resumes his normal activities. This approach could even help the doctor identify possible triggers of absence epilepsy.
A role for the preoptic sleep-promoting system in absence epilepsy.
Suntsova, N; Kumar, S; Guzman-Marin, R; Alam, M N; Szymusiak, R; McGinty, D
2009-10-01
Absence epilepsy (AE) in humans and the genetic AE model in WAG/Rij rats are both associated with abnormalities in sleep architecture that suggest insufficiency of the sleep-promoting mechanisms. In this study we compared the functionality of sleep-active neuronal groups within two well-established sleep-promoting sites, the ventrolateral and median preoptic nuclei (VLPO and MnPN, respectively), in WAG/Rij and control rats. Neuronal activity was assessed using c-Fos immunoreactivity and chronic single-unit recording techniques. We found that WAG/Rij rats exhibited a lack of sleep-associated c-Fos activation of GABAergic MnPN and VLPO neurons, a lower percentage of MnPN and VLPO cells increasing discharge during sleep and reduced firing rates of MnPN sleep-active neurons, compared to non-epileptic rats. The role of sleep-promoting mechanisms in pathogenesis of absence seizures was assessed in non-epileptic rats using electrical stimulation and chemical manipulations restricted to the MnPN. We found that fractional activation of the sleep-promoting system in waking was sufficient to elicit absence-like seizures. Given that reciprocally interrelated sleep-promoting and arousal neuronal groups control thalamocortical excitability, we hypothesize that malfunctioning of sleep-promoting system results in impaired ascending control over thalamocortical rhythmogenic mechanisms during wake-sleep transitions thus favoring aberrant thalamocortical oscillations. Our findings suggest a pathological basis for AE-associated sleep abnormalities and a mechanism underlying association of absence seizures with wake-sleep transitions.
Childhood absence epilepsy successfully treated with the paleolithic ketogenic diet.
Clemens, Zsófia; Kelemen, Anna; Fogarasi, András; Tóth, Csaba
2013-12-01
Childhood absence epilepsy is an epilepsy syndrome responding relatively well to the ketogenic diet with one-third of patients becoming seizure-free. Less restrictive variants of the classical ketogenic diet, however, have been shown to confer similar benefits. Beneficial effects of high fat, low-carbohydrate diets are often explained in evolutionary terms. However, the paleolithic diet itself which advocates a return to the human evolutionary diet has not yet been studied in epilepsy. Here, we present a case of a 7-year-old child with absence epilepsy successfully treated with the paleolithic ketogenic diet alone. In addition to seizure freedom achieved within 6 weeks, developmental and behavioral improvements were noted. The child remained seizure-free when subsequently shifted toward a paleolithic diet. It is concluded that the paleolithic ketogenic diet was effective, safe and feasible in the treatment of this case of childhood absence epilepsy.
Dufour, Franck; Koning, Estelle; Nehlig, Astrid
2003-08-01
The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.
D’Amore, V.; Santolini, I.; van Rijn, C.M.; Biagioni, F.; Molinaro, G.; Prete, A.; Conn, P.J.; Lindsley, C.W.; Zhou, Y.; Vinson, P.N.; Rodriguez, A.L.; Jones, C.K.; Stauffer, S.R.; Nicoletti, F.; van Luijtelaar, G.; Ngomba, R.T.
2013-01-01
Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. PMID:22705340
Bauquier, Sebastien H; Lai, Alan; Jiang, Jonathan L; Sui, Yi; Cook, Mark J
2015-10-01
The aim of this prospective blinded study was to evaluate an automated algorithm for spike-and-wave discharge (SWD) detection applied to EEGs from genetic absence epilepsy rats from Strasbourg (GAERS). Five GAERS underwent four sessions of 20-min EEG recording. Each EEG was manually analyzed for SWDs longer than one second by two investigators and automatically using an algorithm developed in MATLAB®. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the manual (reference) versus the automatic (test) methods. The results showed that the algorithm had specificity, sensitivity, PPV and NPV >94%, comparable to published methods that are based on analyzing EEG changes in the frequency domain. This provides a good alternative as a method designed to mimic human manual marking in the time domain.
Citraro, Rita; Leo, Antonio; De Fazio, Pasquale; De Sarro, Giovambattista; Russo, Emilio
2015-01-01
Background and Purpose Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. Experimental Approach We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behaviour in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6-month-old) rats after a chronic 7 weeks treatment. Key Results ELTT with all antipsychotics did not affect the development of seizures, whereas, both ELTT haloperidol (1 mg·kg−1 day−1) and risperidone (0.5 mg·kg−1 day−1) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30 mg·kg−1 day−1) and duloxetine (10–30 mg·kg−1 day−1) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30 mg·kg−1 day−1 reduced immobility time while at 10 mg·kg−1 day−1 an increase was observed. Conclusions and Implications In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive-like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive-like behaviour. PMID
PICK1 uncoupling from mGluR7a causes absence-like seizures
Bertaso, Federica; Zhang, Chuansheng; Scheschonka, Astrid; de Bock, Frédéric; Fontanaud, Pierre; Marin, Philippe; Huganir, Richard L; Betz, Heinrich; Bockaert, Joël; Fagni, Laurent; Lerner-Natoli, Mireille
2009-01-01
Absence epilepsy is a neurological disorder that causes a recurrent loss of consciousness and generalized spike-and-wave discharges on an electroencephalogram (EEG). The role of metabotropic glutamate receptors (mGluRs) and associated scaffolding proteins in absence epilepsy has been unclear to date. We investigated a possible role for these proteins in absence epilepsy, focusing on the mGluR7a receptor and its PDZ-interacting protein, protein interacting with C kinase 1 (PICK1), in rats and mice. Injection of a cell-permeant dominant-negative peptide or targeted mutation of the mGluR7a C terminus, both of which disrupt the interaction between the receptor and PDZ proteins, caused behavioral symptoms and EEG discharges that are characteristic of absence epilepsy. Inactivation of the Pick1 gene also facilitated pharmacological induction of the absence epilepsy phenotype. The cortex and thalamus, which are known to participate in absence epilepsy, were involved, but the hippocampus was not. Our results indicate that disruption of the mGluR7a-PICK1 complex is sufficient to induce absence epilepsy—like seizures in rats and mice, thus providing, to the best of our knowledge, the first animal model of metabotropic glutamate receptor—PDZ protein interaction in absence epilepsy. PMID:18641645
Quantitative EEG analysis of the maturational changes associated with childhood absence epilepsy
NASA Astrophysics Data System (ADS)
Rosso, O. A.; Hyslop, W.; Gerlach, R.; Smith, R. L. L.; Rostas, J. A. P.; Hunter, M.
2005-10-01
This study aimed to examine the background electroencephalography (EEG) in children with childhood absence epilepsy, a condition whose presentation has strong developmental links. EEG hallmarks of absence seizure activity are widely accepted and there is recognition that the bulk of inter-ictal EEG in this group is normal to the naked eye. This multidisciplinary study aimed to use the normalized total wavelet entropy (NTWS) (Signal Processing 83 (2003) 1275) to examine the background EEG of those patients demonstrating absence seizure activity, and compare it with children without absence epilepsy. This calculation can be used to define the degree of order in a system, with higher levels of entropy indicating a more disordered (chaotic) system. Results were subjected to further statistical analyses of significance. Entropy values were calculated for patients versus controls. For all channels combined, patients with absence epilepsy showed (statistically significant) lower entropy values than controls. The size of the difference in entropy values was not uniform, with certain EEG electrodes consistently showing greater differences than others.
Spatiotemporal mapping of interictal epileptiform discharges in human absence epilepsy: A MEG study.
Rozendaal, Yvonne J W; van Luijtelaar, Gilles; Ossenblok, Pauly P W
2016-01-01
Although absence epilepsy is considered to be a prototypic type of generalized epilepsy, it is still under debate whether generalized 3 Hz spike-and-wave discharges (SWDs) might have a cortical focal origin. Here it is investigated whether focal interictal epileptiform discharges (IEDs), which typically occur in the electro- (EEG) and magnetoencephalogram (MEG) in case of focal epilepsy, are present in the MEG of children with absence epilepsy. Next, the location of the sources of the IEDs is established, and it is investigated whether the location is concordant to the earlier established focal cortical regions involved in the generalized SWDs of these children. Whole head MEG recordings of seven children with absence epilepsy were reviewed with respect to the presence of IEDs (spikes and sharp waves). These IEDs were grouped into distinct clusters, in which each contribution to a cluster yields a comparable magnetic field distribution. Source localization was then performed onto the average signal of each cluster using an equivalent current dipole model and a realistic head model of the cortical surface. IEDs were detected in 6 out of 7 patients. Source reconstruction indicated most often frontal, central or parietal origins of the IED in either the left and or right hemisphere. Spatiotemporal assessment of the IEDs indicated a stable location of the averages of these discharges, indicating a single underlying cortical source. The outcome of this pilot study shows that MEG is well suited for the detection of IEDs and suggests that their estimated sources coincide rather well with the cortical regions involved during the spikes of the SWDs. It is discussed whether the presence of IEDs, classically seen as a marker of focal epilepsies, indicate that absence epilepsy should be considered as a focal type of epilepsy, in which changes in the network are evolving rapidly. Copyright © 2015 Elsevier B.V. All rights reserved.
Evaluation of creative thinking in children with idiopathic epilepsy (absence epilepsy).
Di Filippo, T; Parisi, L; Roccella, M
2012-02-01
Creativity represents the silent character of human behaviour. In children with epilepsy, cognitive performance of has mainly been investigated under the assumption that the disorder represents a risk factor for the development of intellectual function. In subjects with different forms of epilepsy, neuropsychologic disorders have been detected even when cognitive-global functioning is unimpaired. The cognitive functions of subjects with epilepsy have been widely studied, but their creativity has been never evaluated to date. The aim of this study was to describe the development of creative thinking in a group of children with absence epilepsy. The test battery included: the Torrance Test of Creative Thinking (TTCT), the Wechsler Intelligence Scale for Children-revised (WISC-R) and the Goodenough Human Figure Drawing Test. Statistical analysis (Mann-Whitney test) showed a statistically significant difference (P <0.05) in test scores between two groups of subjects (children with epilesy vs control group), with higher scores for figure originality, figure fluidity and figure elaboration in the control group. There was a significant correlation (Spearman's rho) between verbal IQ and verbal fluidity and verbal flexibility subscale scores and between performance IQ and figure elaboration, between total IQ and verbal fluidity and verbal flexibility subscales (P <0.05; r >0.30). Low scores on the figure originality subscales seem to confirm the hypothesis that adverse psychodynamic and relational factors impoverish autonomy, flexibility and manipulator interests. The communication channels between subjects with epilepsy and their family members were affected by the disorder, as were the type of emotional dynamics and affective flux.
Frontal and temporal volumes in Childhood Absence Epilepsy.
Caplan, Rochelle; Levitt, Jennifer; Siddarth, Prabha; Wu, Keng Nei; Gurbani, Suresh; Sankar, Raman; Shields, W Donald
2009-11-01
This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child. The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ. These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.
Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.
Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale
2013-12-01
Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].
Learning skills and academic performance in children and adolescents with absence epilepsy.
Talero-Gutiérrez, C; Sánchez-Torres, J M; Velez-van-Meerbeke, A
2015-03-01
Although cognitive and learning disorders have been described in patients with epilepsy, very few studies focus on specific disorders such as absence epilepsy. The aim of this study was to evaluate learning skills and academic performance in children and adolescents with absence epilepsy. Observational case-control study. Cases were chosen from the Central League against Epilepsy's clinic in Bogotá, Colombia. Controls were selected from a private school and matched with cases by age, school year, and sex. Medical history, seizure frequency, antiepileptic treatment, and academic performance were assessed. Academic abilities were tested with Batería de Aptitudes Diferenciales y Generales (BADyG) (a Spanish-language test of differential and general aptitudes). Data were analysed using Student t-test. The sample consisted of 19 cases and 19 controls aged between 7 and 16. In 15 patients, seizures were controlled; all patients had received antiepileptic medication at some point and 78.9% were actively being treated. Although cases had higher rates of academic failure, a greater incidence of grade retention, and more therapeutic interventions than controls, these differences were not significant. Similarly, there were no significant differences on the BADyG test, except for the immediate memory subcategory on which cases scored higher than controls (P=.0006). Children treated pharmacologically for absence epilepsy, whose seizures are controlled, have normal academic abilities and skills for their age. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
Amygdala volumes in childhood absence epilepsy.
Schreibman Cohen, Ayelet; Daley, Melita; Siddarth, Prabha; Levitt, Jennifer; Loesch, Ingrid K; Altshuler, Lori; Ly, Ronald; Shields, W Donald; Gurbani, Suresh; Caplan, Rochelle
2009-11-01
Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses in childhood absence epilepsy (CAE), prompted this study of amygdala volume in CAE. Twenty-six children with CAE and 23 normal children, aged 6.6-15.8 years, underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala volumes were obtained by manual tracings. There were no significant amygdala volume differences between the CAE and normal groups. Within the CAE group, however, the children with ADHD had significantly smaller amygdala volumes than the subjects with CAE with no psychopathology and those with mood/anxiety diagnoses. There was also a significant relationship between higher seizure frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing development of the amygdala during late childhood and adolescence, despite the lack of significant group differences in amygdala volumes, the association of amygdala volume abnormalities with ADHD and seizure frequency implies a possible impact of the disorder on amygdala development and CAE-associated comorbidities, such as ADHD.
Powell, Kim L; Fitzgerald, Xavier; Shallue, Claire; Jovanovska, Valentina; Klugmann, Matthias; Von Jonquieres, Georg; O'Brien, Terence J; Morris, Margaret J
2018-05-01
Neuropeptide Y (NPY) is an important 36 amino acid peptide that is abundantly expressed in the mammalian CNS and is known to be an endogenous modulator of seizure activity, including in rat models of Genetic Generalised Epilepsy (GGE) with absence seizures. Studies have shown that viral-mediated "gene therapy" with overexpression of NPY in the hippocampus can suppress seizures in acquired epilepsy animal models. This study investigated whether NPY gene delivery to the thalamus or somatosensory cortex, using recombinant adeno-associated viral vector (rAAV), could produce sustained seizure suppression in the GAERS model of GGE with absence seizures. Three cohorts of GAERS were injected bilaterally into the thalamus (short term n = 14 and long term n = 8) or the somatosensory cortex (n = 26) with rAAV-NPY or rAAV-empty. EEG recordings were acquired weekly post-treatment and seizure expression was quantified. Anxiety levels were tested using elevated plus maze and open field test. NPY and NPY receptor mRNA and protein expression were evaluated using quantitative PCR, immunohistochemistry and immunofluorescence. Viral overexpression of human NPY in the thalamus and somatosensory cortex in GAERS significantly reduced the time spent in seizure activity and number of seizures, whereas seizure duration was only reduced after thalamic NPY overexpression. Human and rat NPY and rat Y2 receptor mRNA expression was significantly increased in the somatosensory cortex. NPY overexpression in the thalamus was observed in rAAV-NPY treated rats compared to controls in the long term cohort. No effect was observed on anxiety behaviour. We conclude that virally-mediated human NPY overexpression in the thalamus or somatosensory cortex produces sustained anti-epileptic effects in GAERS. NPY gene therapy may represent a novel approach for the treatment of patients with genetic generalised epilepsies. Copyright © 2018 Elsevier Inc. All rights reserved.
Attention impairment in childhood absence epilepsy: an impulsivity problem?
Cerminara, Caterina; D'Agati, Elisa; Casarelli, Livia; Kaunzinger, Ivo; Lange, Klaus W; Pitzianti, Mariabernarda; Parisi, Pasquale; Tucha, Oliver; Curatolo, Paolo
2013-05-01
Although attention problems have often been described in children with childhood absence epilepsy (CAE), the use of different methodological approaches, neuropsychological tests, and heterogeneous experimental groups has prevented identification of the selective areas of attention deficit in this population. In this study, we investigated several components of attention in children with CAE using a unique computerized test battery for attention performance. Participants included 24 patients with CAE and 24 controls matched for age and sex. They were tested with a computerized test battery, which included the following tasks: selective attention, impulsivity, focused attention, divided attention, alertness, and vigilance. Compared with healthy controls, patients with CAE made more commission errors in the Go/No-Go task and more omission errors in the divided attention task. Childhood absence epilepsy patients also showed decreased reaction times in measures of selective attention and a great variability of reaction times in alertness and Go/No-Go tasks. Our findings suggest that patients with CAE were impaired in tonic and phasic alertness, divided attention, selective attention, and impulsivity. Copyright © 2013 Elsevier Inc. All rights reserved.
Clinical dissection of early onset absence epilepsy in children and prognostic implications.
Agostinelli, Sergio; Accorsi, Patrizia; Beccaria, Francesca; Belcastro, Vincenzo; Canevini, Maria Paola; Capovilla, Giuseppe; Cappanera, Silvia; Dalla Bernardina, Bernardo; Darra, Francesca; Del Gaudio, Luigi; Elia, Maurizio; Falsaperla, Raffaele; Giordano, Lucio; Gobbi, Giuseppe; Minetti, Carlo; Nicita, Francesco; Parisi, Pasquale; Pavone, Piero; Pezzella, Marianna; Sesta, Michela; Spalice, Alberto; Striano, Salvatore; Tozzi, Elisabetta; Traverso, Monica; Vari, Stella; Vignoli, Aglaia; Zamponi, Nelia; Zara, Federico; Striano, Pasquale; Verrotti, Alberto
2013-10-01
To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Kirazlı, Özlem; Çavdar, Safiye; Yıldızel, Sercan; Onat, Filiz; Kaptanoğlu, Erkan
2017-02-01
An imbalance of GABAergic inhibition and glutamatergic excitation is suspected to be the cause of absence epileptic seizures. Absence seizures are known to be generated in thalamocortical circuitry. In the present study we used light microscopy immunohistochemistry to quantify the density of glutamate+ve neurons at two developmental stages (P10 and P60) in two thalamic nuclei, the ventrobasal (VB) and lateral geniculate nucleus (LGN) in Wistar rats and compared the results with similar data obtained from genetic absence epilepsy rats from Strasbourg (GAERS). Rats were perfused transcardially with glutaraldehyde and paraformaldehyde fixative, then samples from VB and LGN were removed from each animal and sectioned. The glutamatergic neurons were labelled using light-microscopic glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in VB and LGN of GAERS and Wistar rats. The data were statistically analyzed. The distribution of the glutamate+ve neurons in the VB thalamic nucleus showed a significant reduction in the neuronal profiles per unit thalamic area from P10 to P60 in both Wistar and GAERS. The decrease was greater in the GAERS compared to the Wistar animals. However, in the LGN no reduction was observed either in the Wistar or in the GAERS. Comparing the density of glutamate+ve neurons in the VB thalamic nucleus of P10 of Wistar animals with of P10 GAERS showed statistically significant greater densities of these neurons in GAERS than in the Wistar rats. However no significant difference was present at P60 between the Wistar and GAERS animals. The disproportional decrease in GAERS may be related to the onset of absence seizures or may be related to neurogenesis of absence epilepsy. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.
Kohmann, Denise; Lüttjohann, Annika; Seidenbecher, Thomas; Coulon, Philippe; Pape, Hans-Christian
2016-10-01
Gap junctional electrical coupling between neurons of the reticular thalamic nucleus (RTN) is critical for hypersynchrony in the thalamo-cortical network. This study investigates the role of electrical coupling in pathological rhythmogenesis in RTN neurons in a rat model of absence epilepsy. Rhythmic activation resulted in a Ca(2+) -dependent short-term depression (STD) of electrical coupling between pairs of RTN neurons in epileptic rats, but not in RTN of a non-epileptic control strain. Pharmacological blockade of gap junctions in RTN in vivo induced a depression of seizure activity. The STD of electrical coupling represents a mechanism of Ca(2+) homeostasis in RTN aimed to counteract excessive synchronization. Neurons in the reticular thalamic nucleus (RTN) are coupled by electrical synapses, which play a major role in regulating synchronous activity. This study investigates electrical coupling in RTN neurons from a rat model of childhood absence epilepsy, genetic absence epilepsy rats from Strasbourg (GAERS), compared with a non-epileptic control (NEC) strain, to assess the impact on pathophysiological rhythmogenesis. Whole-cell recordings were obtained from pairs of RTN neurons of GAERS and NEC in vitro. Coupling was determined by injection of hyperpolarizing current steps in one cell and monitoring evoked voltage responses in both activated and coupled cell. The coupling coefficient (cc) was compared under resting condition, during pharmacological interventions and repeated activation using a series of current injections. The effect of gap junctional coupling on seizure expression was investigated by application of gap junctional blockers into RTN of GAERS in vivo. At resting conditions, cc did not differ between GAERS and NEC. During repeated activation, cc declined in GAERS but not in NEC. This depression in cc was restored within 25 s and was prevented by intracellular presence of BAPTA in the activated but not in the coupled cell. Local application of
Sarrigiannis, Ptolemaios G; Zhao, Yifan; He, Fei; Billings, Stephen A; Baster, Kathleen; Rittey, Chris; Yianni, John; Zis, Panagiotis; Wei, Hualiang; Hadjivassiliou, Marios; Grünewald, Richard
2018-03-01
To determine the origin and dynamic characteristics of the generalised hyper-synchronous spike and wave (SW) discharges in childhood absence epilepsy (CAE). We applied nonlinear methods, the error reduction ratio (ERR) causality test and cross-frequency analysis, with a nonlinear autoregressive exogenous (NARX) model, to electroencephalograms (EEGs) from CAE, selected with stringent electro-clinical criteria (17 cases, 42 absences). We analysed the pre-ictal and ictal strength of association between homologous and heterologous EEG derivations and estimated the direction of synchronisation and corresponding time lags. A frontal/fronto-central onset of the absences is detected in 13 of the 17 cases with the highest ictal strength of association between homologous frontal followed by centro-temporal and fronto-central areas. Delays consistently in excess of 4 ms occur at the very onset between these regions, swiftly followed by the emergence of "isochronous" (0-2 ms) synchronisation but dynamic time lag changes occur during SW discharges. In absences an initial cortico-cortical spread leads to dynamic lag changes to include periods of isochronous interhemispheric synchronisation, which we hypothesize is mediated by the thalamus. Absences from CAE show ictal epileptic network dynamics remarkably similar to those observed in WAG/Rij rats which guided the formulation of the cortical focus theory. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
Interictal cardiorespiratory variability in temporal lobe and absence epilepsy in childhood.
Varon, Carolina; Montalto, Alessandro; Jansen, Katrien; Lagae, Lieven; Marinazzo, Daniele; Faes, Luca; Van Huffel, Sabine
2015-04-01
It is well known that epilepsy has a profound effect on the autonomic nervous system, especially on the autonomic control of heart rate and respiration. This effect has been widely studied during seizure activity, but less attention has been given to interictal (i.e. seizure-free) activity. The studies that have been done on this topic, showed that heart rate and respiration can be affected individually, even without the occurrence of seizures. In this work, the interactions between these two individual physiological variables are analysed during interictal activity in temporal lobe and absence epilepsy in childhood. These interactions are assessed by decomposing the predictive information about heart rate variability, into different components like the transfer entropy, cross-entropy, self- entropy and the conditional self entropy. Each one of these components quantifies different types of shared information. However, when using the cross-entropy and the conditional self entropy, it is possible to split the information carried by the heart rate, into two main components, one related to respiration and one related to different mechanisms, like sympathetic activation. This can be done after assuming a directional link going from respiration to heart rate. After analysing all the entropy components, it is shown that in subjects with absence epilepsy the information shared by respiration and heart rate is significantly lower than for normal subjects. And a more remarkable finding indicates that this type of epilepsy seems to have a long term effect on the cardiac and respiratory control mechanisms of the autonomic nervous system.
Ictal connectivity in childhood absence epilepsy: Associations with outcome.
Tenney, Jeffrey R; Kadis, Darren S; Agler, William; Rozhkov, Leonid; Altaye, Mekibib; Xiang, Jing; Vannest, Jennifer; Glauser, Tracy A
2018-05-01
The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)-functional magnetic resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response. Sixteen children with newly diagnosed and drug-naive CAE had 31 typical absence seizures during EEG-fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event-related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG-effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)-treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response. Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (P < .05). Pretreatment ictal connectivity differences in children with CAE were associated with response to antiepileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.
de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Lopim, Glauber Menezes; Vannucci Campos, Diego; Fernandes, Jansen; Cabral, Francisco Romero; Arida, Ricardo Mario
2017-04-01
Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.
Pretreatment seizure semiology in childhood absence epilepsy.
Kessler, Sudha Kilaru; Shinnar, Shlomo; Cnaan, Avital; Dlugos, Dennis; Conry, Joan; Hirtz, Deborah G; Hu, Fengming; Liu, Chunyan; Mizrahi, Eli M; Moshé, Solomon L; Clark, Peggy; Glauser, Tracy A
2017-08-15
To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern. Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome. © 2017 American Academy of Neurology.
NASA Astrophysics Data System (ADS)
Sysoeva, Marina V.; Kuznetsova, Galina D.; van Rijn, Clementina M.; Sysoev, Ilya V.
2016-04-01
WAG/Rij rats are well known genetic model of absence epilepsy, which is traditionally considered as a nonconvulsive generalised epilepsy of unknown aetiology. In current study the effect of (R)-(+)-WIN 55,212-2 (cannabis agonist) injection on the coupling between different parts of cortex was studied on 27 male 8 month old rats using local field potentials. Recently developed non-linear adapted Granger causality approach was used as a primary method. It was shown that first 2 hours after the injection the coupling between most channel pairs rises in comparison with the spontaneous activity, whilst long after the injection (2-6 hours) it drops down. The coupling increase corresponds to the mentioned before treatment effect, when the number and the longitude of seizures significantly decreases. However the subsequent decrease of the coupling in the cortex is accompanied by the dramatic increase of the longitude and the number of seizures. This assumes the hypothesis that a relatively higher coupling in the cortical network can prevent the seizure propagation and generalisation.
Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...
Viscum Album in the Treatment of a Girl With Refractory Childhood Absence Epilepsy.
von Schoen-Angerer, Tido; Madeleyn, René; Kienle, Gunver; Kiene, Helmut; Vagedes, Jan
2015-07-01
Viscum album (European mistletoe) extracts have known immunomodulatory effects but little data exist on anticonvulsant activity despite its usefulness having been reported for centuries. A 4½-year-old girl with childhood absence epilepsy and global developmental delay was treated with different antiepileptic drugs and ketogenic diet but failed to become seizure free over a 2-year period. She also received different herbal remedies as part of an integrative medicine approach. Initial improvement occurred on valproate-ethosuximide, a further improvement was seen after adding clobazam to valproate. Final cessation of absence activity occurred after a dose increase of V album. She was still seizure free at the 12-month follow-up. V album appears to have been a necessary adjunct treatment for this child to become seizure free. We call on physicians to report their experiences of V album in epilepsy and suggest further study. © The Author(s) 2014.
Neurofibromin Regulates Seizure Attacks in the Rat Pilocarpine-Induced Model of Epilepsy.
Ren, Min; Li, Kunyi; Wang, Dan; Guo, Jiamei; Li, Jing; Yang, Guang; Long, Xianghua; Shen, Wenjing; Hu, Rong; Wang, Xuefeng; Zeng, Kebin
2016-11-01
Studies have shown that neurofibromin (NF1) restricts GABA release at inhibitory synapses and regulates dendritic spine formation, which may play an important role in temporal lobe epilepsy (TLE). NF1 expression was detected by double-label immunofluorescence, immunohistochemistry, and western blot analysis in the brains of pilocarpine-induced epilepsy model rats at 6 h, 24 h, 72 h, 7 days, 14 days, 30 days, and 60 days after kindling. NF1 was localized primarily in the nucleus and cytoplasm of neurons. NF1 protein levels significantly increased in the chronic phase (from 7 days until 60 days) in this epileptic rat model. After NF1 expression was knocked down by specific siRNA, the effects of kindling with pilocarpine were evaluated on the 7th day after kindling. The onset latencies of pilocarpine-induced seizures were elevated, and the seizure frequency and duration were reduced in these rats. Our study demonstrates that NF1 promoted seizure attacks in rats with pilocarpine-induced epilepsy.
Zhang, Yanke; Gao, Baobing; Xiong, Yan; Zheng, Fangshuo; Xu, Xin; Yang, Yong; Hu, Yida; Wang, Xuefeng
2017-07-01
SH3 and multiple ankyrin (ANK) repeat domain 3 (SHANK3) is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. SHANK3 plays an important role in the formation and maturation of excitatory synapses. In the brain, SHANK3 directly or indirectly interacts with various synaptic molecules including N-methyl-D-aspartate receptor, the metabotropic glutamate receptor (mGluR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Previous studies have shown that Autism spectrum disorder is a result of mutations of the main SHANK3 isoforms, which may be due to deficit in excitatory synaptic transmission and plasticity. Recently, accumulating evidence has demonstrated that overexpression of SHANK3 could induce seizures in vivo. However, little is known about the role of SHANK3 in refractory temporal lobe epilepsy (TLE). Therefore, we investigated the expression pattern of SHANK3 in patients with intractable temporal lobe epilepsy and in pilocarpine-induced models of epilepsy. Immunofluorescence, immunohistochemistry, and western blot analysis were used to locate and determine the expression of SHANK3 in the temporal neocortex of patients with epilepsy, and in the hippocampus and temporal lobe cortex of rats in a pilocarpine-induced epilepsy model. Double-labeled immunofluorescence showed that SHANK3 was mainly expressed in neurons. Western blot analysis confirmed that SHANK3 expression was increased in the neocortex of TLE patients and rats. These results indicate that SHANK3 participates in the pathology of epilepsy.
Ma, Limin; Li, Ruohan; Huang, Hao; Yuan, Jinxian; Ou, Shu; Xu, Tao; Yu, Xinyuan; Liu, Xi; Chen, Yangmei
2017-05-01
Some studies have suggested that BAFF and BAFFR are highly expressed in the central nervous system (CNS) and participate in inflammatory and immune associated diseases. However, whether BAFF and BAFFR are involved in the pathogenesis of epilepsy remains unknown. This study aimed to investigate the expression of BAFF and BAFFR proteins in the brains of patients with temporal lobe epilepsy (TLE) and in a pilocarpine-induced rat model of TLE to identify possible roles of the BAFF-BAFFR signaling pathway in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot, immunohistochemistry, and double-immunofluorescence were performed in this study. The results showed that BAFF and BAFFR expression levels were markedly up-regulated in intractable TLE patients and TLE rats. Moreover, BAFF and BAFFR proteins mainly highly expressed in the membranes and cytoplasms of the dendritic marker MAP2 in the cortex and hippocampus. Therefore, the significant increased in BAFF and BAFFR protein expression in both TLE patients and rats suggest that BAFF and BAFFR may play important roles in regulating the pathogenesis of epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Reif, P S; Männer, A; Willems, L M; Kay, L; Zöllner, J P; Klein, K M; Rosenow, F; Strzelczyk, A
2018-04-06
Nearly 10 years after its introduction into the market, the significance of lacosamide in genetic generalized epilepsies is still unclear. Its new mode of action may qualify lacosamide as a therapeutic agent in this entity, but only a limited number of cases have been published so far. To describe the efficacy of lacosamide as treatment in a patient with the absence status epilepticus. We report on a 28-year-old woman with genetic generalized epilepsy who suffered recurrent absence status epilepticus during video-EEG-monitoring. After treatment failure of first- and second-line medication, lacosamide was administered. The outcome in this patient was evaluated, and a systematic literature review was performed for the use of lacosamide in the absence status epilepticus. After application of 400 mg lacosamide intravenously, the absence status epilepticus terminated within 30 minutes. No further seizures or epileptiform discharges reoccurred until the end of video-EEG-Monitoring 3 days later. The role of lacosamide as a therapeutic option in patients with the absence status epilepticus is unclear. Only two cases have been reported so far with conflicting results. Further randomized controlled studies are required to validate the relevance of lacosamide as treatment for status epilepticus in genetic generalized and the absence epilepsy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Blik, Vitaliya
2015-01-01
Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.
Unraveling Genetic Modifiers in the Gria4 Mouse Model of Absence Epilepsy
Frankel, Wayne N.; Mahaffey, Connie L.; McGarr, Tracy C.; Beyer, Barbara J.; Letts, Verity A.
2014-01-01
Absence epilepsy (AE) is a common type of genetic generalized epilepsy (GGE), particularly in children. AE and GGE are complex genetic diseases with few causal variants identified to date. Gria4 deficient mice provide a model of AE, one for which the common laboratory inbred strain C3H/HeJ (HeJ) harbors a natural IAP retrotransposon insertion in Gria4 that reduces its expression 8-fold. Between C3H and non-seizing strains such as C57BL/6, genetic modifiers alter disease severity. Even C3H substrains have surprising variation in the duration and incidence of spike-wave discharges (SWD), the characteristic electroencephalographic feature of absence seizures. Here we discovered extensive IAP retrotransposition in the C3H substrain, and identified a HeJ-private IAP in the Pcnxl2 gene, which encodes a putative multi-transmembrane protein of unknown function, resulting in decreased expression. By creating new Pcnxl2 frameshift alleles using TALEN mutagenesis, we show that Pcnxl2 deficiency is responsible for mitigating the seizure phenotype – making Pcnxl2 the first known modifier gene for absence seizures in any species. This finding gave us a handle on genetic complexity between strains, directing us to use another C3H substrain to map additional modifiers including validation of a Chr 15 locus that profoundly affects the severity of SWD episodes. Together these new findings expand our knowledge of how natural variation modulates seizures, and highlights the feasibility of characterizing and validating modifiers in mouse strains and substrains in the post-genome sequence era. PMID:25010494
Williams, Mark S.; Altwegg‐Boussac, Tristan; Chavez, Mario; Lecas, Sarah; Mahon, Séverine
2016-01-01
Key points Absence seizures are accompanied by spike‐and‐wave discharges in cortical electroencephalograms. These complex paroxysmal activities, affecting the thalamocortical networks, profoundly alter cognitive performances and preclude conscious perception.Here, using a well‐recognized genetic model of absence epilepsy, we investigated in vivo how information processing was impaired in the ictogenic neurons, i.e. the population of cortical neurons responsible for seizure initiation.In between seizures, ictogenic neurons were more prone to generate bursting activity and their firing response to weak depolarizing events was considerably facilitated compared to control neurons.In the course of seizures, information processing became unstable in ictogenic cells, alternating between an increased and a decreased responsiveness to excitatory inputs, depending on the spike and wave patterns.The state‐dependent modulation in the excitability of ictogenic neurons affects their inter‐seizure transfer function and their time‐to‐time responsiveness to incoming inputs during absences. Abstract Epileptic seizures result from aberrant cellular and/or synaptic properties that can alter the capacity of neurons to integrate and relay information. During absence seizures, spike‐and‐wave discharges (SWDs) interfere with incoming sensory inputs and preclude conscious experience. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well‐established animal model of absence epilepsy, allows exploration of the cellular basis of this impaired information processing. Here, by combining in vivo electrocorticographic and intracellular recordings from GAERS and control animals, we investigated how the pro‐ictogenic properties of seizure‐initiating cortical neurons modify their integrative properties and input–output operation during inter‐ictal periods and during the spike (S‐) and wave (W‐) cortical patterns alternating during seizures. In addition to a
Cognitive impairment and spontaneous epilepsy in rats with malformations of cortical development.
Ye-wei, Xiao; Rong, Wang; Xun-tai, Ma; Shan, Zhang; Qian, Chen; Shi-hua, Huang; Fu-qun, Mao; Xiao-ming, Xiong
2015-12-01
To examine the cognition, spontaneous epilepsy, and electroencephalography (EEG) characteristics of rats with malformations of cortical development (MCD) and their use as an animal model for investigating the pathogenesis of intractable epilepsy and screening novel antiepileptic drugs. An epileptic rat model of MCD was established with the F1 generation of pregnant rats after X-irradiation with 175 cGy (Group L), 195 cGy (Group M), or 215 cGy (Group H). Long-term video-EEG monitoring was used to record the seizures in the rats with MCD. Cognition was assessed with the Morris water maze. The EEGs were recorded and analyzed in the frontal and parietal lobes and hippocampi of adult rats. Finally, the brain tissues were processed for Nissl staining. The model groups exhibited markedly prolonged escape latencies and distinct decrements in the percent distance traveled in the target quadrant and platform-crossing frequency. These findings were dose-dependent. Frequent interictal epileptiform discharges were observed in the frontal and parietal lobes and hippocampi of adult rats, and their incidences were markedly higher in the model groups compared with that in the normal controls, with Group M having the highest incidence. Spontaneous seizures were observed in the model groups (mean incidence, 46.7%). The daily mean frequency of seizures and the incidence of spontaneous seizures were highest in Group M. Nissl staining revealed a dose-dependent pattern of hippocampal abnormalities, cortical and subcortical nodular heterotopia, and callosal agenesis in the model groups. The 195 cGy dose was most appropriate for establishing an epileptic model of MCD with X-irradiation. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Neuronal zinc-α2-glycoprotein is decreased in temporal lobe epilepsy in patients and rats.
Liu, Ying; Wang, Teng; Liu, Xi; Wei, Xin; Xu, Tao; Yin, Maojia; Ding, Xueying; Mo, Lijuan; Chen, Lifen
2017-08-15
Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used. The existence and level of ZAG in the brain were identified using immunohistochemistry, double-labeled immunofluorescence and western blot, and the expression level of AZGP1 mRNA was determined with quantitative real-time polymerase chain reaction (qrt-PCR). To explore the potential biological role of ZAG in the brain, co-immunoprecipitation (Co-IP) of phosphorylated ERK (p-ERK), TGF-β1 and ZAG was also performed. ZAG was found in the cytoplasm of neurons in brain tissue from both patients and rats. The levels of AZGP1 mRNA and ZAG were lower in refractory TLE patients and PTZ-kindled rats than in controls. In addition, the ZAG level decreased as PTZ kindling continued. Co-IP identified direct binding between p-ERK, TGF-β1 and ZAG. ZAG was found to be synthesized in neurons, and both the AZGP1 mRNA and ZAG protein levels were decreased in epilepsy patients and rat models. The reduction in ZAG may participate in the pathogenesis and pathophysiology of epilepsy by interacting with p-ERK and TGF-β1, promoting inflammation, regulating the metabolism of ketone bodies, or affecting other epilepsy-related molecules. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Bagshaw, Andrew P; Rollings, David T; Khalsa, Sakh; Cavanna, Andrea E
2014-01-01
The link between epilepsy and sleep is well established on many levels. The focus of the current review is on recent neuroimaging investigations into the alterations of consciousness that are observed during absence seizures and the descent into sleep. Functional neuroimaging provides simultaneous cortical and subcortical recording of activity throughout the brain, allowing a detailed definition and characterization of large-scale brain networks and the interactions between them. This has led to the identification of a set of regions which collectively form the consciousness system, which includes contributions from the default mode network (DMN), ascending arousal systems, and the thalamus. Electrophysiological and neuroimaging investigations have also clearly demonstrated the importance of thalamocortical and corticothalamic networks in the evolution of sleep and absence epilepsy, two phenomena in which the subject experiences an alteration to the conscious state and a disconnection from external input. However, the precise relationship between the consciousness system, thalamocortical networks, and consciousness itself remains to be clarified. One of the fundamental challenges is to understand how distributed brain networks coordinate their activity in order to maintain and implement complex behaviors such as consciousness and how modifications to this network activity lead to alterations in consciousness. By taking into account not only the level of activation of individual brain regions but also their connectivity within specific networks and the activity and connectivity of other relevant networks, a more specific quantification of brain states can be achieved. This, in turn, may provide a more fundamental understanding of the alterations to consciousness experienced in sleep and epilepsy. © 2013.
Inoue, Y; Mihara, T; Matsuda, K; Tottori, T; Otsubo, T; Yagi, K
2000-02-01
The diagnostic and prognostic significance of the absence of simple partial seizures (SPS) immediately preceding complex partial seizures (CPS) was examined in patients with temporal lobe epilepsy. The status of self-reported SPS in 193 patients with temporal lobe epilepsy who had surgical therapy more than 2 years ago was reviewed. Before surgery, 37 patients never experienced SPS before CPS (Group A), 156 patients either always or occasionally had SPS before CPS (Group B). The frequency of mesial temporal sclerosis (MTS) was lower and the age at onset of epilepsy was higher in Group A. The seizure focus was in the language-dominant temporal lobe in 73% of the cases in Group A, compared with 40% in Group B. The surgical outcome did not differ between the two groups. The findings suggest that temporal lobe seizures without preceding SPS tend to originate in the language-dominant temporal lobe that contains a pathologic etiology other than MTS, especially in the lateral temporal lobe. The surgical outcome in patients without SPS is similar to that in patients with SPS.
Medel-Matus, Jesús-Servando; Shin, Don; Sankar, Raman; Mazarati, Andrey
2017-08-01
The objective was to determine whether the depression comorbid with epilepsy could be predicted based on inherent premorbid patterns of monoaminergic transmission. In male Wistar rats, despair-like and anhedonia-like behaviors were examined using forced swimming and taste preference tests, respectively. Serotonergic raphe nucleus (RN)-prefrontal cortex (PFC) and dopaminergic ventral tegmental area (VTA)-nucleus accumbens (NAcc) pathways were interrogated by fast scan cyclic voltammetry (FSCV). The assays were performed before and 2 months after pilocarpine status epilepticus. In a subset of naive rats, FSCV, coupled with the intensity-dependent stimulation paradigm, detected specific deviations in each pathway (six rats for RN-PFC and seven rats for VTA-NAcc, with overlap in two, of 19 total subjects) in the absence of behavioral impairments. During epilepsy, animals with preexisting deviations in RN-PFC invariably developed despair, and rats with deviations in VTA-NAcc developed anhedonia. Serotonergic and dopaminergic pathways, respectively, showed signs of explicit deterioration. We suggest that epilepsy triggers decompensations in the already vulnerable depression-relevant neuronal circuits, which culminate in depression. The established connection between the identified specific signatures in monoamine transmission in naive rats and specific symptoms of epilepsy-associated depression may help in understanding causes of comorbidity and in developing its early biomarkers. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Sysoeva, Marina V; Vinogradova, Lyudmila V; Kuznetsova, Galina D; Sysoev, Ilya V; van Rijn, Clementina M
2016-11-01
Spike-and-wave discharges (SWDs) recorded in the cortical EEGs of WAG/Rij rats are the hallmark for absence epilepsy in this model. Although this type of epilepsy was long regarded as a form of primary generalized epilepsy, it is now recognized that there is an initiation zone - the perioral region of the somatosensory cortex. However, networks involved in spreading the seizure are not yet fully known. Previously, the dynamics of coupling between different layers of the perioral cortical region and between these zones and different thalamic nuclei was studied in time windows around the SWDs, using nonlinear Granger causality. The aim of the present study was to investigate, using the same method, the coupling dynamics between different regions of the cortex and between these regions and the hippocampus. Local field potentials were recorded in the frontal, parietal, and occipital cortices and in the hippocampus of 19 WAG/Rij rats. To detect changes in coupling reliably in a short time window, in order to provide a good temporal resolution, the innovative adapted time varying nonlinear Granger causality method was used. Mutual information function was calculated in addition to validate outcomes. Results of both approaches were tested for significance. The SWD initiation process was revealed as an increase in intracortical interactions starting from 3.5s before the onset of electrographic seizure. The earliest preictal increase in coupling was directed from the frontal cortex to the parietal cortex. Then, the coupling became bidirectional, followed by the involvement of the occipital cortex (1.5s before SWD onset). There was no driving from any cortical region to hippocampus, but a slight increase in coupling from hippocampus to the frontoparietal cortex was observed just before SWD onset. After SWD onset, an abrupt drop in coupling in all studied pairs was observed. In most of the pairs, the decoupling rapidly disappeared, but driving force from hippocampus and
Danhofer, Pavlína; Brázdil, Milan; Ošlejšková, Hana; Kuba, Robert
2014-06-01
The study aim was to evaluate pharmacotherapy effects and long-term seizure outcomes in patients with juvenile absence epilepsy (JAE) during a five-year follow-up period. The secondary aim was to identify factors from patient history and determine their influence on seizure control. We retrospectively studied 46 patients with JAE in the period between 2006 and 2011. The age at seizure onset, onset seizure type, family history of epilepsy, status epilepticus in history, medication history, and the rate of seizure control were studied. There were 30 females (65.2%) and 16 males (34.8%) in the study. The mean age at seizure onset was 12.9±5.6 years (ranged from 3 to 28 years). In 30 patients (65.2%), seizure onset was with absences, in 15 patients (32.6%) with generalized tonic-clonic seizure (GTCS), and in 1 patient (2.2%) with absence status. In 43 patients (93.5%), GTCS occurred in the course of the disease. Family history for epilepsy was positive in 10 patients (21.7%). In the five-year follow-up period, seizure freedom (Group 1) was achieved in 7 patients (15.2%). In total, 22 patients (47.8%) were classified into the groups involving very poor seizure control and antiepileptic drug resistance (Groups 5 and 6). The mean number of antiepileptic drugs (AEDs) used in the course of the disease in appropriate therapeutic doses was 3.8±2.3 (1-10 AEDs). The study results show that almost half of JAE patients have poor seizure control with a high rate of pharmacoresistance. The outcome of JAE can be very uncertain. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Dezsi, Gabi; Ozturk, Ezgi; Salzberg, Michael R; Morris, Margaret; O'Brien, Terence J; Jones, Nigel C
2016-09-01
The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Environmental enrichment produces disease-modifying effects on genetically determined absence epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for genetically determined epilepsy which may benefit subsequent generations. Copyright © 2016 Elsevier Inc. All rights reserved.
Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino Glaxo Rijswijk rats.
Lakatos, Renáta Krisztina; Dobolyi, Árpád; Kovács, Zsolt
2018-05-01
Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the activity of xanthine oxidase, by which allopurinol inhibits catabolism of hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level of uric acid. Although the modulation of serum uric acid level is a widely used strategy in the treatment of certain diseases, our knowledge regarding the effects of uric acid on epileptic activity is far from complete. Thus, the main aim of this study was the investigation of the effect of uric acid on absence epileptic seizures (spike-wave discharges: SWDs) in a model of human absence epilepsy, the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. We investigated the influence of intraperitoneally (i.p.) injected uric acid (100 mg/kg and 200 mg/kg), allopurinol (50 mg/kg and 100 mg/kg), a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) and inosine (500 mg/kg) alone and the combined application of allopurinol (50 mg/kg) with uric acid (100 mg/kg) or inosine (500 mg/kg) as well as indomethacin (10 mg/kg) with uric acid (100 mg/kg) and inosine (500 mg/kg) with uric acid (100 mg/kg) on absence epileptic activity. We demonstrated that both uric acid and allopurinol alone significantly increased the number of SWDs whereas indomethacin abolished the uric acid-evoked increase in SWD number. Our results suggest that uric acid and allopurinol have proepileptic effects in WAG/Rij rats. Copyright © 2018 Elsevier B.V. All rights reserved.
Toyoda, Izumi; Bower, Mark R.; Leyva, Fernando
2013-01-01
Temporal lobe epilepsy is the most common form of epilepsy in adults. The pilocarpine-treated rat model is used frequently to investigate temporal lobe epilepsy. The validity of the pilocarpine model has been challenged based largely on concerns that seizures might initiate in different brain regions in rats than in patients. The present study used 32 recording electrodes per rat to evaluate spontaneous seizures in various brain regions including the septum, dorsomedial thalamus, amygdala, olfactory cortex, dorsal and ventral hippocampus, substantia nigra, entorhinal cortex, and ventral subiculum. Compared with published results from patients, seizures in rats tended to be shorter, spread faster and more extensively, generate behavioral manifestations more quickly, and produce generalized convulsions more frequently. Similarities to patients included electrographic waveform patterns at seizure onset, variability in sites of earliest seizure activity within individuals, and variability in patterns of seizure spread. Like patients, the earliest seizure activity in rats was recorded most frequently within the hippocampal formation. The ventral hippocampus and ventral subiculum displayed the earliest seizure activity. Amygdala, olfactory cortex, and septum occasionally displayed early seizure latencies, but not above chance levels. Substantia nigra and dorsomedial thalamus demonstrated consistently late seizure onsets, suggesting their unlikely involvement in seizure initiation. The results of the present study reveal similarities in onset sites of spontaneous seizures in patients with temporal lobe epilepsy and pilocarpine-treated rats that support the model's validity. PMID:23825415
Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy.
D’Amour, James; Magagna-Poveda, Alejandra; Moretto, Jillian; Friedman, Daniel; LaFrancois, John J.; Pearce, Patrice; Fenton, Andre A.; MacLusky, Neil J.; Scharfman, Helen E.
2015-01-01
In catamenial epilepsy, seizures exhibit a cyclic pattern that parallels the menstrual cycle. Many studies suggest that catamenial seizures are caused by fluctuations in gonadal hormones during the menstrual cycle, but this has been difficult to study in rodent models of epilepsy because the ovarian cycle in rodents, called the estrous cycle, is disrupted by severe seizures. Thus, when epilepsy is severe, estrous cycles become irregular or stop. Therefore, we modified kainic acid (KA)- and pilocarpine-induced status epilepticus (SE) models of epilepsy so that seizures were rare for the first months after SE, and conducted video-EEG during this time. The results showed that interictal spikes (IIS) occurred intermittently. All rats with regular 4-day estrous cycles had IIS that waxed and waned with the estrous cycle. The association between the estrous cycle and IIS was strong: if the estrous cycles became irregular transiently, IIS frequency also became irregular, and when the estrous cycle resumed its 4-day pattern, IIS frequency did also. Furthermore, when rats were ovariectomized, or males were recorded, IIS frequency did not show a 4-day pattern. Systemic administration of an estrogen receptor antagonist stopped the estrous cycle transiently, accompanied by transient irregularity of the IIS pattern. Eventually all animals developed severe, frequent seizures and at that time both the estrous cycle and the IIS became irregular. We conclude that the estrous cycle entrains IIS in the modified KA and pilocarpine SE models of epilepsy. The data suggest that the ovarian cycle influences more aspects of epilepsy than seizure susceptibility. PMID:25864929
Mao, Ke; You, Chao; Lei, Ding; Zhang, Heng
2015-01-01
The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy. The chronic epilepsy rat model was prepared by intraperitoneally injecting pentylenetetrazole to the rats pre-treated with CBD (10, 20 and 50 mg/kg) for 28 consecutive days. Behavioral measurements of convulsion following pentylenetetrazole treatment and morphological changes of the hippocampal neurons with hematoxylin and eosin staining were used to observe the epileptic behaviour. Immunohistochemistry was used to detect the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus. The mRNA expression of N-methyl-D-aspartic acid (NMDA) receptor subunits (NR1 and NR2B) was detected by reverse transcription polymerase chain reaction. The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg). The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased. CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly. Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy. PMID:26309534
Mao, Ke; You, Chao; Lei, Ding; Zhang, Heng
2015-01-01
The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy. The chronic epilepsy rat model was prepared by intraperitoneally injecting pentylenetetrazole to the rats pre-treated with CBD (10, 20 and 50 mg/kg) for 28 consecutive days. Behavioral measurements of convulsion following pentylenetetrazole treatment and morphological changes of the hippocampal neurons with hematoxylin and eosin staining were used to observe the epileptic behaviour. Immunohistochemistry was used to detect the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus. The mRNA expression of N-methyl-D-aspartic acid (NMDA) receptor subunits (NR1 and NR2B) was detected by reverse transcription polymerase chain reaction. The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg). The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased. CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly. Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.
Microsensors and wireless system for monitoring epilepsy
NASA Astrophysics Data System (ADS)
Whitchurch, Ashwin K.; Ashok, B. H.; Kumaar, Raman V.; Sarukesi, K.; Jose, K. A.; Varadan, Vijay K.
2003-07-01
Epilepsy is a form of brain disorder caused by abnormal discharges of neurons. The most common manifestations of epilepsy are seizures which could affect visual, aural and motor abilities of a person. Absence epilepsy is a form of epilepsy common mostly in children. The most common manifestations of absence epilepsy are staring and transient loss of responsiveness. Also, subtle motor activities may occur. Due to the subtle nature of these symptoms, episodes of absence epilepsy may often go unrecognized for long periods of time or be mistakenly attributed to attention deficit disorder or daydreaming. Spells of absence epilepsy may last about 10 seconds and occur hundreds of times each day. Patients have no recollections of the events occurred during those seizures and will resume normal activity without any postictal symptoms. The EEG during such episodes of Absence epilepsy shows intermittent activity of 3 Hz generalized spike and wave complexes. As EEG is the only way of detecting such symptoms, it is required to monitor the EEG of the patient for a long time, usually the whole day. This requires that the patient be connected to the EEG recorder all the time and thus remain only in the bed. So, effectively the EEG is being monitored only when the patient is stationary. The wireless monitoring system described in this paper aims at eliminating this constraint and enables the physician to monitor the EEG when the patient resumes his normal activities. This approach could even help the doctor identify possible triggers of absence epilepsy.
Nejm, Mariana Bocca; Haidar, André Abou; Hirata, Aparecida Emiko; Oyama, Lila Missae; de Almeida, Antonio-Carlos Guimarães; Cysneiros, Roberta Monterazzo; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Scorza, Fulvio Alexandre
2017-01-01
Sudden unexpected death in epilepsy (SUDEP) is a major cause of premature death related to epilepsy. The causes of SUDEP remain unknown, but cardiac arrhythmias and asphyxia have been suggested as a major mechanism of this event. Inflammation has been implicated in the pathogenesis of both epilepsy and ventricular arrhythmia, with interleukin-6 (IL-6) being recognized as a crucial orchestrator of inflammatory states. Our group previously reported that levels of IL-6 were increased in the hearts of epileptic rats. In this scenario, anti-inflammatory actions are among the beneficial effects of fish oil dietary supplementation. This investigation revealed that elevated levels of IL-6 in the heart were markedly reduced in epileptic rats that were treated in the long-term with fish oil, suggesting protective anti-inflammatory actions against dangerously high levels of IL-6. Based on these findings, our results suggest beneficial effects of long-term intake of fish oil in reducing the inflammation associated with chronic epilepsy. PMID:28649227
Kalemenev, S V; Zubareva, O E; Frolova, E V; Sizov, V V; Lavrentyeva, V V; Lukomskaya, N Ya; Kim, K Kh; Zaitsev, A V; Magazanik, L G
2015-01-01
Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy.
Eastman, Clifford L.; Fender, Jason S.; Temkin, Nancy R.; D’Ambrosio, Raimondo
2015-01-01
Conventionally developed antiseizure drugs fail to control epileptic seizures in about 30% of patients, and no treatment prevents epilepsy. New etiologically realistic, syndrome-specific epilepsy models are expected to identify better treatments by capturing currently unknown ictogenic and epileptogenic mechanisms that operate in the corresponding patient populations. Additionally, the use of electrocorticography permits better monitoring of epileptogenesis and the full spectrum of acquired seizures, including focal nonconvulsive seizures that are typically difficult to treat in humans. Thus, the combined use of etiologically realistic models and electrocorticography may improve our understanding of the genesis and progression of epilepsy, and facilitate discovery and translation of novel treatments. However, this approach is labor intensive and must be optimized. To this end, we used an etiologically realistic rat model of posttraumatic epilepsy, in which the initiating fluid percussion injury closely replicates contusive closed-head injury in humans, and has been adapted to maximize epileptogenesis and focal non-convulsive seizures. We obtained week-long 5-electrode electrocorticography 1 month post-injury, and used a Monte-Carlo-based non-parametric bootstrap strategy to test the impact of electrode montage design, duration-based seizure definitions, group size and duration of recordings on the assessment of posttraumatic epilepsy, and on statistical power to detect antiseizure and antiepileptogenic treatment effects. We found that use of seizure definition based on clinical criteria rather than event duration, and of recording montages closely sampling the activity of epileptic foci, maximize the power to detect treatment effects. Detection of treatment effects was marginally improved by prolonged recording, and 24 h recording epochs were sufficient to provide 80% power to detect clinically interesting seizure control or prevention of seizures with small groups
van Luijtelaar, Gilles; Lüttjohann, Annika; Makarov, Vladimir V; Maksimenko, Vladimir A; Koronovskii, Alexei A; Hramov, Alexander E
2016-02-15
Genetic rat models for childhood absence epilepsy have become instrumental in developing theories on the origin of absence epilepsy, the evaluation of new and experimental treatments, as well as in developing new methods for automatic seizure detection, prediction, and/or interference of seizures. Various methods for automated off and on-line analyses of ECoG in rodent models are reviewed, as well as data on how to interfere with the spike-wave discharges by different types of invasive and non-invasive electrical, magnetic, and optical brain stimulation. Also a new method for seizure prediction is proposed. Many selective and specific methods for off- and on-line spike-wave discharge detection seem excellent, with possibilities to overcome the issue of individual differences. Moreover, electrical deep brain stimulation is rather effective in interrupting ongoing spike-wave discharges with low stimulation intensity. A network based method is proposed for absence seizures prediction with a high sensitivity but a low selectivity. Solutions that prevent false alarms, integrated in a closed loop brain stimulation system open the ways for experimental seizure control. The presence of preictal cursor activity detected with state of the art time frequency and network analyses shows that spike-wave discharges are not caused by sudden and abrupt transitions but that there are detectable dynamic events. Their changes in time-space-frequency characteristics might yield new options for seizure prediction and seizure control. Copyright © 2015 Elsevier B.V. All rights reserved.
Common and Distinctive Patterns of Cognitive Dysfunction in Children With Benign Epilepsy Syndromes.
Cheng, Dazhi; Yan, Xiuxian; Gao, Zhijie; Xu, Keming; Zhou, Xinlin; Chen, Qian
2017-07-01
Childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes are the most common forms of benign epilepsy syndromes. Although cognitive dysfunctions occur in children with both childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, the similarity between their patterns of underlying cognitive impairments is not well understood. To describe these patterns, we examined multiple cognitive functions in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. In this study, 43 children with childhood absence epilepsy, 47 children with benign childhood epilepsy with centrotemporal spikes, and 64 control subjects were recruited; all received a standardized assessment (i.e., computerized test battery) assessing processing speed, spatial skills, calculation, language ability, intelligence, visual attention, and executive function. Groups were compared in these cognitive domains. Simple regression analysis was used to analyze the effects of epilepsy-related clinical variables on cognitive test scores. Compared with control subjects, children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes showed cognitive deficits in intelligence and executive function, but performed normally in language processing. Impairment in visual attention was specific to patients with childhood absence epilepsy, whereas impaired spatial ability was specific to the children with benign childhood epilepsy with centrotemporal spikes. Simple regression analysis showed syndrome-related clinical variables did not affect cognitive functions. This study provides evidence of both common and distinctive cognitive features underlying the relative cognitive difficulties in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. Our data suggest that clinicians should pay particular attention to the specific cognitive deficits in
Lakatos, Renáta Krisztina; Dobolyi, Árpád; Todorov, Mihail Ivilinov; Kékesi, Katalin A; Juhász, Gábor; Aleksza, Magdolna; Kovács, Zsolt
2016-06-01
The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system. Copyright © 2016 Elsevier Inc. All rights reserved.
Focal seizure symptoms in idiopathic generalized epilepsies.
Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl
2015-08-18
We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.
Phenotypic characterization of spontaneously mutated rats showing lethal dwarfism and epilepsy.
Suzuki, Hiroetsu; Takenaka, Motoo; Suzuki, Katsushi
2007-08-01
We have characterized the phenotype of spontaneously mutated rats, found during experimental inbreeding in a closed colony of Wistar Imamichi rats. Mutant rats showed severe dwarfism, short lifespan (early postnatal lethality), and high incidence of epileptic seizures. Mutant rats showed growth retardation after 3 d of age, and at 21 d their weight was about 56% that of normal rats. Most mutant rats died without reaching maturity, and 95% of the mutant rats had an ataxic gait. About 34% of the dwarf rats experienced epileptic seizures, most of which started as 'wild running' convulsions, progressing to generalized tonic-clonic convulsions. At age 28 d, the relative weight of the testes was significantly lower, and the relative weight of the brain was significantly higher, in mutant than in normal rats. Histologically, increased apoptotic germ cells, lack of spermatocytes, and immature Leydig cells were found in the mutant testes, and extracellular vacuoles of various sizes were present in the hippocampus and amygdala of the mutant brain. Mutant rats had significantly increased concentrations of plasma urea nitrogen, creatinine, and inorganic phosphate, as well as decreased concentrations of plasma growth hormone. Hereditary analysis showed that the defects were inherited as a single recessive trait. We have named the hypothetically mutated gene as lde (lethal dwarfism with epilepsy).
A brief history of typical absence seizures - Petit mal revisited.
Brigo, Francesco; Trinka, Eugen; Lattanzi, Simona; Bragazzi, Nicola Luigi; Nardone, Raffaele; Martini, Mariano
2018-03-01
In this article, we have traced back the history of typical absence seizures, from their initial clinical description to the more recent nosological position. The first description of absence seizures was made by Poupart in 1705 and Tissot in 1770. In 1824, Calmeil introduced the term "absences", and in 1838, Esquirol for the first time used the term petit mal. Reynolds instead used the term "epilepsia mitior" (milder epilepsy) and provided a comprehensive description of absence seizures (1861). In 1854, Delasiauve ranked absences as the seizure type with lower severity and introduced the concept of idiopathic epilepsy. Otto Binswanger (1899) discussed the role of cortex in the pathophysiology of "abortive seizures", whereas William Gowers (1901) emphasized the importance of a detailed clinical history to identify nonmotor seizures or very mild motor phenomena which otherwise may go unnoticed or considered not epileptic. At the beginning of the 20th Century, the term pyknolepsy was introduced, but initially was not universally considered as a type of epilepsy; it was definitely recognized as an epileptic entity only in 1945, based on electroencephalogram (EEG) recordings. Hans Berger, the inventor of the EEG, made also the first EEG recording of an atypical absence (his results were published only in 1933), whereas the characteristic EEG pattern was reported by neurophysiologists of the Harvard Medical School in 1935. The discovery of EEG made it also possible to differentiate absence seizures from so called "psychomotor" seizures occurring in temporal lobe epilepsy. Penfield and Jasper (1938) considered absences as expression of "centrencephalic epilepsy". Typical absences seizures are now classified by the International League Against Epilepsy among generalized nonmotor (absence) seizures. Copyright © 2018 Elsevier Inc. All rights reserved.
Attention Contributes to Arithmetic Deficits in New-Onset Childhood Absence Epilepsy.
Cheng, Dazhi; Yan, Xiuxian; Gao, Zhijie; Xu, Keming; Chen, Qian
2017-01-01
Neuropsychological studies indicate that new-onset childhood absence epilepsy (CAE) is associated with deficits in attention and executive functioning. However, the contribution of these deficits to impaired academic performance remains unclear. We aimed to examine whether attention and executive functioning deficits account for the academic difficulties prevalent in patients with new-onset CAE. We analyzed cognitive performance in several domains, including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention, and executive functioning, in 35 children with new-onset CAE and 33 control participants. Patients with new-onset CAE exhibited deficits in mathematics, general intelligence, attention, and executive functioning. Furthermore, attention deficits, as measured by a visual tracing task, accounted for impaired arithmetic performance in the new-onset CAE group. Therefore, attention deficits, rather than impaired general intelligence or executive functioning, may be responsible for arithmetic performance deficits in patients with new-onset CAE.
Protective Effect of Resveratrol on the Brain in a Rat Model of Epilepsy.
Li, Zhen; You, Zhuyan; Li, Min; Pang, Liang; Cheng, Juan; Wang, Liecheng
2017-06-01
Accumulating evidence has suggested resveratrol as a promising drug candidate for the treatment of epilepsy. To validate this, we tested the protective effect of resveratrol on a kainic acid (KA)-induced epilepsy model in rats and investigated the underlying mechanism. We found that acute resveratrol application partially inhibited evoked epileptiform discharges in the hippocampal CA1 region. During acute, silent and chronic phases of epilepsy, the expression of hippocampal kainate glutamate receptor (GluK2) and the GABA A receptor alpha1 subunit (GABA A R-alpha1) was up-regulated and down-regulated, respectively. Resveratrol reversed these effects and induced an antiepileptic effect. Furthermore, in the chronic phase, resveratrol treatment inhibited the KA-induced increased glutamate/GABA ratio in the hippocampus. The antiepileptic effects of resveratrol may be partially attributed to the reduction of glutamate-induced excitotoxicity and the enhancement in GABAergic inhibition.
[Cholinergic mechanisms in the pathogenesis of genetically-caused absence epilepsy].
Berdiev, R K; Chepurnov, S A; Chepurnova, N E; van Luijtelaar, E L
2003-01-01
Frontoparietal cortex and the thalamocortical circuit comprising reticular thalamic nucleus (RTN) and relay nuclei of the ventrolateral thalamus (VLT) are critical structures in the generation of spike-wave discharges (SWD) during absence seizures. The activity of these nuclei is under the control of the ascending cholinergic projections of nucleus basalis of Meynert. The aim of our study is to make an attempt to change the pattern of SWD in WAG/Rij rats by injecting of cholinotoxine AF64A to the area of RTN. Spontaneous SWD were registered in cortex of WAG/Rij rats with genetically determined absences. The spectral content of SWD was analyzed by means of the Fast Fourier Transformation (FFT) procedure. Unilateral injections of AF64A (1 nmol) to RTN led the decrease in duration and number of SWD comparing to the basal EEG recordings 2 days after the lesion. The FFT analysis showed the disappearance of 17-18 Hz spike on the side of the lesion compared with the intact side. The immunohistochemical study for acetylcholinetransferase (ChaT)-containing neurons showed the loss of ChaT-positive cells in the nucleus basalis area on the side of the lesion. The removal of cholinergic afferentation of RTN and cortex from nucleus basalis inhibits the SWD developing most likely due to the decrease of cortical excitability. Moreover, possibly cholinergic transmission is involved in the transforation of the synchronized phenomena (SWD) to another with close mechanism of generation.
Cain, Stuart M; Tyson, John R; Jones, Karen L; Snutch, Terrance P
2015-06-01
Burst-firing in distinct subsets of thalamic relay (TR) neurons is thought to be a key requirement for the propagation of absence seizures. However, in the well-regarded Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model as yet there has been no link described between burst-firing in TR neurons and spike-and-wave discharges (SWDs). GAERS ventrobasal (VB) neurons are a specific subset of TR neurons that do not normally display burst-firing during absence seizures in the GAERS model, and here, we assessed the underlying relationship of VB burst-firing with Ih and T-type calcium currents between GAERS and non-epileptic control (NEC) animals. In response to 200-ms hyperpolarizing current injections, adult epileptic but not pre-epileptic GAERS VB neurons displayed suppressed burst-firing compared to NEC. In response to longer duration 1,000-ms hyperpolarizing current injections, both pre-epileptic and epileptic GAERS VB neurons required significantly more hyperpolarizing current injection to burst-fire than those of NEC animals. The current density of the Hyperpolarization and Cyclic Nucleotide-activated (HCN) current (Ih) was found to be increased in GAERS VB neurons, and the blockade of Ih relieved the suppressed burst-firing in both pre-epileptic P15-P20 and adult animals. In support, levels of HCN-1 and HCN-3 isoform channel proteins were increased in GAERS VB thalamic tissue. T-type calcium channel whole-cell currents were found to be decreased in P7-P9 GAERS VB neurons, and also noted was a decrease in CaV3.1 mRNA and protein levels in adults. Z944, a potent T-type calcium channel blocker with anti-epileptic properties, completely abolished hyperpolarization-induced VB burst-firing in both NEC and GAERS VB neurons.
Hellier, J L; Patrylo, P R; Buckmaster, P S; Dudek, F E
1998-06-01
Human temporal lobe epilepsy is associated with complex partial seizures that can produce secondarily generalized seizures and motor convulsions. In some patients with temporal lobe epilepsy, the seizures and convulsions occur following a latent period after an initial injury and may progressively increase in frequency for much of the patient's life. Available animal models of temporal lobe epilepsy are produced by acute treatments that often have high mortality rates and/or are associated with a low proportion of animals developing spontaneous chronic motor seizures. In this study, rats were given multiple low-dose intraperitoneal (i.p.) injections of kainate in order to minimize the mortality rate usually associated with single high-dose injections. We tested the hypothesis that these kainate-treated rats consistently develop a chronic epileptic state (i.e. long-term occurrence of spontaneous, generalized seizures and motor convulsions) following a latent period after the initial treatment. Kainate (5 mg/kg per h, i.p.) was administered to rats every hour for several hours so that class III-V seizures were elicited for > or = 3 h, while control rats were treated similarly with saline. This treatment protocol had a relatively low mortality rate (15%). After acute treatment, rats were observed for the occurrence of motor seizures for 6-8 h/week. Nearly all of the kainate-treated rats (97%) had two or more spontaneous motor seizures months after treatment. With this observation protocol, the average latency for the first spontaneous motor seizure was 77+/-38 (+/-S.D.) days after treatment. Although variability was observed between rats, seizure frequency initially increased with time after treatment, and nearly all of the kainate-treated rats (91%) had spontaneous motor seizures until the time of euthanasia (i.e. 5-22 months after treatment). Therefore, multiple low-dose injections of kainate, which cause recurrent motor seizures for > or = 3 h, lead to the
Halliday, Amy J; Campbell, Toni E; Nelson, Timothy S; McLean, Karen J; Wallace, Gordon G; Cook, Mark J
2013-01-01
Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site. Copyright © 2012 Elsevier Ltd. All rights reserved.
Bercum, Florencia M; Rodgers, Krista M; Benison, Alex M; Smith, Zachariah Z; Taylor, Jeremy; Kornreich, Elise; Grabenstatter, Heidi L; Dudek, F Edward; Barth, Daniel S
2015-12-02
Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. Copyright © 2015 the authors 0270-6474/15/3515894-09$15.00/0.
Kadish, Navah Ester; Baumann, Matthias; Pietz, Joachim; Schubert-Bast, Susanne; Reuner, Gitta
2013-10-01
Our prospective study aimed at the validation of EpiTrack Junior, a neuropsychological screening tool for attention and executive functions in children with epilepsy. Twenty-two children with absence epilepsy aged 8-17 years underwent comprehensive neuropsychological evaluation including EpiTrack Junior and measures of intelligence, verbal and nonverbal memory, word fluency and visuoconstructive organization. Concurrent and discriminant validity of EpiTrack Junior subtests and total score as well as sensitivity and specificity of the total score were analyzed. EpiTrack Junior total score was impaired in 59% of participants. Concurrent validity was demonstrated in 4/6 subtests and for the total score. Discriminant validity was shown with respect to verbal and nonverbal long-term memory. Sensitivity was higher than specificity and highest for the "working memory index". EpiTrack Junior is recommended as a sensitive and time-efficient screening tool for attention and executive functions in children with epilepsy. Impaired results should be followed up with detailed evaluation including information from the parents and school as well as counseling where indicated. © 2013.
Suzuki, H; Katayama, K; Takenaka, M; Amakasu, K; Saito, K; Suzuki, K
2009-10-01
The lde/lde rat is characterized by dwarfism, postnatal lethality, male hypogonadism, a high incidence of epilepsy and many vacuoles in the hippocampus and amygdala. We used a candidate approach to identify the gene responsible for the lde phenotype and assessed the susceptibility of lde/lde rats for audiogenic seizures. Following backcross breeding of lethal dwarfism with epilepsy (LDE) to Brown Norway rats, the lde/lde rats with an altered genetic background showed all pleiotropic phenotypes. The lde locus was mapped to a 1.5-Mbp region on rat chromosome 19 that included the latter half of the Wwox gene. Sequencing of the full-length Wwox transcript identified a 13-bp deletion in exon 9 in lde/lde rats. This mutation causes a frame shift, resulting in aberrant amino acid sequences at the C-terminal. Western blotting showed that both the full-length products of the Wwox gene and its isoform were present in normal testes and hippocampi, whereas both products were undetectable in the testes and hippocampi of lde/lde rats. Sound stimulation induced epileptic seizures in 95% of lde/lde rats, with starting as wild running (WR), sometimes progressing to tonic-clonic convulsions. Electroencephalogram (EEG) analysis showed interictal spikes, fast waves during WR and burst of spikes during clonic phases. The Wwox protein is expressed in the central nervous system (CNS), indicating that abnormal neuronal excitability in lde/lde rats may be because of a lack of Wwox function. The lde/lde rat is not only useful for understanding the multiple functions of Wwox but is also a unique model for studying the physiological function of Wwox in CNS.
Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats
NASA Astrophysics Data System (ADS)
Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.
2015-03-01
In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.
Whole-brain MEG connectivity-based analyses reveals critical hubs in childhood absence epilepsy.
Youssofzadeh, Vahab; Agler, William; Tenney, Jeffrey R; Kadis, Darren S
2018-06-04
Absence seizures are thought to be linked to abnormal interplays between regions of a thalamocortical network. However, the complexity of this widespread network makes characterizing the functional interactions among various brain regions challenging. Using whole-brain functional connectivity and network analysis of magnetoencephalography (MEG) data, we explored pre-treatment brain hubs ("highly connected nodes") of patients aged 6 to 12 years with childhood absence epilepsy. We analyzed ictal MEG data of 74 seizures from 16 patients. We employed a time-domain beamformer technique to estimate MEG sources in broadband (1-40 Hz) where the greatest power changes between ictal and preictal periods were identified. A phase synchrony measure, phase locking value, and a graph theory metric, eigenvector centrality (EVC), were utilized to quantify voxel-level connectivity and network hubs of ictal > preictal periods, respectively. A volumetric atlas containing 116 regions of interests (ROIs) was utilized to summarize the network measures. ROIs with EVC (z-score) > 1.96 were reported as critical hubs. ROIs analysis revealed functional-anatomical hubs in a widespread network containing bilateral precuneus (right/left, z = 2.39, 2.18), left thalamus (z = 2.28), and three anterior cerebellar subunits of lobule "IV-V" (z = 3.9), vermis "IV-V" (z = 3.57), and lobule "III" (z = 2.03). Findings suggest that highly connected brain areas or hubs are present in focal cortical, subcortical, and cerebellar regions during absence seizures. Hubs in thalami, precuneus and cingulate cortex generally support a theory of rapidly engaging and bilaterally distributed networks of cortical and subcortical regions responsible for seizures generation, whereas hubs in anterior cerebellar regions may be linked to terminating motor automatisms frequently seen during typical absence seizures. Whole-brain network connectivity is a powerful analytic tool to reveal focal
Campbell, John N; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B
2014-01-01
Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later.
Alkawadri, Rafeed; So, Norman K.; Van Ness, Paul C.; Alexopoulos, Andreas V.
2016-01-01
present with electroclinical findings that are suggestive of temporal lobe epilepsy and can be considered as another example of pseudotemporal epilepsies. The electroclinical presentation and surgical outcome of lesional anterior cingulate epilepsy is possibly influenced by the underlying pathology. This study highlights the difficulty in localizing seizures arising from the cingulate gyrus in the absence of a magnetic resonance image lesion. PMID:23753910
Campbell, John N.; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B.
2014-01-01
Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later. PMID:25580467
Yi, Pei-Lu; Lu, Chin-Yu; Jou, Shuo-Bin; Chang, Fang-Chia
2015-07-07
The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high-frequency (100 Hz) electroacupuncture (EA) at Feng-Chi acupoints deteriorates both pilocarpine-induced focal epilepsy and sleep disruptions. This study investigated the effects of low-frequency (10 Hz) EA on epileptic activities and epilepsy-induced sleep disruptions. In rats, the Feng-Chi acupoint is located 3 mm away from the center of a line between the two ears. Rats received 30 min of 10 Hz EA stimuli per day before each day's dark period for three consecutive days. Our results indicated that administration of pilocarpine into the left CeA at the beginning of the dark period induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep during the consequent light period. Low-frequency (10 Hz) EA at Feng-Chi acupoints suppressed pilocarpine-induced epileptiform EEGs, and this effect was in turn blocked by naloxone (a broad-spectrum opioid receptor antagonist), but not by naloxonazine (a μ-receptor antagonist), naltrindole (a δ-receptor antagonist) and nor-binaltorphimine (a κ-receptor antagonist). Ten Hz EA enhanced NREM sleep during the dark period, and this enhancement was blocked by all of the opioid receptor antagonists. On the other hand, 10 Hz EA reversed pilocarpine-induced NREM suppression during the light period, and the EA's effect on the sleep disruption was only blocked by naloxonazine. These results indicate that low-frequency EA stimulation of Feng-Chi acupoints is beneficial in improving epilepsy and epilepsy-induced sleep disruptions, and that opioid receptors in the CeA mediate EA's therapeutic effects.
Treatment of pediatric epilepsy in Poland.
Dunin-Wąsowicz, Dorota; Mazurkiewicz-Bełdzińska, Maria; Steinborn, Barbara; Wheless, James; Jóźwiak, Sergiusz
2015-05-01
The many types of childhood epilepsies make the diagnosis and treatment difficult and the outcomes frequently poor. Furthermore, there are few clinical trials in pediatric epilepsy that provide useful results to guide daily practice. Therefore for pediatric neurologists expert opinion may be useful. To provide an overview of current practice in Poland and compare results with European and US clinical guidelines. Polish specialists in pediatric neurology were asked to participate in a survey about pediatric epilepsy. The focus of the questions was on the overall strategy and treatment options for different syndromic diagnoses. The survey was developed and performed according to a previous European survey (Wheless et al., 2007). Fifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen. Polish pediatric neurologists agreed on the majority of questions. Their views reflect the clinical utility and availability of treatment options in Poland. Results may provide direction for clinicians. Copyright © 2015. Published by Elsevier Ltd.
Proepileptic patterns in EEG of WAG/Rij rats
NASA Astrophysics Data System (ADS)
Grubov, Vadim V.; Sitnikova, Evgenia Yu.; Nedaivozov, Vladimir O.; Koronovskii, Alexey A.
2018-04-01
In this paper we study specific oscillatory patterns on EEG signals of WAG/Rij rats. These patterns are known as proepileptic because they occur in time period during the development of absence-epilepsy before fully-formed epileptic seizures. In the paper we analyze EEG signals of WAG/Rij rats with continuous wavelet transform and empirical mode decomposition in order to find particular features of epileptic spike-wave discharges and nonepileptic sleep spindles. Then we introduce proepileptic activity as patterns that combine features of epileptic and non-epileptic activity. We analyze proepileptic activity in order to specify its features and time-frequency structure.
Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin
Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J
2016-01-01
The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247
Li, Qinrui; Han, Ying; Du, Junbao; Jin, Hongfang; Zhang, Jing; Niu, Manman; Qin, Jiong
2018-05-01
Current studies have indicated that apoptotic and autophagic signaling pathways are triggered by epileptic seizures, but the precise roles of these processes in epilepsy-induced neuronal loss remain unclear. Identifying a concrete molecular mechanism may help researchers develop relevant epilepsy therapies that are more effective than existing treatments. Autophagy is a type of conserved degradation that contributes to cellular homeostasis. The involved signaling pathways allow us to observe alterations in autophagy and apoptosis during epileptic seizures over time. This study investigated the time-dependent changes in autophagy, apoptosis and neuronal morphology in developing brain of epilepsy model rats. At 48h after epileptic seizure onset, the number of neurons in neocortex decreased, and the number of apoptotic cells in neocortex increased. The ratio of microtubule-associated protein 1 light chain 3 (LC3) II to LC3 I and Beclin-1 protein levels increased from 12h to 48h after epileptic seizure onset. P62 protein and Bcl-2 protein levels decreased from 24h to 48h after epileptic seizure onset. The changes in the levels of these autophagy and apoptosis markers indicate that autophagy starts before apoptosis in rats with epilepsy, demonstrating a potential role of autophagy in epilepsy-induced neuronal loss in developing brain. Copyright © 2017. Published by Elsevier B.V.
Wu, Qiang; Yi, Xuewei
2018-06-01
Epilepsy is a common chronic brain disorder and is characterized by an enduring predisposition to generate seizures. The hippocampus is especially vulnerable to seizure-induced damage. In this study, we explore the ability of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) to influence the autophagy and apoptosis of hippocampal neurons in epilepsy and the underlying mechanism involving the PI3K/Akt signaling pathway. Seventy-two Sprague-Dawley rats were assigned to normal, sham, Ep, Ep + si-NC, Ep + si-MALAT1, and Ep + si-MALAT1 + LY groups. Fluorescence in situ hybridization kit was employed to determine the MALAT1 in the brain tissues. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the expression of MALAT1, mRNAs, and proteins. The autophagy of hippocampal neurons was evaluated under a transmission electron microscope and their apoptosis was evaluated using TUNEL staining. We found that MALAT1 and c-Met were enriched while microRNA-101 (miR-101) decreased in rats with epilepsy. The demonstration showed that MALAT1 binds to miR-101, thus regulating c-Met. In rats with epilepsy, MALAT1 depletion mediated by anti-MALAT1 siRNA resulted in activation of PI3K/Akt signaling pathway and loss of hippocampal neurons. LY294002, an inhibitor of PI3K/Akt signaling pathway, could reverse the events caused by MALAT1 knockdown. Taken together, these findings indicate that down-regulation of MALAT1 activates the PI3K/Akt signaling pathway to protect hippocampal neurons against autophagy and apoptosis in rats with epilepsy.
2014-09-01
delivery persistently reduces seizure severity in a rat model of temporal lobe epilepsy ," Session number: 314, Session title: Non-pharmacological...delivery persistently reduces seizure severity in a rat model of temporal lobe epilepsy Location: WCC Hall A-C Presentation time: Monday, Nov 17, 2014...therapeutic potential administered prior to last-resort neurosurgical resections in pharmacoresistant cases of temporal lobe epilepsy . Disclosures: G. Natarajan
Löscher, Wolfgang; Ferland, Russell J; Ferraro, Thomas N
2017-08-01
It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals' performance in behavioral tests that often accompany acute and chronic seizure testing. Copyright © 2017 Elsevier Inc. All rights reserved.
Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy
NASA Astrophysics Data System (ADS)
Ren, Min-Qin; Ong, Wei-Yi; Makjanic, Jagoda; Watt, Frank
1999-10-01
Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.
Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.
Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H
2016-12-01
Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.
Li, Ruohan; Ma, Limin; Huang, Hao; Ou, Shu; Yuan, Jinxian; Xu, Tao; Yu, Xinyuan; Liu, Xi; Yang, Juan; Chen, Yangmei; Peng, Xi
2017-02-01
The mechanisms that underlie the pathogenesis of epilepsy are still unclear. Recent studies have indicated that inflammatory processes occurring in the brain are involved in a common and crucial mechanism in epileptogenesis. C-X-C motif chemokine ligand 13 (CXCL13) and its only receptor, C-X-C motif chemokine receptor 5 (CXCR5), are highly expressed in the central nervous system (CNS) and participate in inflammatory responses. The present study aimed to assess the expression of CXCL13 and CXCR5 in the brain tissues of both patients with intractable epilepsy (IE) and a rat model (lithium-pilocarpine) of temporal lobe epilepsy (TLE) to identify possible roles of the CXCL13-CXCR5 signaling pathway in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemical, double-labeled immunofluorescence and Western blot analyses were performed in this study. CXCL13 and CXCR5 mRNA expression and protein levels were found to be significantly up-regulated in the TLE patients and TLE rats. Further, CXCL13 and CXCR5 protein levels were altered during the different epileptic phases after onset of status epilepticus (SE) in the pilocarpine model rats, including the acute phase (6, 24, and 72 h), latent phase (7 and 14 days) and chronic phase (30 and 60 days groups). Moreover, double-labeled immunofluorescence analysis revealed that CXCL13 was mainly expressed in the cytomembranes and cytoplasm of neurons and astrocytes, while CXCR5 was mainly expressed in the cytomembranes and cytoplasm of neurons. Thus, the CXCL13-CXCR5 signaling pathway may play a possible pathogenic role in IE. CXCL13 and CXCR5 may represent potential biomarkers of brain inflammation in epileptic patients.
Mármol, F; Sánchez, J; Torres, M N; Chamizo, V D
2017-11-01
The effects of early environmental enrichment (EE) when solving a simple spatial task in adult male rats were assessed. After weaning, rats were housed in pairs in enriched or standard cages (EE and control groups) for two and a half months. Then the rats were trained in a triangular-shaped pool to find a hidden platform whose location was defined in terms of two sources of information, a landmark outside the pool and a particular corner of the pool. As expected, enriched rats reached the platform faster than control animals. Enriched rats also performed better on a subsequent test trial without the platform with the geometry cue individually presented (in the absence of the landmark). Most importantly, the beneficial effects of the present protocol were obtained in the absence of wheel running. Additionally, the antioxidative effects in the hippocampus produced by the previous protocol are also shown. Copyright © 2017 Elsevier B.V. All rights reserved.
Recent advances in drug therapy for epilepsy.
Bruni, J.
1979-01-01
Recent advances in drug therapy for epilepsy have contributed to the reduction in the proportion of persons whose epilepsy is uncontrolled. New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses. Carbamazepine has recently been introduced for the treatment of generalized tonic-clonic and partial seizures. Clonazepam has been found of particular benefit in the treatment of absence and myoclonic seizures. Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures. Monitoring of the plasma concentration of antiepileptic drugs has added greatly to the achievement of optimal drug therapy and the prevention of toxic effects. PMID:371777
High-Frequency Oscillations and Seizure Generation in Neocortical Epilepsy
ERIC Educational Resources Information Center
Worrell, Greg A.; Parish, Landi; Cranstoun, Stephen D.; Jonas, Rachel; Baltuch, Gordon; Litt, Brian
2004-01-01
Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60--100 Hz) epileptiform oscillations…
Control of Absence Seizures by the Thalamic Feed-Forward Inhibition
Chen, Mingming; Guo, Daqing; Xia, Yang; Yao, Dezhong
2017-01-01
As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed to be caused by pathological interactions within the corticothalamic (CT) system. Using a biophysical mean-field model of the CT system, we demonstrate here that the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx, may participate in controlling absence seizures. In particular, we show that increasing the excitatory Ctx-TRN coupling strength can significantly suppress typical electrical activities during absence seizures. Further, investigation demonstrates that the GABAA- and GABAB-mediated inhibitions in the TRN-SRN pathway perform combination roles in the regulation of absence seizures. Overall, these results may provide an insightful mechanistic understanding of how the thalamic FFI serves as an intrinsic regulator contributing to the control of absence seizures. PMID:28491031
Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy
Mendonça, Fabricio N.; Santos, Luiz E. C.; Rodrigues, Antônio M.; Gomes da Silva, Sérgio; Arida, Ricardo M.; da Silveira, Gilcélio A.; Scorza, Fulvio A.; Almeida, Antônio-Carlos G.
2017-01-01
Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group. Notably, a larger number of newborn granule cells exhibiting morphological characteristics indicative of correct targeting into the hippocampal circuitry and the absence of basal dendrite projections was also observed in the epileptic animals subjected to physical exercise compared to the epileptic animals. The results described here could represent a positive interference of the physical exercise on the neurogenesis process in subjects with chronic epilepsy. The results may also help to reinterpret the benefits of the physical exercise in alleviating symptoms of depression and cognitive dysfunction. PMID:28298884
Kendirli, M Tansel; Rose, Dominique T; Bertram, Edward H
2014-12-01
Penetrating brain injury (PBI) has the highest risk for inducing posttraumatic epilepsy, and those PBIs with retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-electroencephalography (EEG). A separate set of animals was examined for possible acute seizures in the week following the injury. Twenty-two of the 23 animals with copper wire developed chronic epilepsy, compared to three of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute postinjury seizures. Lesion size may contribute to epilepsy development in lesion-only animals. Copper may be an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy
Rudolf, Gabrielle; Lesca, Gaetan; Mehrjouy, Mana M; Labalme, Audrey; Salmi, Manal; Bache, Iben; Bruneau, Nadine; Pendziwiat, Manuela; Fluss, Joel; de Bellescize, Julitta; Scholly, Julia; Møller, Rikke S; Craiu, Dana; Tommerup, Niels; Valenti-Hirsch, Maria Paola; Schluth-Bolard, Caroline; Sloan-Béna, Frédérique; Helbig, Katherine L; Weckhuysen, Sarah; Edery, Patrick; Coulbaut, Safia; Abbas, Mohamed; Scheffer, Ingrid E; Tang, Sha; Myers, Candace T; Stamberger, Hannah; Carvill, Gemma L; Shinde, Deepali N; Mefford, Heather C; Neagu, Elena; Huether, Robert; Lu, Hsiao-Mei; Dica, Alice; Cohen, Julie S; Iliescu, Catrinel; Pomeran, Cristina; Rubenstein, James; Helbig, Ingo; Sanlaville, Damien; Hirsch, Edouard; Szepetowski, Pierre
2016-01-01
Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5–10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures. PMID:27352968
Drion, Cato M; Borm, Lars E; Kooijman, Lieneke; Aronica, Eleonora; Wadman, Wytse J; Hartog, Aloysius F; van Vliet, Erwin A; Gorter, Jan A
2016-05-01
Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the electrogenic post-status epilepticus (SE) rat model. Effects of mTOR inhibitor rapamycin were tested using the following three treatment protocols: (1) "stop-treatment"-post-SE treatment (6 mg/kg/day) was discontinued after 3 weeks; rats were monitored for 5 more weeks thereafter, (2) "pretreatment"-rapamycin (3 mg/kg/day) was applied during 3 days preceding SE; and (3) "chronic phase-treatment"-5 days rapamycin treatment (3 mg/kg/day) in the chronic phase. We also tested curcumin, an alternative mTOR inhibitor with antiinflammatory and antioxidant effects, using chronic phase treatment. Seizures were continuously monitored using video-electroencephalography (EEG) recordings; mossy fiber sprouting, cell death, and inflammation were studied using immunohistochemistry. Blood was withdrawn regularly to assess rapamycin and curcumin levels with high performance liquid chromatography (HPLC). Stop-treatment led to a strong reduction of seizures during the 3-week treatment and a gradual reappearance of seizures during the following 5 weeks. Three days pretreatment did not prevent seizure development, whereas 5-day rapamycin treatment in the chronic phase reduced seizure frequency. Washout of rapamycin was slow and associated with a gradual reappearance of seizures. Rapamycin treatment (both 3 and 6 mg/kg) led to body growth reduction. Curcumin treatment did not reduce seizure frequency or lead to a decrease in body weight. The present study indicates that rapamycin cannot prevent epilepsy in the electrical stimulation post-SE rat model but has seizure-suppressing properties as long as rapamycin blood levels are sufficiently high. Oral curcumin treatment had no effect on chronic
Absence of gender effect on amygdala volume in temporal lobe epilepsy.
Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora
2010-11-01
Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. Copyright © 2010 Elsevier Inc. All rights reserved.
Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy.
Reddy, Doodipala Samba
2016-01-01
Catamenial epilepsy is a type of refractory epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of catamenial epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual catamenial epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of catamenial epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of catamenial epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for catamenial epilepsy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fisher, R.S.; Frost, J.J.
1991-04-01
As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18(F)FDG inmore » some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18(F)FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.95 references.« less
Kendirli, M. Tansel; Rose, Dominique T.; Bertram, Edward H.
2014-01-01
Objective Penetrating brain injury (PBI) has the highest risk for inducing post-traumatic epilepsy and retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Methods Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-EEG. A separate set of animals was examined for possible acute seizures in the week following the injury. Results 22 of the 23 animals with copper wire developed chronic epilepsy compared to 3 of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Conclusions Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute post-injury seizures. Lesion size may contribute to epilepsy development in lesion only animals. Copper maybe an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. PMID:25470332
Huang, Hao; Li, Ruohan; Yuan, Jinxian; Zhou, Xin; Liu, Xi; Ou, Shu; Xu, Tao; Chen, Yangmei
2016-05-15
EphB family receptor tyrosine kinases, in cooperation with cell surface-bound ephrinB ligands, play a critical role in maintenance of dendritic spine morphogenesis, axons guidance, synaptogenesis, synaptic reorganization and plasticity in the central nervous system (CNS). However, the expression pattern of ephrinB/EphB in intractable temporal lobe epilepsy (TLE) and the underlying molecular mechanisms during epileptogenesis remain poorly understood. Here we investigated the expression pattern and cellular distribution of ephrinB/EphB in intractable TLE patients and lithium chloride-pilocarpine induced TLE rats using real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, double-labeled immunofluorescence and Western blot analysis. Compared to control groups, ephrinB3 and EphB3 mRNA expression were significantly up-regulated in intractable TLE patients and TLE rats, while the mRNA expression trend of ephrinB1/2 and EphB1/2/4/6 in intractable TLE patients and TLE rats were inconsistent. Western blot analysis and semi-quantitative immunohistochemistry confirmed that ephrinB3 and EphB3 protein level were up-regulated in intractable TLE patients and TLE rats. At the same time, double-labeled immunofluorescence indicate that ephrinB3 was expressed mainly in the cytoplasm and protrusions of glia and neurons, while EphB3 was expressed mainly in the cytoplasm of neurons. Taken together, up-regulated expression of ephrinB3/EphB3 in intractable TLE patients and experimental TLE rats suggested that ephrinB3/EphB3 might be involved in the pathogenesis of TLE. Copyright © 2016 Elsevier B.V. All rights reserved.
Ren, L; Zhu, R; Li, X
2016-02-22
Epilepsy is one of the most frequent neurological disorders. Recently, the regulation of microRNAs was found to be associated with epilepsy, but the molecular mechanism by which microRNA influences epilepsy process remains to be unveiled and the development of microRNA-based therapy requires more intensive research. In this study, five microRNAs with potential relevance to epilepsy were initially chosen: miR-132, miR-146a, miR-181a, miR-34a, and miR-124. Twenty-five children who were patients with epilepsy were selected as subjects to obtain tissue samples for the study. The miRNA-181a, which represented the most increased fold-changes in clinical samples, were then selected for further function study in mouse model. The temporal lobe epilepsy (TLE) model, along with lithium-pilocarpine-induced status epilepticus (SE), was established in Sprague-Dawley rats. The antagomir of miR-181a was used to determine the role of miR-181a in cell apoptosis. Analyses were conducted to determine the expression levels of miR-181a, neuronal apoptosis in post-SE, and activated caspase-3. We found evidence of significant time dependent up-regulation of miR-181a amongst post-SE rats and TLE on 24 h (4.47 ± 0.35), 7 days (4.85 ± 0.53), and 2 weeks (5.66 ± 0.64). Experiments with the miR-181a antagomir showed that this particular miRNA led to the inhibition of the protein expression of caspase-3, and was up-regulated in the course of seizure-induced neuronal apoptosis. This study provided evidence that targeting miR-181a leads to a neuroprotective response and is linked to an increase in the activation of the caspase-3 protein. These findings suggest that miR-181a may serve as a promising therapeutic target for epilepsy.
CHD2 variants are a risk factor for photosensitivity in epilepsy
Myers, Candace T.; Leu, Costin; de Kovel, Carolien G. F.; Afrikanova, Tatiana; Cordero-Maldonado, Maria Lorena; Martins, Teresa G.; Jacmin, Maxime; Drury, Suzanne; Krishna Chinthapalli, V.; Muhle, Hiltrud; Pendziwiat, Manuela; Sander, Thomas; Ruppert, Ann-Kathrin; Møller, Rikke S.; Thiele, Holger; Krause, Roland; Schubert, Julian; Lehesjoki, Anna-Elina; Nürnberg, Peter; Lerche, Holger; Palotie, Aarno; Coppola, Antonietta; Striano, Salvatore; Gaudio, Luigi Del; Boustred, Christopher; Schneider, Amy L.; Lench, Nicholas; Jocic-Jakubi, Bosanka; Covanis, Athanasios; Capovilla, Giuseppe; Veggiotti, Pierangelo; Piccioli, Marta; Parisi, Pasquale; Cantonetti, Laura; Sadleir, Lynette G.; Mullen, Saul A.; Berkovic, Samuel F.; Stephani, Ulrich; Helbig, Ingo; Crawford, Alexander D.; Esguerra, Camila V.; Kasteleijn-Nolst Trenité, Dorothee G. A.
2015-01-01
Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2·17 × 10−5). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3·50 × 10−4). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research
Control of epileptic seizures in WAG/Rij rats by means of brain-computer interface
NASA Astrophysics Data System (ADS)
Makarov, Vladimir V.; Maksimenko, Vladimir A.; van Luijtelaar, Gilles; Lüttjohann, Annika; Hramov, Alexander E.
2018-02-01
The main issue of epileptology is the elimination of epileptic events. This can be achieved by a system that predicts the emergence of seizures in conjunction with a system that interferes with the process that leads to the onset of seizure. The prediction of seizures remains, for the present, unresolved in the absence epilepsy, due to the sudden onset of seizures. We developed an algorithm for predicting seizures in real time, evaluated it and implemented it into an online closed-loop brain stimulation system designed to prevent typical for the absence of epilepsy of spike waves (SWD) in the genetic rat model. The algorithm correctly predicts more than 85% of the seizures and the rest were successfully detected. Unlike the old beliefs that SWDs are unpredictable, current results show that they can be predicted and that the development of systems for predicting and preventing closed-loop capture is a feasible step on the way to intervention to achieve control and freedom from epileptic seizures.
Epilepsy, Cognition, and Behavior: The clinical picture
Berg, Anne T.
2010-01-01
Although epilepsy is defined by the occurrence of spontaneous epileptic seizures, a large body of evidence indicates that epilepsy is linked to a spectrum behavioral, psychiatric, and cognitive disorders as well as to sudden death. Explanations for these associations include: (1) The effects of structural lesions which may impair the functions subserved by the regions of the brain involved in the lesion. (2) The effects of seizure activity which may begin well before a clinical seizure occurs and may persist long after it is over raising questions about what truly constitutes “interictal.” In addition, encephalopathic effects of epilepsy in infancy during critical periods in development may be particularly severe and potentially irreversible. (3) Shared mechanisms underlying seizures as well as these other disorders in the absence of structural lesions or separate diseases of the CNS. Epidemiological and clinical studies demonstrate the elevated risk of cognitive, psychiatric, and behavioral disorders not just during but also prior to the onset of epilepsy (seizures) itself. These may outlast the active phase of epilepsy as well. The mounting evidence argues strongly for the recognition of epilepsy as part of a spectrum of disorders and against the notion that even uncomplicated epilepsy can a priori be considered benign. PMID:21214534
Das, Jharana; Singh, Rameshwar; Sharma, Deepak
2017-05-01
Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na + ,K + -ATPase activity) in both the cortex and the hippocampus. Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na + ,K + -ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.
Kanner, Andres M; Ashman, Eric; Gloss, David; Harden, Cynthia; Bourgeois, Blaise; Bautista, Jocelyn F; Abou-Khalil, Bassel; Burakgazi-Dalkilic, Evren; Llanas Park, Esmeralda; Stern, John; Hirtz, Deborah; Nespeca, Mark; Gidal, Barry; Faught, Edward; French, Jacqueline
2018-06-13
To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs). The 2004 AAN criteria were used to systematically review literature (January 2003-November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect-related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval. © 2018 American Academy of Neurology.
Validation of a Preclinical Drug Screening Platform for Pharmacoresistant Epilepsy.
Barker-Haliski, Melissa L; Johnson, Kristina; Billingsley, Peggy; Huff, Jennifer; Handy, Laura J; Khaleel, Rizvana; Lu, Zhenmei; Mau, Matthew J; Pruess, Timothy H; Rueda, Carlos; Saunders, Gerald; Underwood, Tristan K; Vanegas, Fabiola; Smith, Misty D; West, Peter J; Wilcox, Karen S
2017-07-01
The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents. It is clear that this traditional screening approach has greatly expanded the number of marketed drugs available to manage the symptomatic seizures associated with epilepsy. In spite of the numerous antiseizure drugs (ASDs) on the market today, the fact remains that nearly 30% of patients are resistant to these currently available medications. To address this unmet medical need, the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) revised its approach to the early evaluation of investigational agents for the treatment of epilepsy in 2015 to include a focus on preclinical approaches to model pharmacoresistant seizures. This present report highlights the in vivo and in vitro findings associated with the initial pharmacological validation of this testing approach using a number of mechanistically diverse, commercially available antiseizure drugs, as well as several probe compounds that are of potential mechanistic interest to the clinical management of epilepsy.
Høie, B; Mykletun, A; Sommerfelt, K; Bjørnaes, H; Skeidsvoll, H; Waaler, P E
2005-06-01
To study the relationship between seizure-related factors, non-verbal intelligence, and socio-economic status (SES) in a population-based sample of children with epilepsy. The latest ILAE International classifications of epileptic seizures and syndromes were used to classify seizure types and epileptic syndromes in all 6-12 year old children (N=198) with epilepsy in Hordaland County, Norway. The children had neuropediatric and EEG examinations. Of the 198 patients, demographic characteristics were collected on 183 who participated in psychological studies including Raven matrices. 126 healthy controls underwent the same testing. Severe non-verbal problems (SNVP) were defined as a Raven score at or <10th percentile. Children with epilepsy were highly over-represented in the lowest Raven percentile group, whereas controls were highly over-represented in the higher percentile groups. SNVP were present in 43% of children with epilepsy and 3% of controls. These problems were especially common in children with remote symptomatic epilepsy aetiology, undetermined epilepsy syndromes, myoclonic seizures, early seizure debut, high seizure frequency and in children with polytherapy. Seizure-related characteristics that were not usually associated with SNVP were idiopathic epilepsies, localization related (LR) cryptogenic epilepsies, absence and simple partial seizures, and a late debut of epilepsy. Adjusting for socio-economic status factors did not significantly change results. In childhood epilepsy various seizure-related factors, but not SES factors, were associated with the presence or absence of SNVP. Such deficits may be especially common in children with remote symptomatic epilepsy aetiology and in complex and therapy resistant epilepsies. Low frequencies of SNVP may be found in children with idiopathic and LR cryptogenic epilepsy syndromes, simple partial or absence seizures and a late epilepsy debut. Our study contributes to an overall picture of cognitive function
Prevalence and risk factors of seizure clusters in adult patients with epilepsy.
Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Wong, Rebecca A; Jiang, Alfred; Kato, Kenneth; Buchsbaum, Richard; Detyniecki, Kamil
2017-07-01
In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. We reviewed medical records of 4116 adult (≥16years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P<0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P<0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also
Altered mitochondrial acetylation profiles in a kainic acid model of temporal lobe epilepsy.
Gano, Lindsey B; Liang, Li-Ping; Ryan, Kristen; Michel, Cole R; Gomez, Joe; Vassilopoulos, Athanassios; Reisdorph, Nichole; Fritz, Kristofer S; Patel, Manisha
2018-08-01
Impaired bioenergetics and oxidative damage in the mitochondria are implicated in the etiology of temporal lobe epilepsy, and hyperacetylation of mitochondrial proteins has recently emerged as a critical negative regulator of mitochondrial functions. However, the roles of mitochondrial acetylation and activity of the primary mitochondrial deacetylase, SIRT3, have not been explored in acquired epilepsy. We investigated changes in mitochondrial acetylation and SIRT3 activity in the development of chronic epilepsy in the kainic acid rat model of TLE. Hippocampal measurements were made at 48 h, 1 week and 12 weeks corresponding to the acute, latent and chronic stages of epileptogenesis. Assessment of hippocampal bioenergetics demonstrated a ≥ 27% decrease in the ATP/ADP ratio at all phases of epileptogenesis (p < 0.05), whereas cellular NAD+ levels were decreased by ≥ 41% in the acute and latent time points (p < 0.05), but not in chronically epileptic rats. In spontaneously epileptic rats, we found decreased protein expression of SIRT3 and a 60% increase in global mitochondrial acetylation, as well as enhanced acetylation of the known SIRT3 substrates MnSOD, Ndufa9 of Complex I and IDH2 (all p < 0.05), suggesting SIRT3 dysfunction in chronic epilepsy. Mass spectrometry-based acetylomics investigation of hippocampal mitochondria demonstrated a 79% increase in unique acetylated proteins from rats in the chronic phase vs. controls. Pathway analysis identified numerous mitochondrial bioenergetic pathways affected by mitochondrial acetylation. These results suggest SIRT3 dysfunction and aberrant protein acetylation may contribute to mitochondrial dysfunction in chronic epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.
A Critical Evaluation of the Gamma-Hydroxybutyrate (GHB) Model of Absence Seizures
Venzi, Marcello; Di Giovanni, Giuseppe; Crunelli, Vincenzo
2015-01-01
Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the γ-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs. PMID:25403866
Aging models of acute seizures and epilepsy.
Kelly, Kevin M
2010-01-01
Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.
Han, Chun-Lei; Ge, Ming; Liu, Yun-Peng; Zhao, Xue-Min; Wang, Kai-Liang; Chen, Ning; Hu, Wei; Zhang, Jian-Guo; Li, Liang; Meng, Fan-Gang
2018-05-23
Temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy, characterized by hippocampal neuron damage and hippocampal sclerosis. Long noncoding RNAs (lncRNAs) have been increasingly recognized as posttranscriptional regulators. However, their expression levels and functions in TLE remain largely unknown. In the present study, TLE rat model is used to explore the expression profiles of lncRNAs in the hippocampus of epileptic rats using microarray analysis. Our results demonstrate that H19 is the most pronouncedly differentiated lncRNA, significantly upregulated in the latent period of TLE. Moreover, the in vivo studies using gain- and loss-of-function approaches reveal that the overexpression of H19 aggravates SE-induced neuron apoptosis in the hippocampus, while inhibition of H19 protects the rats from SE-induced cellular injury. Finally, we show that H19 might function as a competing endogenous RNA to sponge microRNA let-7b in the regulation of cellular apoptosis. Overall, our study reveals a novel lncRNA H19-mediated mechanism in seizure-induced neural damage and provides a new target in developing lncRNA-based strategies to reduce seizure-induced brain injury.
Ghazizadeh, Vahid; Nazıroğlu, Mustafa
2014-09-01
Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.
Autistic traits in epilepsy models: Why, when and how?
Velíšková, Jana; Silverman, Jill L; Benson, Melissa; Lenck-Santini, Pierre-Pascal
2018-05-18
Autism spectrum disorder (ASD) is a common comorbidity of epilepsy and seizures and/or epileptiform activity are observed in a significant proportion of ASD patients. Current research also implies that autistic traits can be observed to a various degree in mice and rats with seizures. This suggests that there are shared mechanisms in both ASD and epilepsy syndromes. Here, we first review the standard, validated methods used to assess autistic traits in animal models as well as their limitations with regards to epilepsy models. We then discuss two of the potential pathological processes that could be shared between ASD and epilepsy. We first focus on functional implications of neuroinflammation including changes to excitable networks mediated by inflammatory regulators. Finally we examine mechanisms at the cellular and network level involved in neuronal excitability, timing and network coordination that may directly lead to behavioral disturbances present in both epilepsy and ASD. This mini-review summarizes the work first presented at an Investigators Workshop at the 2016 American Epilepsy Society meeting. Copyright © 2018. Published by Elsevier B.V.
Epilepsy and Autism: Is there a special relationship?
Berg, Anne T.; Plioplys, Sigita
2012-01-01
Increasingly, there has been an interest in the association between epilepsy and autism. The high frequency of autism in some of the early-onset developmental encephalopathic epilepsies is frequently cited as evidence of the relationship between autism and epilepsy. While these specific forms of epilepsy carry a higher than expected risk of autism, most if not all of the association may be due to intellectual disability (ID). The high prevalence of interictal EEG discharges in children with autism is also cited as further evidence although errors in the diagnosis of epilepsy seem to account for at least part of those findings. The prevalence of ID is substantially elevated in children with either epilepsy or autism. In the absence of ID, there is little evidence of a substantial, if any, increased risk of autism in children with epilepsy. Further, although the reported prevalence of autism has increased over the last several years, much of this increase may be attributable to changes in diagnostic practices, conceptualization of autism in the presence of ID, and laws requiring provision of services for children with autism. In the context of these temporal trends, any further efforts to tease apart the relationships between epilepsy, ID, and autism will have to address head-on the accuracy of diagnosis of all three conditions before we can determine whether there is indeed a special relationship between autism and epilepsy. PMID:22381386
[Association between autism spectrum disorder and epilepsy in children].
Mei, Song-Li; Zhang, Zhao; Liu, Xin; Gao, Ting-Ting; Peng, Xin-Xian
2017-05-01
To examine the association between autism spectrum disorder (ASD) and epilepsy in children. A total of 190 children with ASD were enrolled. A self-designed questionnaire, Childhood Autism Rating Scale, and Autism Behavior Checklist were used to determine the association between ASD and epilepsy. Among the 190 children with ASD, 20 (10.5%) had epileptic seizures and 12 (6.3%) were diagnosed with epilepsy. The rates of abnormal physical development and hearing disorders before the age of one year were significantly higher in ASD children with epileptic seizures than in those without epileptic seizures (P<0.05). The ASD children diagnosed with epilepsy and those receiving epilepsy treatment had a significantly increased rate of abnormal physical development before the age of one year (P<0.05). The ASD children with epileptic seizures had poorer sensory responses and behavioral competencies than those without epileptic seizures (P<0.05). Epilepsy treatment have a positive effect on behavioral competencies in ASD children (P<0.05). There is a significant association between ASD and epilepsy in children. The possibility of the comorbidity between ASD and epilepsy may be assessed according to the status of growth and development before the age of one year, sensory responses and behavioral competencies, and the presence or absence of epileptic seizures.
The mean age of petit mal epilepsy.
Syeda, Afsarunnesa; Karim, Md Rezaul
2016-01-01
Petit mal epilepsy or absence seizures involve brief, sudden lapses of consciousness and most often occurs in people under age of 20 years. This study was done to find out the most likely significant age affected by petit mal epilepsy and whether they had higher rate of behavioral, educational, and social problems. We run tests on total 32 patients (male 16 and female 16) from newborns to 20 years of age. The most affected ages were from 4 to 9 years and both genders were equally affected. They have higher rate of behavioral, educational, and social problems, and most likely recovering ages from the disease were from 15 to 20 years. These findings could contribute in diagnosis and treatment of Petit Mal Epilepsy, as it often misinterpreted as daydreaming or inattention.
Occurrence and Recurrence of Attempted Suicide Among People With Epilepsy.
Hesdorffer, Dale C; Ishihara, Lianna; Webb, David J; Mynepalli, Lakshmi; Galwey, Nicholas W; Hauser, W Allen
2016-01-01
increased 1.8-fold (95% CI, 1.3- to 2.5-fold) for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed. Exclusion of antiepileptic drugs prescribed before the index date did not meaningfully alter the findings, nor did separate analyses of patients with and patients without diagnosed psychiatric disorders. Suicide attempts and recurrent suicide attempts are associated with epilepsy even before epilepsy manifests, suggesting a common underlying biology. Our findings indicate that both incident and recurrent suicide attempts are associated with incident epilepsy in the absence of antiepileptic drugs and in the absence of diagnosed psychiatric disorders, further strengthening the evidence for a common underlying etiology with an as-yet-unknown mechanism.
Dysgraphia as a Mild Expression of Dystonia in Children with Absence Epilepsy
Guerrini, Renzo; Melani, Federico; Brancati, Claudia; Ferrari, Anna Rita; Brovedani, Paola; Biggeri, Annibale; Grisotto, Laura; Pellacani, Simona
2015-01-01
Background Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia. Objectives Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer’s cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia. Methods We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.7) and average intelligence and compared them with 89 age-, gender- and class-matched healthy children (mean age 10.57) using tests for handwriting fluency and quality, based on which we divided patients and controls into four subgroups: AE/dysgraphia, AE without dysgraphia, controls with dysgraphia and healthy controls. We compared the blink reflex recovery cycle in children belonging to all four subgroups. Results We identified dysgraphia in 17/82 children with AE and in 7/89 controls (20.7 vs 7.8%; P = 0.016) with the former having a 3.4-times higher risk of dysgraphia regardless of age and gender (odd ratio: 3.49; 95% CI 1.2, 8.8%). The AE/dysgraphia subgroup performed worse than controls with dysgraphia in one test of handwriting fluency (P = 0.037) and in most trials testing handwriting quality (P< 0.02). In children with AE/dysgraphia the blink reflex showed no suppression at short interstimulus intervals, with a difference for each value emerging when comparing the study group with the three remaining subgroups (P<0.001). Conclusions In children with AE, dysgraphia is highly prevalent and has a homogeneous, distinctive pathophysiological substrate consistent with idiopathic dystonia. PMID:26132164
Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad
2016-01-01
Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress.
Barker-Haliski, Melissa L; Löscher, Wolfgang; White, H Steve; Galanopoulou, Aristea S
2017-07-01
Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis-induced epilepsy. Rat models of infantile spasms were generated in rat pups after right intracerebral injections of proinflammatory compounds (lipopolysaccharides with or without doxorubicin, or cytokines) and were longitudinally monitored for epileptic spasms and neurodevelopmental and cognitive deficits. Anti-inflammatory treatments were tested after the onset of spasms. The TMEV mouse model was induced with intracerebral administration of TMEV and prospective monitoring for handling-induced seizures or seizure susceptibility, as well as long-term evaluations of behavioral comorbidities of epilepsy. Inflammatory processes are evident in both models and are implicated in the pathogenesis of the observed seizures and comorbidities. A common feature of these models, based on the data so far available, is their pharmacoresistant profile. The presented data support the role of inflammatory pathways in epileptogenesis and comorbidities in two distinct epilepsy models. Pharmacoresistance is a common feature of both inflammation-based models. Utilization of these models may facilitate the identification of age-specific, syndrome- or etiology-specific therapies for the epilepsies and attendant comorbidities, including the drug-resistant forms. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Verhoeven, Willem MA; Egger, Jos IM; Knegt, Alida C; Zuydam, José; Kleefstra, Tjitske
2016-01-01
Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2) gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations) and DECIPHER (database of genomic variation and phenotype in humans using ensembl resources), so far, a total of 13 intellectually disabled patients with a genetically proven deletion of the CHD2 gene are described, of whom eleven had a history of severe forms of epilepsy starting from a young age. In this article, a moderately intellectually disabled 15-year-old male with a 15q26.1–q26.2 interstitial deletion is reported, who was referred for analysis of two recent short-lasting psychotic episodes that were nonresponsive to antipsychotic treatment and recurrent disinhibited behaviors since early infancy. Careful interdisciplinary assessment revealed that the psychotic phenomena originated from a previously unrecognized absence epilepsy. Treatment with valproic acid was started which resulted in full remission of psychotic symptoms, and consequently, substantial improvement of behavior. It was concluded that in case of (rare) developmental disorders with genetically proven etiology, a detailed inventory of anamnestic data and description of symptomatology over time may elucidate epilepsy-related psychopathology for which a specific treatment regimen is needed. PMID:27274247
Melo, Isabelle T; M Rêgo, Elisabete; Bueno, Nassib B; Gomes, Tâmara C; Oliveira, Suzana L; Trindade-Filho, Euclides M; Cabral, Cyro R; Machado, Tacy S; Galvão, Jaqueline A; R Ataide, Terezinha
2018-02-01
This study evaluated the effects of a ketogenic diet (KD) based on extra virgin coconut oil (Cocos nucifera L., VCO), on the treatment of epileptic rats. Two sets of experiments were conducted. First, male Wistar rats underwent induction of status epilepticus (SE) with the administration of pilocarpine intraperitoneally 21 animals reached spontaneous recurrent seizures (SRS) and were randomly allocated to the dietary regimens and video-monitored for 19 days. In the second experiment, 24 animals were randomized immediately after the induction of SE and followed for 67 days. Diets were as follows: Control (AIN-93G; 7% lipid), KetoTAGsoya (KD based on soybean oil; 69.79% lipid), and KetoTAGcoco (KD based on VCO; 69.79% lipid). There were no differences in the latency to the first crisis, total frequency, and duration of the SRS between groups in 2 experiments. The data suggest no effects of KD, with or without VCO, in rats with pilocarpine-induced epilepsy. © 2018 AOCS.
NASA Astrophysics Data System (ADS)
Rashid, Kashif; van der Zee, Catharina E. E. M.; Ross, Gregory M.; Chapman, C. Andrew; Stanisz, Jolanta; Riopelle, Richard J.; Racine, Ronald J.; Fahnestock, Margaret
1995-10-01
Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization.
Glucose metabolism transporters and epilepsy: only GLUT1 has an established role.
Hildebrand, Michael S; Damiano, John A; Mullen, Saul A; Bellows, Susannah T; Oliver, Karen L; Dahl, Hans-Henrik M; Scheffer, Ingrid E; Berkovic, Samuel F
2014-02-01
The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
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P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.
Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern
2017-04-03
A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.
Epilepsy surgery in children: outcomes and complications.
Kim, Seung-Ki; Wang, Kyu-Chang; Hwang, Yong-Seung; Kim, Ki Joong; Chae, Jong Hee; Kim, In-One; Cho, Byung-Kyu
2008-04-01
Ideal epilepsy surgery would eliminate seizures without causing any functional deficits. The aim of the present study was to assess seizure outcomes and complications after epilepsy surgery in children with intractable epilepsy. Data obtained in 134 children (75 boys and 59 girls) age 17 years or younger who underwent epilepsy surgery at Seoul National University Children's Hospital between 1993 and 2005 were retrospectively reviewed. Epilepsy surgery included temporal resection (59 cases), extratemporal resection (56 cases), functional hemispherectomy (7 cases), callosotomy (9 cases), multiple subpial transection (1 case), and disconnection of a hamartoma (2 cases). The mean follow-up duration was 62.3 months (range 12-168 months). The overall seizure-free rate was 69% (93 of 134 cases). The seizure-free rate was significantly higher in children who underwent temporal resection than in those in whom extratemporal resection was performed (88 vs 55%, p < 0.05). The most frequent causes of treatment failure were related to the absence of structural abnormality demonstrated on magnetic resonance imaging, development-associated disease, widespread disease documented by postoperative electroencephalography, and limited resection due to the presence of functional cortex. There were no postoperative deaths. Visual field defects were the most common complication after temporal resection (22% [13 of 59 cases]), whereas hemiparesis (mostly transient) was the most common morbidity after extratemporal resection (18% [10 of 56 cases]). Epilepsy surgery is an effective and safe therapeutic modality in childhood. In children with extratemporal epilepsy, more careful interpretation of clinical and investigative data is needed to achieve favorable seizure outcome.
Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).
Klein, Brian D; Jacobson, Catherine A; Metcalf, Cameron S; Smith, Misty D; Wilcox, Karen S; Hampson, Aidan J; Kehne, John H
2017-07-01
Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant activity at cannabinoid receptors or psychoactive effects. There is considerable interest in CBD as a therapy for epilepsy. Almost a third of epilepsy patients are not adequately controlled by clinically available anti-seizure drugs (ASDs). Initial studies appear to demonstrate that CBD preparations may be a useful treatment for pharmacoresistant epilepsy. The National Institute of Neurological Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP) investigated CBD in a battery of seizure models using a refocused screening protocol aimed at identifying pharmacotherapies to address the unmet need in pharmacoresistant epilepsy. Applying this new screening workflow, CBD was investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling models and rat MES and lamotrigine-resistant amygdala kindling models. Following intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in the acute seizure models; mouse 6 Hz 44 mA (ED 50 164 mg/kg), mouse MES (ED 50 83.5 mg/kg) and rat MES (ED 50 88.9 mg/kg). In chronic models, CBD produced dose-dependent protection in the corneal kindled mouse (ED 50 119 mg/kg) but CBD (up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala kindled rat. Motor impairment assessed in conjunction with the acute seizure models showed that CBD exerted seizure protection at non-impairing doses. The ETSP investigation demonstrates that CBD exhibits anti-seizure properties in acute seizure models and the corneal kindled mouse. However, further preclinical and clinical studies are needed to determine the potential for CBD to address the unmet needs in pharmacoresistant epilepsy.
Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.
Shrot, Shai; Ramaty, Erez; Biala, Yoav; Bar-Klein, Guy; Daninos, Moshe; Kamintsky, Lyn; Makarovsky, Igor; Statlender, Liran; Rosman, Yossi; Krivoy, Amir; Lavon, Ophir; Kassirer, Michael; Friedman, Alon; Yaari, Yoel
2014-09-02
Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Intellectual Disability and Epilepsy in Down Syndrome
BARCA, Diana; TARTA-ARSENE, Oana; DICA, Alice; ILIESCU, Catrinel; BUDISTEANU, Magdalena; MOTOESCU, Cristina; BUTOIANU, Niculina; CRAIU, Dana
2014-01-01
Down Syndrome (DS) is the most common genetic cause of mental retardation, with a reported frequency of epilepsy between 1.4-17% (1). There is a paucity of data in the literature regarding epilepsy in Down syndrome and its relation to intellectual disability. Objectives: The purpose of this article is to analyze the association of epilepsy in children with DS - frequency and type of seizures, treatment, outcome and to compare cognitive impairment of children with DS and epilepsy and DS without epilepsy from our cohort. Methods: A four years systematic retrospective analysis of the database of the Pediatric Neurology Clinic (January 2010 - December 2013) identified a cohort of 39 pediatric cases with DS and neurological symptoms, 9 of them (23%) associating epileptic seizures. Following data were analysed: clinical and neurological examination, type/s of seizures, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), psychological examination, psychiatric evaluation in selected cases, electrocardiography (ECG), cardiac ultrasonography, ophthalmologic examination. Results: 23% (9 patients) of the children with DS of our cohort presented epilepsy. Five patients had epileptic spasms (56%), one of these further developed astatic seizures. Focal seizures were observed in three patients (33%) and absence with eyelid myoclonias in one patient (11%). Two of the nine patients with DS and epilepsy had generalized seizures, both with very good response to levetiracetam (LEV). EEG was abnormal at seizure onset, and was improved after treatment. Of the nine children with DS and epilepsy, two (22%) presented mild mental retardation and seven (78%) had moderate to severe cognitive delay. Of the 30 children with DS and without epilepsy, 21 (70%) had mild mental retardation and 9 (30%) had moderate to severe cognitive impairment. Conclusions: The most frequent epileptic syndrome associated with DS is West syndrome, with good response to specific antiepileptics
Tetanus toxin as a tool for studying epilepsy.
Mellanby, J; Hawkins, C; Mellanby, H; Rawlins, J N; Impey, M E
1984-01-01
The use of tetanus toxin, injected into the hippocampus of the rat, to produce an "animal model" of chronic limbic epilepsy is described. This model has yielded information complementary to that derived from other animal models and has several important advantages: while it involves spontaneous seizures, it occurs without gross damage to the brain ; it is eventually reversible in terms of fits and the overall reappearance of the EEG. It can therefore be used to look both at the effects of ongoing epilepsy and also at the long-term changes in brain function induced by previous epilepsy. Evidence is presented that the toxin probably remains localised at the site of injection. The information which has so far been obtained with this model on the relation between epilepsy and abnormal behaviour is summarised. In particular, it appears that the epilepsy produces long-term deficits in the animals' ability to learn and remember of a sort which suggest that an enduring malfunction has been induced in the hippocampus. The significance of the findings for clinical research and for future investigation of the nature of epilepsy are described. It is emphasised that the neurotoxins may be usefully exploited not only for investigating the molecular basis of neuronal mechanisms but also for inducing long-lasting plastic changes in integrated brain function.
Impaired Consciousness in Epilepsy
Blumenfeld, Hal
2013-01-01
Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—maintains alertness, attention and awareness. Recent advances in neuroimaging, electrophysiology and prospective behavioral testing have shed new light on how epileptic seizures disrupt the consciousness system. Diverse seizure types including absence, generalized tonic-clonic and complex partial seizures converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding these mechanisms may lead to improved treatment strategies to prevent impaired consciousness and improve quality of life in people with epilepsy. PMID:22898735
Can I go out for a smoke? A nursing challenge in the epilepsy monitoring unit.
Hamilton, M; McLachlan, R S; Burneo, J G
2009-05-01
Cigarette smoking is common in patients with intractable epilepsy. As a preliminary assessment of epilepsy and smoking, we evaluated the impact of breaks for smoking on the investigation of epilepsy patients admitted to our epilepsy monitoring unit. Absences from the epilepsy unit at the London Health Sciences Center were monitored for 6 months by nursing personnel. During these absences, events that occurred were registered as well. This is possible using portable EEG recorders (XLTEK) that patients carry with them all the time. A disadvantage is that video recording is not available if the patient has a seizure outside the unit. Information was entered consecutively in a datasheet. Diagnosis, duration of hospital stay, frequency of breaks, and time outside the unit were recorded. Descriptive and statistical analysis was performed. Two thousand two hundred and ninety trips were recorded. Mean duration of stay was 10 days for smokers and 8.5 for non-smokers. Non-smokers had a total of 439 seizures of which 6 (1.4%) were not recorded, while the smokers had 213, of which 11 (5.2%) were not recorded. Five events did not have electroencephalographic correlation, raising a suspicion of non-epileptic events (pseudoseizures). Despite the low number of events missed, precious information may be lost during smoking trips by patients admitted to the epilepsy unit. Ways to avoid such trips should be implemented in epilepsy monitoring units allowing smoking breaks for patients.
Outcome of childhood-onset epilepsy from adolescence to adulthood: Transition issues.
Nabbout, R; Andrade, D M; Bahi-Buisson, N; Cross, H; Desquerre, I; Dulac, O; Granata, T; Hirsch, E; Navarro, V; Ouss, L; Pearl, P L; Schmidt, D; Thiele, E; Camfield, P R; Camfield, C S
2017-04-01
This is the second of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper addresses the outcome for some particularly challenging childhood-onset epileptic disorders with the goal of recommending the best approach to transition. We have grouped these disorders in five categories with a few examples for each. The first group includes disorders presenting in childhood that may have late- or adult-onset epilepsy (metabolic and mitochondrial disorders). The second group includes disorders with changing problems in adulthood (tuberous sclerosis complex, Rett syndrome, Dravet syndrome, and autism). A third group includes epilepsies that change with age (Childhood Absence Epilepsy, Juvenile Myoclonic Epilepsy, West Syndrome, and Lennox-Gastaut syndrome). A fourth group consists of epilepsies that vary in symptoms and severity depending on the age of onset (autoimmune encephalitis, Rasmussen's syndrome). A fifth group has epilepsy from structural causes that are less likely to evolve in adulthood. Finally we have included a discussion about the risk of later adulthood cerebrovascular disease and dementia following childhood-onset epilepsy. A detailed knowledge of each of these disorders should assist the process of transition to be certain that attention is paid to the most important age-related symptoms and concerns. Copyright © 2016 Elsevier Inc. All rights reserved.
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Intractable seizures after a lengthy remission in childhood-onset epilepsy.
Camfield, Peter R; Camfield, Carol S
2017-12-01
To establish the risk of subsequent intractable epilepsy after ≥2, ≥5, and ≥10 years of remission in childhood-onset epilepsy. From the Nova Scotia childhood-onset epilepsy population-based cohort patients with all types of epilepsy were selected with ≥20 years follow-up from seizure onset (incidence cases). Children with childhood absence epilepsy were excluded. The rate of subsequent intractable epilepsy was then studied for patients with ≥5 years remission on or off AED treatment and compared with the rate for those with ≥2 and ≥10 years of remission. Three hundred eighty-eight eligible patients had ≥20 years follow-up (average 27.7 ± (standard deviation) 4 years) until they were an average of 34 ± 6.5 years of age. Overall, 297 (77%) had a period of ≥5 years of seizure freedom (average 21.2 ± 8 years), with 90% of these remissions continuing to the end of follow-up. Seizures recurred in 31 (10%) and were intractable in 7 (2%). For the 332 with a remission of ≥2 years seizure-free, 6.9% subsequently developed intractable epilepsy (p = 0.001). For the 260 with ≥10 years remission, 0.78% subsequently developed intractable epilepsy (p = 0.25 compared with ≥5 years remission). Even after ≥5 or ≥10 years of seizure freedom, childhood-onset epilepsy may reappear and be intractable. The risk is fortunately small, but for most patients it is not possible to guarantee a permanent remission. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.
Rempe, Ralf G; Hartz, Anika M S; Soldner, Emma L B; Sokola, Brent S; Alluri, Satya R; Abner, Erin L; Kryscio, Richard J; Pekcec, Anton; Schlichtiger, Juli; Bauer, Björn
2018-05-02
The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo / ex vivo approach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findings in vivo in rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A 2 Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage. SIGNIFICANCE STATEMENT The mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A 2 , which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden. Copyright © 2018 the
Lohuis, P J; Börjesson, P K; Klis, S F; Smoorenburg, G F
2000-05-01
Circulating adrenal hormones affect strial function. Removal of endogenous levels of adrenal steroids by bilateral adrenalectomy (ADX) in rats causes a decrease of Na(+)/K(+)-ATPase activity in the cochlear lateral wall [Rarey et al., 1989. Arch. Otolaryngol. Head Neck Surg. 115, 817-821] and a decrease of the volume of the marginal cells in the stria vascularis [Lohuis et al., 1990. Acta Otolaryngol. (Stockh.) 110, 348-356]. To study further the effect of absence of circulating adrenocorticosteroids on cochlear function, 18 male Long Evans rats underwent either an ADX or a SHAM operation. Electrocochleography was performed 1 week after surgery for tone bursts in a frequency range of 1-16 kHz. Thereafter, the cochleas were harvested and examined histologically. No significant changes in the amplitude growth curves of the summating potential (SP), the compound action potential (CAP) and the cochlear microphonics (CM) were detected after ADX. However, visually, there appeared to be a decrease of endolymphatic volume (tentatively called imdrops). Reissner's membrane (RM) extended less into scala vestibuli in ADX animals than in SHAM-operated animals. The ratio between the length of RM and the straight distance between the medial and lateral attachment points of RM were used as an objective measure to quantify this effect in each sub-apical half turn of the cochlea. The decrease in length of RM was statistically significant. Thus, circulating adrenal hormones appear to be necessary for normal cochlear fluid homeostasis. Absence of one or more of these hormones leads to shrinkage of the scala media (imdrops). However, the absence of adrenal hormones does not affect the gross cochlear potentials. Apparently, the cochlea is capable of compensating for the absence of circulating adrenal hormones to sustain the conditions necessary for proper cochlear transduction.
Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures.
Lhatoo, Samden D; Nei, Maromi; Raghavan, Manoj; Sperling, Michael; Zonjy, Bilal; Lacuey, Nuria; Devinsky, Orrin
2016-07-01
To describe the phenomenology of monitored sudden unexpected death in epilepsy (SUDEP) occurring in the interictal period where death occurs without a seizure preceding it. We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death. Three patients (two definite and one probable) had SUDEP. They had a typical high SUDEP risk profile with longstanding intractable epilepsy and frequent generalized tonic-clonic seizures (GTCS). All patients had varying patterns of respiratory and bradyarrhythmic cardiac dysfunction with profound electroencephalography (EEG) suppression. In two patients, patterns of cardiorespiratory failure were similar to those seen in some patients in the Mortality in Epilepsy Monitoring Units Study (MORTEMUS). SUDEP almost always occur postictally, after GTCS and less commonly after a partial seizure. Monitored SUDEP or near-SUDEP cases without a seizure have not yet been reported in literature. When nonmonitored SUDEP occurs in an ambulatory setting without an overt seizure, the absence of EEG information prevents the exclusion of a subtle seizure. These cases confirm the existence of nonseizure SUDEP; such deaths may not be prevented by seizure detection-based devices. SUDEP risk in patients with epilepsy may constitute a spectrum of susceptibility wherein some are relatively immune, death occurs in others with frequent GTCS with one episode of seizure ultimately proving fatal, while in others still, death may occur even in the absence of a seizure. We emphasize the heterogeneity of SUDEP phenomena. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Theories of Impaired Consciousness in Epilepsy
Yu, Lissa; Blumenfeld, Hal
2015-01-01
Although the precise mechanisms for control of consciousness are not fully understood, emerging data show that conscious information processing depends on the activation of certain networks in the brain and that the impairment of consciousness is related to abnormal activity in these systems. Epilepsy can lead to transient impairment of consciousness, providing a window into the mechanisms necessary for normal consciousness. Thus, despite differences in behavioral manifestations, cause, and electrophysiology, generalized tonic–clonic, absence, and partial seizures engage similar anatomical structures and pathways. We review prior concepts of impaired consciousness in epilepsy, focusing especially on temporal lobe complex partial seizures, which are a common and debilitating form of epileptic unconsciousness. We discuss a “network inhibition hypothesis” in which focal temporal lobe seizure activity disrupts normal cortical–subcortical interactions, leading to depressed neocortical function and impaired consciousness. This review of the major prior theories of impaired consciousness in epilepsy allows us to put more recent data into context and to reach a better understanding of the mechanisms important for normal consciousness. PMID:19351355
Kros, Lieke; Lindeman, Sander; Eelkman Rooda, Oscar H. J.; Murugesan, Pavithra; Bina, Lorenzo; Bosman, Laurens W. J.; De Zeeuw, Chris I.; Hoebeek, Freek E.
2017-01-01
Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive. Here, we investigated to what extent modulation of complex spike firing is reflected in the temporal patterns of seizures. Extracellular single-unit recordings in awake, head-restrained homozygous tottering mice, which suffer from a mutation in the voltage-gated CaV2.1 calcium channel, revealed that a substantial proportion of Purkinje cells (26%) showed increased complex spike activity and rhythmicity during GSWDs. Moreover, Purkinje cells, recorded either electrophysiologically or by using Ca2+-imaging, showed a significant increase in complex spike synchronicity for both adjacent and remote Purkinje cells during ictal events. These seizure-related changes in firing frequency, rhythmicity and synchronicity were most prominent in the lateral cerebellum, a region known to receive cerebral input via the inferior olive. These data indicate profound and widespread changes in olivary firing that are most likely induced by seizure-related activity changes in the thalamocortical network, thereby highlighting the possibility that olivary neurons can compensate for pathological brain-state changes by dampening oscillations. PMID:29163057
Ristić, Aleksandar J; Jovanović, Olja; Popadić, Dragan; Pađen, Višnja; Moosa, Ahsan N V; Krivokapić, Ana; Parojčić, Aleksandra; Berisavac, Ivana; Ilanković, Andrej; Baščarević, Vladimir; Vojvodić, Nikola; Sokić, Dragoslav
2017-12-01
Using a group of young healthy individuals and patients with multiple sclerosis (pMS), we aimed to investigate whether the physical attractiveness judgment affects perception of epilepsy. We tested hypothesis that subjects, in the absence of relevant clues, would catch upon the facial attractiveness when asked to speculate which person suffers epilepsy and select less attractive choices. Two photo-arrays (7 photos for each gender) selected from the Chicago Face Database (180 neutral faces of Caucasian volunteers with unknown medical status) were shown to study participants. Photos were evenly distributed along a continuum of attractiveness that was estimated by independent raters in prestudy stage. In each photo-array, three photos had rating 1-3 (unattractive), one photo had rating 4 (neutral), and three photos had rating 5-7 (attractive). High-quality printed photo-arrays were presented to test subjects, and they were asked to select one person from each photo-array "who has epilepsy". Finally, all subjects were asked to complete questionnaire of self-esteem and 19-item Scale of stereotypes toward people with epilepsy. In total, 71 students of psychology, anthropology, or andragogy (mean age: 21.6±1.7years; female: 85.9%) and 70 pMS (mean age: 37.9±8years; female: 71.4%) were tested. Majority of students or pMS had no previous personal experience with individuals with epilepsy (63.4%; 47.1%, p=0.052). Male photo was selected as epileptic in the following proportions: students - 84.5% unattractive, 8.5% neutral, and 7% attractive; pMS - 62.9% unattractive, 8.6% neutral, and 28.6% attractive (p=0.003). Female photo was selected as epileptic in the following proportions: students - 38% unattractive, 52.1% neutral, and 9.9% attractive; pMS - 32.9% unattractive, 34.3% neutral, and 32.9% attractive (0.003). Both groups showed very low potential for stigmatization: significantly lower in pMS in 10 items. Patients with multiple sclerosis showed significantly higher
Familial aggregation of focal seizure semiology in the Epilepsy Phenome/Genome Project.
Tobochnik, Steven; Fahlstrom, Robyn; Shain, Catherine; Winawer, Melodie R
2017-07-04
To improve phenotype definition in genetic studies of epilepsy, we assessed the familial aggregation of focal seizure types and of specific seizure symptoms within the focal epilepsies in families from the Epilepsy Phenome/Genome Project. We studied 302 individuals with nonacquired focal epilepsy from 149 families. Familial aggregation was assessed by logistic regression analysis of relatives' traits (dependent variable) by probands' traits (independent variable), estimating the odds ratio for each symptom in a relative given presence vs absence of the symptom in the proband. In families containing multiple individuals with nonacquired focal epilepsy, we found significant evidence for familial aggregation of ictal motor, autonomic, psychic, and aphasic symptoms. Within these categories, ictal whole body posturing, diaphoresis, dyspnea, fear/anxiety, and déjà vu/jamais vu showed significant familial aggregation. Focal seizure type aggregated as well, including complex partial, simple partial, and secondarily generalized tonic-clonic seizures. Our results provide insight into genotype-phenotype correlation in the nonacquired focal epilepsies and a framework for identifying subgroups of patients likely to share susceptibility genes. © 2017 American Academy of Neurology.
[Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].
Jóźwiak, Sergiusz
2007-01-01
Epilepsy is one of the most frequent neurological disorders, both in children and adult persons. About 0.5-1% of general population suffer from epilepsy, which means that about 50 million people in the world are affected. First years of life and very late adulthood are periods in human's life particularly predisposing to epilepsy. Repetitive epileptic seizures may cause many life-threatening situations and significantly lower patient's quality of life. To the most serious complications belong status epilepticus and sudden unexpected deaths due to epilepsy (SUDEP). Absences from work or school caused by seizures, difficulties in social life, frequent injuries and necessity of polytherapy are also important for patients. All these factors result in low self-esteem and poor quality of life. The main aim of the treatment was control of epileptic seizures. However, despite of new antiepileptic drugs developed almost every year, in one third of all patients with epilepsy seizures remain out of control. Those patients are regarded to have "drug-resistant epilepsy". Despite of significant scale of the problem, there is no one definition of the phenomenon. In the presented review the authors outline current definitions, recent opinions on pathogenesis and risk factors, and provide practical rules of pharmacotherapy of epilepsy, which should help to restrict drug-resistancy.
Atanasova, Dimitrinka; Tchekalarova, Jana; Ivanova, Natasha; Nenchovska, Zlatina; Pavlova, Ekaterina; Atanassova, Nina; Lazarov, Nikolai
2018-01-15
Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT 1 receptor) in limbic structures, as well as the effect of the AT1 receptor antagonist losartan in a model of comorbid hypertension and epilepsy. The expression of AT 1 receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE). The effect of losartan was studied on AT 1 receptor expression in epileptic rats that were treated for a period of 4weeks after status epilepticus. The naive and epileptic SHRs were characterized by stronger protein expression of AT 1 receptor than normotensive Wistar rats in the CA1, CA3a, CA3b, CA3c field and the hilus of the dentate gyrus of the dorsal hippocampus but fewer cells were immunostained in the piriform cortex. Increased AT 1 immunostaining was observed in the basolateral amygdala of epileptic SHRs but not of epileptic Wistar rats. Losartan exerted stronger and structure-dependent suppression of AT 1 receptor expression in SHRs compared to Wistar rats. Our results confirm the important role of AT 1 receptor in epilepsy and suggest that the AT 1 receptor antagonists could be used as a therapeutic strategy for treatment of comorbid hypertension and epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.
Perirhinal cortex and temporal lobe epilepsy
Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo
2013-01-01
The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554
Epilepsy in children with subacute sclerosing panencephalitis.
Jović, Nebojša J
2013-01-01
Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Retrospective study was carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years). SSPE onset ranged from 4.5 to 16.5 years (mean 10.05). Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6%) cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.
Seizure drawings: insight into the self-image of children with epilepsy.
Stafstrom, Carl E; Havlena, Janice
2003-02-01
Epilepsy is a chronic disorder that is associated with numerous psychological challenges, especially in children. Drawings have been underutilized as a method to obtain insight into psychological issues in children with epilepsy. We asked 105 children with epilepsy, ages 5 to 18 years, to draw a picture of what it is like to have a seizure. Across ages and epilepsy syndromes, the drawings showed evidence of impaired self-concept, low self-esteem, and a sense of helplessness and vulnerability. Overall, the drawings of human figures were less developed than expected for chronological age. In some drawings, indicators of underlying depression were found. When considered by epilepsy syndrome or seizure type, some specific artistic features were noted. Children with simple partial (motor) seizures drew distorted body parts, especially limbs. Those with complex partial seizures depicted sensory symptoms and mental status changes such as confusion. Children with generalized tonic-clonic seizures showed shaking extremities. Drawings by children with absence seizures illustrated mainly staring. In conclusion, drawings are a powerful method to examine the self-concept of children with epilepsy and gain insight into their feelings about themselves and their world.
The molecular and phenotypic spectrum of IQSEC2-related epilepsy.
Zerem, Ayelet; Haginoya, Kazuhiro; Lev, Dorit; Blumkin, Lubov; Kivity, Sara; Linder, Ilan; Shoubridge, Cheryl; Palmer, Elizabeth Emma; Field, Michael; Boyle, Jackie; Chitayat, David; Gaillard, William D; Kossoff, Eric H; Willems, Marjolaine; Geneviève, David; Tran-Mau-Them, Frederic; Epstein, Orna; Heyman, Eli; Dugan, Sarah; Masurel-Paulet, Alice; Piton, Ame'lie; Kleefstra, Tjitske; Pfundt, Rolph; Sato, Ryo; Tzschach, Andreas; Matsumoto, Naomichi; Saitsu, Hirotomo; Leshinsky-Silver, Esther; Lerman-Sagie, Tally
2016-11-01
IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vadasz, C.; Fleischer, A.; Carpi, D.
1995-02-27
Neocortical high-voltage spike-and-wave discharges (HVS) in the rat are an animal model of petit mal epilepsy. Genetic analysis of total duration of HVS (s/12 hr) in reciprocal F1 and F2 hybrids of F344 and BN rats indicated that the phenotypic variability of HVS cannot be explained by simple, monogenic Mendelian model. Biometrical analysis suggested the presence of additive, dominance, and sex-linked-epistatic effects, buffering maternal influence, and heterosis. High correlation was observed between average duration (s/episode) and frequency of occurrence of spike-and-wave episodes (n/12 hr) in parental and segregating generations, indicating that common genes affect both duration and frequency of themore » spike-and-wave pattern. We propose that both genetic and developmental - environmental factors control an underlying quantitative variable, which, above a certain threshold level, precipitates HVS discharges. These findings, together with the recent availability of rat DNA markers for total genome mapping, pave the way to the identification of genes that control the susceptibility of the brain to spike-and-wave discharges. 67 refs., 3 figs., 5 tabs.« less
O'Toole, Stephanie; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K
2016-04-01
The aim of this qualitative study was to explore the challenges that parents of children with epilepsy experienced when engaging in dialog with their child about epilepsy and epilepsy-related issues. Using a qualitative exploratory approach, interviews were conducted with 34 parents of children with epilepsy (aged 6-16 years), consisting of 27 mothers and 7 fathers. Data were transcribed verbatim and thematically analyzed. Findings revealed five main themes: normalizing epilepsy, the invisibility of epilepsy, information concealment, fear of misinforming the child, and difficulty in discussing particular epilepsy-related issues. Many of the communicative challenges experienced by parents impacted on their ability to engage openly in parent-child dialog about epilepsy in the home. Parents face specific challenges when choosing to communicate with their child about epilepsy, relating to creating a sense of normality, reducing fear of causing their child worry, and having a lack of epilepsy-related knowledge. Healthcare professionals who work closely with families living with epilepsy should remain mindful of the importance of discussing family communication surrounding epilepsy and the challenges parents of children with epilepsy face when talking about epilepsy within the home. Copyright © 2016 Elsevier Inc. All rights reserved.
Basic knowledge of epilepsy among medical students.
Tiamkao, Siriporn; Tiamkao, Somsak; Auevitchayapat, Narong; Arunpongpaisal, Suwanna; Chaiyakum, Aporanee; Jitpimolmard, Suthipun; Phuttharak, Warinthorn; Phunikhom, Kutcharin; Saengsuwan M, Jiamjit; Vannaprasaht, Suda
2007-11-01
The medical students' knowledge about basic medical neuroscience in the preclinical level may be fragmented and incomplete. Evaluate the knowledge of students prior to a lecture on epilepsy in clinical level. One hundred ten fourth-year medical students' knowledge was accessed by a self-administered questionnaire. The presented results revealed that 91.8% of respondents knew that epilepsy arose from a transient dysfunction in the brain. Generalized tonic-clonic seizures (GTCs) were the most common type (91.5%) they knew and absence seizures were the least common type (33.6%) they knew. All of them knew that eating pork and punishment of gods did not cause epilepsy. However 50% thought that genetics was a cause and 80.3% did not know that stroke and sleep deprivation (92.7%) cause epilepsy. About treatment and prognosis, only 28.2% of respondents thought epilepsy can be cured and patients should take antiepileptic drugs (AEDs) for seizure free 2-5 years (48.2%), life long (33.6%). They knew that the patients should be prohibited from driving (80%), working on machinery (74.5%), and (27.3%) avoid drinking. However, they knew that the patients could marry (100%), get pregnant (98.2%), and lactate (91.9%). Regarding the first aid management, 50.9% of them recommended that placing a piece of wood between the teeth during a seizure and perform chest compressions (20.0%). Means knowledge scores is about 60%, the highest score is the definition of epilepsy (90.2%) and the lowest is type of seizure (43%). The findings indicated that lecturers should review aspects ofpathophysiology and emphasize on type of seizure, cause, consequences, and prognosis including first-aid management.
Resources - epilepsy ... The following organizations are good resources for information on epilepsy : Epilepsy Foundation -- www.epilepsy.com National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/ ...
Prevett, M C; Cunningham, V J; Brooks, D J; Fish, D R; Duncan, J S
1994-09-01
The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes.
Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3.
Korenke, Georg-Christoph; Eggert, Marlene; Thiele, Holger; Nürnberg, Peter; Sander, Thomas; Steinlein, Ortrud K
2016-03-01
Mutations in NPRL3, one of three genes that encode proteins of the mTORC1-regulating GATOR1 complex, have recently been reported to cause cortical dysplasia with focal epilepsy. We have now analyzed a multiplex epilepsy family by whole exome sequencing and identified a frameshift mutation (NM_001077350.2; c.1522delG; p.E508Rfs*46) within exon 13 of NPRL3. This truncating mutation causes an epilepsy phenotype characterized by early childhood onset of mainly nocturnal frontal lobe epilepsy. The penetrance in our family was low (three affected out of six mutation carriers), compared to families with either ion channel- or DEPDC5-associated familial nocturnal frontal lobe epilepsy. The absence of apparent structural brain abnormalities suggests that mutations in NPRL3 are not necessarily associated with focal cortical dysplasia but might be able to cause epilepsy by different, yet unknown pathomechanisms. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Depression and genetic causal attribution of epilepsy in multiplex epilepsy families.
Sorge, Shawn T; Hesdorffer, Dale C; Phelan, Jo C; Winawer, Melodie R; Shostak, Sara; Goldsmith, Jeff; Chung, Wendy K; Ottman, Ruth
2016-10-01
Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients' psychological responses and coping strategies, but little is known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that among members of families containing multiple individuals with epilepsy, depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause. A self-administered survey was completed by 417 individuals in 104 families averaging 4 individuals with epilepsy per family. Current depression was measured with the Patient Health Questionnaire. Genetic causal attribution was assessed by three questions addressing the following: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual's epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biologic relatives without epilepsy, and 3.9% in 51 individuals married into the families. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biologic relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p = 0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in families containing
Medel-Matus, Jesús-Servando; Shin, Don; Sankar, Raman; Mazarati, Andrey
2017-12-01
Anxiety is one of the most common comorbidities of epilepsy, which has major detrimental effects on the quality of life. Generalized anxiety disorder (GAD) associated with epilepsy has been receiving most attention. However, several other forms of anxiety reportedly present in patients with epilepsy, including panic disorder (PD). In this study, using an animal model of limbic epilepsy, we examined the interplay between epilepsy and panic-like behavior (PLB). Further, considering the high degree of comorbidity between depression on the one hand, and both epilepsy and PD on the other hand, we studied whether and how the presence of PLB in animals with epilepsy would affect their performance in depression-relevant tests. Fifty-day-old male Wistar rats were subjected to repeated alternating electrical stimulations of the basolateral amygdala (BLA) to induce kindling of limbic seizures, and the dorsal periaqueductal gray (DPAG) to induce panic-like episodes. Seizure susceptibility and panic reaction threshold were examined before the first and 24h after the last stimulation. At the end of the stimulations, the rats were examined in depression-relevant tests: saccharin preference test (SPT) for anhedonia and forced swimming test (FST) for despair/hopelessness. With regard to kindling, BLA+DPAG stimulation induced more profound increase of seizure susceptibility than BLA stimulation alone (evident as the reduction of the afterdischarge threshold and the increase of the afterdischarge duration). With regard to PLB, the BLA+DPAG stimulation exacerbated the severity of panic-like episodes, as compared with the DPAG stimulation alone. Basolateral amygdala stimulation alone had no effects on panic-like reactions, and DPAG stimulation alone did not modify kindling epileptogenesis. Combined stimulation of BLA and DPAG induced depressive-like behavioral impairments. This is the first experimental study showing bidirectional, mutually exacerbating effect of epilepsy and PLB, and
Depression and Genetic Causal Attribution of Epilepsy in Multiplex Epilepsy Families
Sorge, Shawn T.; Hesdorffer, Dale C.; Phelan, Jo C.; Winawer, Melodie R.; Shostak, Sara; Goldsmith, Jeff; Chung, Wendy K.; Ottman, Ruth
2016-01-01
Summary Objectives Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients’ psychological responses and coping strategies, but little is currently known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause among members of families containing multiple individuals with epilepsy. Methods A self-administered survey was completed by 417 individuals in 104 families averaging four individuals with epilepsy per family. Current depression was measured with the PHQ-9. Genetic causal attribution was assessed by three questions addressing: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual’s epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. Results Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biological relatives without epilepsy, and 3.9% in 51 married-in individuals. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biological relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p=0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. Significance Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in
Maia, Gisela H; Brazete, Cátia S; Soares, Joana I; Luz, Liliana L; Lukoyanov, Nikolai V
2017-09-01
Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pretreating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5mg/kg, 9.0mg/kg or 12.5mg/kg. A single dose of 6.5mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.
Teaching the Student with Epilepsy: A Dilemma or an Opportunity.
ERIC Educational Resources Information Center
Walton, Ann Viva
The paper looks at epilepsy, with emphasis on student problems and the role of the teacher. Initial sections describe characteristics of absence seizures, generalized tonic-clonic (grand mal) seizures, and complex partial seizures. The educator's role is considered relating to three areas: medical problems, social problems, and psychological…
Wagner, Adam P; Croudace, Tim J; Bateman, Naomi; Pennington, Mark W; Prince, Elizabeth; Redley, Marcus; White, Simon R; Ring, Howard
2017-01-01
Intellectual disability (ID) is relatively common in people with epilepsy, with prevalence estimated to be around 25%. Surprisingly, given this relatively high frequency, along with higher rates of refractory epilepsy than in those without ID, little is known about outcomes of different management approaches/clinical services treating epilepsy in adults with ID-we investigate this area. We undertook a naturalistic observational cohort study measuring outcomes in n = 91 adults with ID over a 7-month period (recruited within the period March 2008 to April 2010). Participants were receiving treatment for refractory epilepsy (primarily) in one of two clinical service settings: community ID teams (CIDTs) or hospital Neurology services. The pattern of comorbidities appeared important in predicting clinical service, with Neurologists managing the epilepsy of relatively more of those with neurological comorbidities whilst CIDTs managed the epilepsy of relatively more of those with psychiatric comorbidities. Epilepsy-related outcomes, as measured by the Glasgow Epilepsy Outcome Scale 35 (GEOS-35) and the Epilepsy and Learning Disabilities Quality of Life Scale (ELDQoL) did not differ significantly between Neurology services and CIDTs. In the context of this study, the absence of evidence for differences in epilepsy-related outcomes amongst adults with ID and refractory epilepsy between mainstream neurology and specialist ID clinical services is considered. Determining the selection of the service managing the epilepsy of adults with an ID on the basis of the skill sets also required to treat associated comorbidities may hence be a reasonable heuristic.
Italian Wikipedia and epilepsy: An infodemiological study of online information-seeking behavior.
Brigo, Francesco; Lattanzi, Simona; Giussani, Giorgia; Tassi, Laura; Pietrafusa, Nicola; Galimberti, Carlo Andrea; Nardone, Raffaele; Bragazzi, Nicola Luigi; Mecarelli, Oriano
2018-04-01
Wikipedia is the most commonly accessed source of health information by both healthcare professionals and the lay public worldwide. We aimed to evaluate information-seeking behavior of Internet users searching the Italian Wikipedia for articles related to epilepsy and its treatment. Using Pageviews Analysis, we assessed the total and mean monthly views of articles from the Italian Wikipedia devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs (AEDs) from January 1, 2015 to October 31, 2017. We compared the views of the article on epilepsy with those of articles focusing on Alzheimer's disease, migraine, multiple sclerosis, syncope, and stroke and adjusted all results for crude disease prevalence. With the only exception of the article on multiple sclerosis, the adjusted views for the Italian Wikipedia article on epilepsy were higher than those for the other neurological disorders. The most viewed articles on seizure type were devoted to tonic-clonic seizure, typical absence seizure, tonic convulsive seizures, and clonic convulsive seizures. The most frequently accessed articles on epilepsy syndromes were about temporal lobe epilepsy and Lennox-Gastaut syndrome. The most frequently viewed articles on AEDs were devoted to valproic acid, carbamazepine, and levetiracetam. Wikipedia searches seem to mirror patients' fears and worries about epilepsy more than its actual epidemiology. The ultimate reasons for searching online remain unknown. Epileptologists and epilepsy scientific societies should make greater efforts to work jointly with Wikipedia to convey more accurate and up-to-date information about epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.
Challenges in the pharmacological management of epilepsy and its causes in the elderly.
Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Aguglia, Umberto
2016-04-01
Epilepsy represents the third most common neurological disorders in the elderly after cerebrovascular disorders and dementias. The incidence of new-onset epilepsy peaks in this age group. The most peculiar aetiologies of late-onset epilepsy are stroke, dementia, and brain tumours. However, aetiology remains unknown in about half of the patients. Diagnosis of epilepsy may be challenging due to the frequent absence of ocular witnesses and the high prevalence of seizure-mimics (i.e. transient ischemic attacks, syncope, transient global amnesia or vertigo) in the elderly. The diagnostic difficulties are even greater when patients have cognitive impairment or cardiac diseases. The management of late-onset epilepsy deserves special considerations. The elderly can reach seizure control with low antiepileptic drugs (AEDs) doses, and seizure-freedom is possible in the vast majority of patients. Pharmacological management should take into account pharmacokinetics and pharmacodynamics of AEDs and the frequent occurrence of comorbidities and polytherapy in this age group. Evidences from double-blind and open-label studies indicate lamotrigine, levetiracetam and controlled-release carbamazepine as first line treatment in late-onset epilepsy. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pennacchio, Paolo; Noé, Francesco; Gnatkovsky, Vadym; Moroni, Ramona Frida; Zucca, Ileana; Regondi, Maria Cristina; Inverardi, Francesca; de Curtis, Marco; Frassoni, Carolina
2015-09-01
Cortical dysplasias (CDs) represent a wide range of cortical abnormalities that closely correlate with intractable epilepsy. Rats prenatally exposed to 1-3-bis-chloroethyl-nitrosurea (BCNU) represent an injury-based model that reproduces many histopathologic features of human CD. Previous studies reported in vivo hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. To determine whether cortical and hippocampal lesions lead to epileptiform discharges and/or seizures in the BCNU model, rats at three different ages (3, 5, and 9 months old) were implanted for long-term video electroencephalographic recording. At the end of the recording session, brain tissue was processed for histologic and immunohistochemical investigation including cAMP response element binding protein (CREB) phosphorylation, as a biomarker of epileptogenicity. BCNU-treated rats showed spontaneous epileptiform activity (67%) in the absence of a second seizure-provoking hit. Such activity originated mainly from one hippocampus and propagated to the ipsilateral neocortex. No epileptiform activity was found in age-matched control rats. The histopathologic investigation revealed that all BCNU rats with epileptiform activity showed neocortical and hippocampal abnormalities; the presence and the severity of these lesions did not correlate consistently with the propensity to generate epileptiform discharges. Epileptiform activity was found only in cortical areas of BCNU-treated rats in which a correlation between brain abnormalities and increased pCREB expression was observed. This study demonstrates the in vivo occurrence of spontaneous epileptiform discharges in the BCNU model and shows that increased pCREB expression can be utilized as a reliable biomarker of epileptogenicity. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Chi, Xiaosa; Huang, Cheng; Li, Rui; Wang, Wei; Wu, Mengqian; Li, Jinmei; Zhou, Dong
2017-04-01
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin. Non-responders were treated for 4 weeks with vehicle only or with the mTOR pathway inhibitor rapamycin at doses of 1, 3, and 6 mg/kg. Western blotting and immunohistochemistry were used to detect the expression of phospho-S6 (P-S6) and P-gp at different time points (1 h, 8 h, 1 day, 3 days, 1 weeks, 2 weeks, and 4 weeks) after the onset of treatment. Overexpression of P-S6 and P-gp was detected in both refractory mTLE patients and non-responder rats. Rapamycin showed an inhibitory effect on P-S6 and P-gp expression 1 week after treatment in rats. In addition, the expression levels of P-S6 and P-gp in the 6 mg/kg group were significantly lower than those in the 1 mg/kg or the 3 mg/kg group at the same time points (all P < 0.05). Moreover, rapamycin decreased the duration and number of CL-induced seizures, as well as the stage of non-responders (all P < 0.05). The current study indicates that the mTOR signaling pathway plays a critical role in P-gp expression in drug-resistant epilepsy. Inhibition of the mTOR pathway by rapamycin may be a potential therapeutic approach for pharmacoresistant epilepsy.
Managing Epilepsy Well: Emerging e-Tools for epilepsy self-management.
Shegog, Ross; Bamps, Yvan A; Patel, Archna; Kakacek, Jody; Escoffery, Cam; Johnson, Erica K; Ilozumba, Ukwuoma O
2013-10-01
The Managing Epilepsy Well (MEW) Network was established in 2007 by the Centers for Disease Control and Prevention Epilepsy Program to expand epilepsy self-management research. The network has employed collaborative research strategies to develop, test, and disseminate evidence-based, community-based, and e-Health interventions (e-Tools) for epilepsy self-management for people with epilepsy, caregivers, and health-care providers. Since its inception, MEW Network collaborators have conducted formative studies (n=7) investigating the potential of e-Health to support epilepsy self-management and intervention studies evaluating e-Tools (n=5). The MEW e-Tools (the MEW website, WebEase, UPLIFT, MINDSET, and PEARLS online training) and affiliated e-Tools (Texting 4 Control) are designed to complement self-management practices in each phase of the epilepsy care continuum. These tools exemplify a concerted research agenda, shared methodological principles and models for epilepsy self-management, and a communal knowledge base for implementing e-Health to improve quality of life for people with epilepsy. © 2013.
[Eponyms and epilepsy (history of Eastern civilizations)].
Janković, S M; Sokić, D V; Lević, Z M; Susić, V; Drulović, J; Stojsavljević, N; Veskov, R; Ivanus, J
1996-01-01
The history of eponyms for epilepsy in the lands of the Eastern globe present the portrait of the attitudes of both the laymen and skilled people towards the disease and patient, as well as to the Nature itself. As opposed to the West which during the Middle ages changed its concepts of epilepsy as the organic brain disease for the sublime 'alchemic' position, the people of the East were more prone to consider from the beginning of their civilization till the XIX century that epilepsy is the consequence of the evanescent spiritual and extracorporal forces which by themselves were out of their reach. As compared to the western civilization, the historical resources are, often as a consequence of a linguistic barriers, more scarce-as consequently is the number of eponyms, but are nevertheless picturesque. The medical science from Babylonian period presumed that epileptic manifestations are the consequence of the demonic or ill spiritual actions. There existed an attitude that at the beginning of an epileptic attack the patient was possessed by a demon (the Akkadic, i.e., Babylonian verb "sibtu" denoting epilepsy, had the meaning "to seize" or "to be obsessed"); at the end of the clonic phase the demon departed from the body. Different demons were responsible for different forms of epilepsy such as nocturnal and children epilepsy, absence epilepsy and pure convulsions, simple and complex automatisms, and gelastic epilepsy. Thus, the doctors from the period of Babylon aside from making primordial classification of epilepsies, knew about their clinical picture (prodromal symptoms and aura, Jackson's epilepsy. Todd's paralysis), postictal phenomena and intericatl emotional instability; provocative factors were also known (sleep deprivation, emotions, as well as alcohol, albeit in a negative sense-as a cure for epilepsy). There is no doubt than in the period of Babylon the clinical picture of serial fits and its progress to status epilepticus were clearly recognized and
Clinical aspects of juvenile myoclonic epilepsy.
Genton, Pierre; Thomas, Pierre; Kasteleijn-Nolst Trenité, Dorothee G A; Medina, Marco Tulio; Salas-Puig, Javier
2013-07-01
Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise. Copyright © 2013. Published by Elsevier Inc.
Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).
Rektor, Ivan; Schachter, Steven C; Arzy, Shahar; Baloyannis, Stavros J; Bazil, Carl; Brázdil, Milan; Engel, Jerome; Helmstaedter, Gerhard; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kesner, Ladislav; Komárek, Vladimír; Krämer, Günter; Leppik, Ilo E; Mann, Michael W; Mula, Marco; Risse, Gail L; Stoker, Guy W; Kasteleijn-Nolst Trenité, Dorothée G A; Trimble, Michael; Tyrliková, Ivana; Korczyn, Amos D
2013-08-01
Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art. Copyright © 2013. Published by Elsevier Inc.
G., Visweswari; K., Siva Prasad; V., Lokanatha; Rajendra, W.
2010-01-01
Background: To study the anticonvulsant effect of different extracts of Centella asiatica (CA) in male albino rats with reference to Na+/K+, Mg2+ and Ca2+-ATPase activities. Materials and Methods: Male Wistar rats (150±25 g b.w.) were divided into seven groups of six each i.e. (a) control rats treated with saline, (b) pentylenetetrazol (PTZ)-induced epileptic group (60 mg/kg, i.p.), (c) epileptic group pretreated with n-hexane extract (n-HE), (d) epileptic group pretreated with chloroform extract (CE), (e) epileptic group pretreated with ethyl acetate extract (EAE), (f) epileptic group pretreated with n-butanol extract (n-BE), and (g) epileptic group pretreated with aqueous extract (AE). Results: The activities of three ATPases were decreased in different regions of brain during PTZ-induced epilepsy and were increased in epileptic rats pretreated with different extracts of CA except AE. Conclusion: The extracts of C. asiatica, except AE, possess anticonvulsant and neuroprotective activity and thus can be used for effective management in treatment of epileptic seizures. PMID:20711371
Specht, Ulrich; Coban, Ingrid; Bien, Christian G; May, Theodor W
2015-10-01
The purpose of this study was to assess the risk factors for early disability pension (EDP) in adult patients with epilepsy in a specialized epilepsy rehabilitation setting. In a retrospective study, 246 patients with epilepsy and employment difficulties leading to referral to an inpatient rehabilitation unit were evaluated with a questionnaire on admission and after a mean of 2.5years after discharge. Patients already receiving EDP at baseline were excluded. Epilepsy-related, demographic, and employment-related data as well as cognitive functioning and psychiatric comorbidity were assessed as risk factors for EDP at follow-up and analyzed using logistic regression models. Seventy-six percent of the patients had uncontrolled epilepsy, and 66.7% had psychiatric comorbidity. At follow-up, 33.7% received an EDP. According to multivariate logistic regression analysis, age>50years (odds ratio (OR) 5.44, compared to age<30years), application for an EDP prior to admission (OR 3.7), sickness absence>3months in the previous year (OR 3.30, compared to sickness absence<3months), and psychiatric comorbidity (OR 2.79) were significant risk factors for an EDP at follow-up, while epilepsy-related factors and cognitive impairment showed an effect only in the univariate analyses. Potential risk factors for EDP in patients with epilepsy were evaluated using multivariate analysis. Knowledge of such factors may help to develop appropriate criteria for rehabilitation candidacy and interventions to reduce the risk for EDP. This might lead to an amelioration of both psychosocial burden of patients and economic burden on society. Copyright © 2015 Elsevier Inc. All rights reserved.
Validation of reference genes for quantitative gene expression analysis in experimental epilepsy.
Sadangi, Chinmaya; Rosenow, Felix; Norwood, Braxton A
2017-12-01
To grasp the molecular mechanisms and pathophysiology underlying epilepsy development (epileptogenesis) and epilepsy itself, it is important to understand the gene expression changes that occur during these phases. Quantitative real-time polymerase chain reaction (qPCR) is a technique that rapidly and accurately determines gene expression changes. It is crucial, however, that stable reference genes are selected for each experimental condition to ensure that accurate values are obtained for genes of interest. If reference genes are unstably expressed, this can lead to inaccurate data and erroneous conclusions. To date, epilepsy studies have used mostly single, nonvalidated reference genes. This is the first study to systematically evaluate reference genes in male Sprague-Dawley rat models of epilepsy. We assessed 15 potential reference genes in hippocampal tissue obtained from 2 different models during epileptogenesis, 1 model during chronic epilepsy, and a model of noninjurious seizures. Reference gene ranking varied between models and also differed between epileptogenesis and chronic epilepsy time points. There was also some variance between the four mathematical models used to rank reference genes. Notably, we found novel reference genes to be more stably expressed than those most often used in experimental epilepsy studies. The consequence of these findings is that reference genes suitable for one epilepsy model may not be appropriate for others and that reference genes can change over time. It is, therefore, critically important to validate potential reference genes before using them as normalizing factors in expression analysis in order to ensure accurate, valid results. © 2017 Wiley Periodicals, Inc.
Guo, Xiao-Qian; Cao, Yu-Ling; Hao, Fang; Yan, Zhong-Rui; Wang, Mei-Ling; Liu, Xue-Wu
2017-09-01
Epilepsy is complex neural disarray categorized by recurring seizures. Despite recent advances in pharmacotherapies for epilepsy, its treatment remains a challenge due to the contrary effects of the drugs. As a result, the identification of novel anti-epileptic drugs (AEDs) with neuroprotective properties and few side effects is of great value. Thus, the present study assessed the treatment effects of tangeretin using a rat model of pilocarpine-induced epilepsy. Separate groups of male Wistar rats received oral administrations of tangeretin at 50, 100, or 200mg/kg for 10 days and then, on the 10th day, they received an intraperitoneal injection of pilocarpine (30mg/kg). Subsequently, neuronal degeneration and apoptosis were assessed using Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay procedures. Additionally, the expressions of phosphatidylinositol-3-kinase (PI3K/Akt) pathway proteins, cleaved caspase-3, Bad, Bcl-2, Bcl-xL, and Bax were determined using Western blot analyses. Tangeretin reduced the seizure scores and latency to first seizure of the rats and effectively activated the pilocarpine-induced suppression of PI3K/Akt signaling. Additionally, tangeretin effectively regulated the levels of apoptosis-inducing factor (AIF) in mitochondria as well as the expressions of apoptotic pathway proteins. Seizure-induced elevations in the activities and expressions of matrix metalloproteinases (MMPs)-2 and -9 were also modulated. The present results indicate that tangeretin exerted potent neuroprotective effects against pilocarpine-induced seizures via the activation of PI3K/Akt signaling and the regulation of MMPs. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.
The origin of the concept of partial epilepsy.
Eadie
1999-03-01
The International League Against Epilepsy has devised classifications which subdivide both epileptic seizures and the epilepsies and epileptic syndromes into two main types: generalized and partial. Epileptogenesis in the partial variety is believed to originate in a localized part of the cerebral cortex and results in clinical manifestations which appear to commence in only a restricted part of the sufferer's body. Use of the term 'partial' in relation to these entities has often been said to date back to James Cowles Prichard (1786-1849) who was the author of the second major work on epilepsy to be written in the UK. While Prichard certainly described 'partial epilepsy', he stated that he intended the words to refer to the fact that the disorder he described under that designation was only partly, and not fully, epileptic in nature. He did not refer to the fact that it affected only part of the body as his basis for using the term. In the absence of knowledge of localization of function in the cerebral cortex at Prichard's time of writing, he had no basis for deducing that the underlying epileptic process arose in only part of the brain. However, there is an earlier mention of the use of the word 'partial' in relation to epilepsy. This is to be found in the writings of the great Scottish physician William Cullen (1710-1790), and there is reason to believe that Prichard should have been aware of this. Cullen used 'partial' with an intention similar to the modern one, employing the word to refer to seizures which affected only part of the body. Credit for the origin of the idea of a 'partial' epilepsy should belong to Cullen; not only did he have priority over Prichard but his concept was closer to the modern one than was Prichard's. Copyright 1999 Harcourt Publishers Ltd.
The challenges that parents of children with epilepsy face: A qualitative study.
Kampra, Matina; Tzerakis, Nikolaos; Lund Holm Thomsen, Louise; Katsarou, Efstathia; Voudris, Konstantinos; D Mastroyianni, Sotiria; Mouskou, Stella; Drossou, Kyriaki S; Siatouni, Anna; Gatzonis, Stylianos
2017-06-01
This qualitative study explored the challenges that Greek parents/caregivers of children with controlled epilepsy (CwE) face regarding the disorder. Interviews were conducted based on open-ended questions guided by a review of the literature. A total of 91 parents/caregivers were recruited by neurologists at the neurology clinics of two Athens public hospitals. A hermeneutic phenomenological approach was used to explore parent/caregiver experiences. The data were grouped and analyzed through a textual interpretation. Two key challenges were identified for parents of CwE: the disclosure of epilepsy and the absence of adequate information about coping with epilepsy. Parents in Greece were hesitant to reveal their child's epilepsy to school staff and their wider social milieu. Also, although satisfied with the patient-centered approach they experienced with their hospital doctor, parents/caregivers found that they needed more education about the existing sources of psychosocial and emotional support to cope with their child's epilepsy personally and as a family. Finally, the parents/caregivers who let their child know about the epilepsy and discussed the implications with the child found that parent-child communication improved. This study provides valuable insight into the impact of epilepsy on parents of CwE, which might help hospital and school staff support families with greater understanding, sensitivity, and skill. The findings suggest that Greek authorities should staff hospitals and schools with experts and more systematically advertise sources of information about epilepsy and ways to cope with it. Copyright © 2017 Elsevier Inc. All rights reserved.
The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders
Spence, Sarah J; Schneider, Mark T
2009-01-01
Autism is a neurodevelopmental disorder of unknown etiology characterized by social and communication deficits and the presence of restricted interests/repetitive behaviors. Higher rates of epilepsy have long been reported, but prevalence estimates vary from as little as 5% to as much as 46%. This variation is probably the result of sample characteristics that increase epilepsy risk such as sample ascertainment, lower IQ, the inclusion of patients with non-idiopathic autism, age, and gender. However, critical review of the literature reveals that the rate in idiopathic cases with normal IQ is still significantly above the population risk suggesting that autism itself is associated with an increased risk of epilepsy. Recently there has been interest in the occurrence of epileptiform electroencephalograms (EEGs) even in the absence of epilepsy. Rates as high as 60% have been reported and some investigators propose that these abnormalities may play a causal role in the autism phenotype. While this phenomenon is still not well understood and risk factors have yet to be determined, the treatment implications are increasingly important. We review the recent literature to elucidate possible risk factors for both epilepsy and epileptiform EEGs. We then review existing data and discuss controversies surrounding treatment of EEG abnormalities. PMID:19454962
... Epilepsy Well Network The Managing Epilepsy Well (MEW) Network is a group of academic Prevention Research Centers that conduct studies related to epilepsy self-management. Read about MEW Network projects and how they are improving health and ...
Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy.
Liu, Bei; Niu, Le; Shen, Ming-Zhi; Gao, Lei; Wang, Chao; Li, Jie; Song, Li-Jia; Tao, Ye; Meng, Qiang; Yang, Qian-Li; Gao, Guo-Dong; Zhang, Hua
2014-10-01
Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under conditions of increased demand. Disruption of this astroglial-neuron metabolic coupling pathway may contribute to epileptogenesis. We measured MCT4 expression in temporal lobe epileptic foci excised from patients with intractable epilepsy and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients compared with controls, due at least partially to MCT4 promoter methylation. Expression of MCT4 also decreased progressively in pilocarpine-treated rats from 12 h to 14 days post-administration. Underexpression of MCT4 in cultured astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1) expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate.
Novel Frontiers in Epilepsy Treatments: Preventing Epileptogenesis by Targeting Inflammation
D'Ambrosio, Raimondo; Eastman, Clifford L.; Fattore, Cinzia; Perucca, Emilio
2014-01-01
Currently available epilepsy drugs only affect the symptoms (seizures), and there is a need for innovative treatments that target the underlying disease. Increasing evidence points to inflammation as a potentially important mechanism in epileptogenesis. In the last decade, a new generation of etiologically realistic syndrome-specific experimental models have been developed which are expected to capture the epileptogenic mechanisms operating in the corresponding patient populations, and to exhibit similar treatment-responsiveness. Recently, an intervention known have broad-ranging anti-inflammatory effects (selective brain cooling) has been found to prevent the development of spontaneously occurring seizures in an etiologically realistic rat model of post-traumatic epilepsy. Several drugs used clinically for other indications also have the potential for inhibiting inflammation, and should be investigated for anti-epileptogenic activity in these models. If results of such studies are positive, these compounds could enter rapidly Phase III trials in patients at high risk of developing epilepsy. PMID:23738999
Rood, Jennifer E; Schultz, Janet R; Rausch, Joseph R; Modi, Avani C
2014-10-01
The purpose of this study was to examine the following: 1) the course of perceived epilepsy-related stigma among children newly diagnosed with epilepsy (n=39) and their caregivers (n=97) over a two-year period, 2) the influence of seizure absence/presence on children and caregivers' perception of epilepsy-related stigma, and 3) the congruence of child and caregiver perception of child epilepsy-related stigma. Participants completed a measure of perceived epilepsy-related stigma at three time points, and seizure status was collected at the final time point. Results indicated that both caregivers (t(1,76)=-2.57, p<.01) and children with epilepsy (t(1,29)=-3.37, p<.01) reported decreasing epilepsy-related stigma from diagnosis to two years postdiagnosis. No significant differences were found in caregiver and child reports of perceived stigma for children experiencing seizures compared with children who have been seizure-free for the past year. Results revealed poor caregiver-child agreement of perceived epilepsy-related stigma at all three time points. These data suggest that while children with epilepsy initially perceive epilepsy-related stigma at diagnosis, their perception of stigma decreases over time. Having a better understanding of the course of epilepsy-related stigma provides clinicians with information regarding critical times to support families with stigma reduction interventions. Copyright © 2014 Elsevier Inc. All rights reserved.
Rood, Jennifer E.; Schultz, Janet R.; Rausch, Joseph R.; Modi, Avani C.
2014-01-01
The purpose of this study was to examine: 1) the course of perceived epilepsy-related stigma among children newly-diagnosed with epilepsy (n=39) and their caregivers (n=97) over a two year period, 2) the influence of seizure absence/presence on children and caregivers’ perception of epilepsy-related stigma, and 3) congruence of child and caregiver perception of child epilepsy-related stigma. Participants completed a measure of perceived epilepsy-related stigma at three time points, and seizure status was collected at the final time point. Results indicated both caregivers (t1,76 = − 2.57 p< .01) and children with epilepsy (t1,29=−3.37, p< .01) reported decreasing epilepsy-related stigma from diagnosis to two years post-diagnosis. No significant differences were found in caregiver and child report of perceived stigma for children experiencing seizures as compared to children who have been seizure-free for the past year. Results revealed poor caregiver-child agreement of perceived epilepsy-related stigma at all three time points. These data suggest that while children with epilepsy initially perceive epilepsy-related stigma at diagnosis, their perception of stigma decreases over time. Having a better understanding of the course of epilepsy-related stigma provides clinicians with information regarding critical times to support families with stigma reduction interventions. PMID:25173098
Interleukin-1β causes fluoxetine resistance in an animal model of epilepsy-associated depression.
Pineda, Eduardo A; Hensler, Julie G; Sankar, Raman; Shin, Don; Burke, Teresa F; Mazarati, Andréy M
2012-04-01
Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitary-adrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamo-pituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.
De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy.
de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah; Møller, Rikke S; Velinov, Milen; Dolzhanskaya, Natalia; Marsh, Eric; Helbig, Ingo; Devinsky, Orrin; Tang, Sha; Mefford, Heather C; Myers, Candace T; van Paesschen, Wim; Striano, Pasquale; van Gassen, Koen; van Kempen, Marjan; de Kovel, Carolien G F; Piard, Juliette; Minassian, Berge A; Nezarati, Marjan M; Pessoa, André; Jacquette, Aurelia; Maher, Bridget; Balestrini, Simona; Sisodiya, Sanjay; Warde, Marie Therese Abi; De St Martin, Anne; Chelly, Jamel; van 't Slot, Ruben; Van Maldergem, Lionel; Brilstra, Eva H; Koeleman, Bobby P C
2016-12-01
Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Kaur, Harpreet; Patro, Ishan; Tikoo, Kulbhushan; Sandhir, Rajat
2015-10-01
Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.
The concept of symptomatic epilepsy and the complexities of assigning cause in epilepsy.
Shorvon, Simon
2014-03-01
The concept of symptomatic epilepsy and the difficulties in assigning cause in epilepsy are described. A historical review is given, emphasizing aspects of the history which are relevant today. The historical review is divided into three approximately semicentenial periods (1860-1910, 1910-1960, 1960-present). A definition of symptomatic epilepsy and this is followed by listing of causes of symptomatic epilepsy. The fact that not all the causes of idiopathic epilepsy are genetic is discussed. A category of provoked epilepsy is proposed. The complexities in assigning cause include the following: the multifactorial nature of epilepsy, the distinction between remote and proximate causes, the role of nongenetic factors in idiopathic epilepsy, the role of investigation in determining the range of causes, the fact that not all symptomatic epilepsy is acquired, the nosological position of provoked epilepsy and the view of epilepsy as a process, and the differentiation of new-onset and established epilepsy. The newly proposed ILAE classification of epilepsy and its changes in terminologies and the difficulties in the concept of acute symptomatic epilepsy are discussed, including the inconsistencies and gray areas and the distinction between idiopathic, symptomatic, and provoked epilepsies. Points to be considered in future work are listed. Copyright © 2013 Elsevier Inc. All rights reserved.
Schmeiser, B; Hammen, T; Steinhoff, B J; Zentner, J; Schulze-Bonhage, A
2016-10-01
The intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. Our study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results were evaluated forming two groups: Group A consisted of isolated mesiotemporal lesions. Group B comprised patients with mTLE and additional focal cortical dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival analysis, using log-rank-tests and a multivariate regression model. Postoperative running down phenomenon was defined as seizure freedom after a period of gradual reduction of postoperative seizure frequency. This was compared to patients with ongoing epilepsy. Complete seizure freedom was achieved in 65.0% of investigated patients at 1year and in 56.5% at long-term follow-up of ≥5 years after surgery. Corresponding results were 64.2% and 56.8% at 1 and ≥5 years, respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive for favorable postoperative outcome in the total group were younger age at surgery, shorter duration of epilepsy, absence of secondarily generalized tonic-clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal epileptiform discharges (IEDs), complete resection of the lesion as well as absence of postoperative epileptiform activity and of early postoperative seizures. In subgroup analyses, patients of group A demonstrated longer postoperative seizure-free intervals with adolescent age at surgery, short duration of epilepsy before surgery and absence of SGTCS, whereas in
Quantifying interictal metabolic activity in human temporal lobe epilepsy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.
1990-09-01
The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on (18F)fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a singlemore » investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.« less
Ngoupaye, Gwladys Temkou; Bum, Elisabeth Ngo; Daniels, Willie Mark Uren
2013-10-20
In Cameroonian traditional medicine various extracts of Gladiolus dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that include headaches, digestive problems, muscle and joint aches, and some central nervous system disorders such as epilepsy, schizophrenia and mood disorders. Owning to this background, the aim of the study was to investigate whether an aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity focusing specifically on depression-like behaviours associated with epilepsy. We used the combined administration of atropine and pilocarpine to rats as our animal model of epilepsy. The forced swim test and spontaneous locomotor activity in the open field test were the two tools used to assess the presence of depression-like behaviour in epileptic and control animals. The following depression-related parameters were determined: plasma ACTH, plasma corticosterone, adrenal gland weight and hippocampal levels of brain-derived neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to that of fluoxetine. Our results showed that we had a valid animal model of epilepsy-induced depression as all 3 measures of construct, predictive and face validity were satisfied. The data indicated that Gladiolus dalenii significantly reduced the immobility times in the forced swim test and the locomotor activity as assessed in the open field. A similar pattern was observed when the HPA axis parameters were analysed. Gladiolus dalenii significantly reduced the levels of ACTH, corticosterone, but not the adrenal gland weight. Gladiolus dalenii significantly increased the level of BDNF in the hippocampus. In all parameters measured the effects of Gladiolus dalenii were significantly greater than those of fluoxetine. The results show that Gladiolus dalenii has antidepressant-like properties similar to those of fluoxetine in epilepsy-associated depressive states. The antidepressant activity of Gladiolus dalenii is
Ochoa-Gómez, Laura; López-Pisón, Javier; Lapresta Moros, Carlos; Fuertes Rodrigo, Cristina; Fernando Martínez, Ruth; Samper-Villagrasa, Pilar; Monge-Galindo, Lorena; Peña-Segura, José Luis; García-Jiménez, María Concepción
2017-01-01
A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Epilepsy Care in Ontario: An Economic Analysis of Increasing Access to Epilepsy Surgery
Bowen, James M.; Snead, O. Carter; Chandra, Kiran; Blackhouse, Gord; Goeree, Ron
2012-01-01
Background In August 2011 a proposed epilepsy care model was presented to the Ontario Health Technology Advisory Committee (OHTAC) by an Expert Panel on a Provincial Strategy for Epilepsy Care in Ontario. The Expert Panel recommended leveraging existing infrastructure in the province to provide enhanced capacity for epilepsy care. The point of entry for epilepsy care and the diagnostic evaluation for surgery candidacy and the epilepsy surgery would occur at regional and district epilepsy centres in London, Hamilton, Toronto, and Ottawa and at new centres recommended for northern and eastern Ontario. This economic analysis report was requested by OHTAC to provide information about the estimated budgetary impact on the Ontario health care system of increasing access to epilepsy surgery and to examine the cost-effectiveness of epilepsy surgery in both children and adults. Methods A prevalence-based “top-down” health care system budgetary impact model from the perspective of the Ministry of Health and Long-Term Care was developed to estimate the potential costs associated with expanding health care services to increase access to epilepsy care in general and epilepsy surgery in particular. A 5-year period (i.e., 2012–2016) was used to project annual costs associated with incremental epilepsy care services. Ontario Health Survey estimates of epilepsy prevalence, published epilepsy incidence data, and Canadian Census results for Ontario were used to approximate the number of individuals with epilepsy in the province. Applying these population estimates to data obtained from a recent field evaluation study that examined patterns of care and costs associated with epilepsy surgery in children, a health care system budget impact was calculated and the total costs and incremental costs associated with increasing access to surgery was estimated. In order to examine the cost-effectiveness of epilepsy surgery in children, a decision analysis compared epilepsy surgery to
Wu, Dong-Mei; Zhang, Yu-Tong; Lu, Jun; Zheng, Yuan-Lin
2018-09-01
This study aims to investigate the effect of microRNA-129 (miR-129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a normal group. Expression of miR-129, c-Fos, bax, and MAPK was detected by RT-qPCR and Western blotting. Hippocampal neurons were assigned into normal, blank, negative control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129 inhibitor+siRNA-c-Fos groups. The targeting relationship between miR-129 and c-Fos was predicted and verified by bioinformatics websites and dual-luciferase reporter gene assay. Cell proliferation after transfection was measured by MTT assay, and cell cycle and apoptosis by flow cytometry. c-Fos is a potential target gene of miR-129. Compared with the normal group, the other six groups showed a decreased miR-129 expression; increased expression of expression of c-Fos, Bax, and MAPK; decreased proliferation; accelerated apoptosis; more cells arrested in the G1 phase; and fewer cells arrested in the S phase. Compared with the blank and NC groups, the miR-129 mimic group and the siRNA-c-Fos group showed decreased expression of c-Fos, Bax, and MAPK, increased cells proliferation, and decreased cell apoptosis, fewer cells arrested in the G1 phase and more cells arrested in the S phase. However, the miR-129 inhibitor groups showed reverse consequences. This study suggests that miR-129 could inhibit the occurrence and development of epilepsy by repressing c-Fos expression through inhibiting the MAPK signaling pathway. © 2017 Wiley Periodicals, Inc.
Kellinghaus, Christoph; Lüders, Hans O
2004-12-01
Frontal lobe epilepsy accounts for only 10-20% of the patients in surgical series, but the incidence in non-surgical patient cohorts seems to be much higher. The typical clinical presentation of the seizures includes contralateral clonic movements, uni- or bilateral tonic motor activity as well as complex automatism. The yield of surface EEG may be limited due to the difficulty in detection of mesial or basal foci, and the patient may be misdiagnosed as having non-epileptic events. In addition, in patients with mesial frontal foci the epileptiform discharges may be mislateralized ("paradoxical lateralization"). Therefore, epilepsy surgery has been commonly considered as less promising in patients with frontal lobe epilepsy. However, the advent of sophisticated neuroimaging techniques, particularly MRI with epilepsy-specific sequences, has made it possible to delineate the epileptogenic lesion and detect a specific etiology, in an increasing number of patients. Thus, the success rate of epilepsy surgery in frontal lobe epilepsy is currently comparable to temporal lobe epilepsy, if the candidates are carefully selected. Patients with frontal lobe epilepsy who do not respond to anticonvulsive medication, and who are not eligible for epilepsy surgery may benefit from alternative approaches such as electrical brain stimulation.
Polack, Pierre-Olivier; Charpier, Stéphane
2006-01-01
Spontaneous high-voltage rhythmic spike (HVRS) discharges at 6–12 Hz have been widely described in the electrocorticogram (EcoG) of Long-Evans rats. These ECoG oscillations have been proposed to reflect a state of attentive immobility allowing the optimization of sensory integration within the corticothalamic pathway. This hypothesis has been challenged by recent studies emphasizing similarities between HVRS discharges and spike-and-wave discharges (SWDs) in well-established rat genetic models of absence epilepsy. Here, we made in vivo intracellular recordings to determine, for the first time, the cellular mechanisms responsible for the synchronized oscillations in the corticothalamic loop during HVRS discharges in the Long-Evans rats. We show that HVRS discharges are associated in corticothalamic neurones with rhythmic suprathreshold synaptic depolarizations superimposed on a tonic hyperpolarization, likely due to a process of synaptic disfacilitation. Simultaneously, thalamocortical neurones exhibit a large-amplitude ‘croissant’-shaped membrane hyperpolarization with a voltage sensitivity suggesting a potassium-dependent mechanism. This thalamic hyperpolarizing envelope was associated with a membrane oscillation resulting from interactions between excitatory synaptic inputs, a chloride-dependent inhibitory conductance and voltage-gated intrinsic currents. These cortical and thalamic cellular mechanisms underlying HVRS activity in Long-Evans rats are remarkably similar to those previously described in the thalamocortical networks during SWDs. Thus, the present study provides an additional support to the hypothesis that HVRS activity in Long-Evans rats is an absence-like seizure activity. PMID:16410284
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters ... may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, ...
Kommajosyula, Srinivasa P; Randall, Marcus E; Faingold, Carl L
2016-01-01
A major cause of mortality in epilepsy patients is sudden unexpected death in epilepsy (SUDEP). Post-ictal respiratory dysfunction following generalized convulsive seizures is most commonly observed in witnessed cases of human SUDEP. DBA mouse models of SUDEP are induced by audiogenic seizures (AGSz) and show high incidences of seizure-induced death due to respiratory depression. The relatively low incidence of human SUDEP suggests that it may be useful to examine seizure-associated death in an AGSz model that rarely exhibits sudden death, such as genetically epilepsy-prone rats (GEPR-9s). Adenosine is released extensively during seizures and depresses respiration, which may contribute to seizure-induced death. The present study examined the effects of inhibiting adenosine metabolism on the durations of post-ictal depression (PID) and respiratory distress (RD), changes in blood oxygen saturation (% SpO2), and the incidence of post-seizure mortality in GEPR-9s. Systemic administration of adenosine metabolism inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 30 mg/kg) with 5-Iodotubericidin (5-ITU, 3mg/kg) in GEPR-9s resulted in significant changes in the duration of AGSz-induced PID as compared to vehicle in both genders. These agents also significantly increased the duration of post-seizure RD and significantly decreased the mean% SpO2 after AGSz, as compared to vehicle but only in females. Subsequently, we observed that the incidences of death in both genders 12-48 h post-seizure were significantly greater in drug vs. vehicle treatment. The incidence of death in females was also significantly higher than in males, which is consistent with the elevated seizure sensitivity of female GEPR-9s developmentally. These results support a potentially important role of elevated adenosine levels following generalized seizures in the increased incidence of death in GEPR-9s induced by adenosine metabolism inhibitors. These findings may also be relevant to human SUDEP, in
Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy
Gelinas, Jennifer N.; Khodagholy, Dion; Thesen, Thomas; Devinsky, Orrin; Buzsáki, György
2016-01-01
Interactions between the hippocampus and cortex are critical for memory. Interictal epileptiform discharges (IEDs) identify epileptic brain regions and can impair memory, but how they interact with physiological patterns of network activity is mostly undefined. We show in a rat model of temporal lobe epilepsy that spontaneous hippocampal IEDs correlate with impaired memory consolidation and are precisely coordinated with spindle oscillations in the prefrontal cortex during NREM sleep. This coordination surpasses the normal physiological ripple-spindle coupling and is accompanied by decreased ripple occurrence. IEDs also induce spindles during REM sleep and wakefulness, behavioral states that do not naturally express these oscillations, by generating a cortical ‘DOWN’ state. We confirm a similar correlation of temporofrontal IEDs with spindles over anatomically restricted cortical regions in a pilot clinical examination of four subjects with focal epilepsy. These findings imply that IEDs may impair memory via misappropriation of physiological mechanisms for hippocampal-cortical coupling, suggesting a target to treat memory impairment in epilepsy. PMID:27111281
Dobriakova, Iu V; Tanaeva, K K; Dubynin, V A; Sarkisova, K Iu
2014-01-01
Maternal behavior in females of WAG/Rij and Wistar rats was compared in the place preference test from 2 to 8 days after delivery, as well as in the open field test from 4 to 6 days after delivery. In females of WAG/Rij rats compared with females of Wistar rats weaker expression of maternal motivation has been revealed in both tests: they spend less time in the compartment associated with pups. Moreover, in females of WAG/Rij rats, number of approaches to pups, number of pup-carryings and time spent with pups (time of contacts) were less than in females of Wistar rats. Reduced maternal motivation in females of WAG/Rij rats in the place preference test persisted in repeated testing, while in the open field test it was detected only in the first testing, indicating higher reliability of the place preference test for revealing inter-strain differences in the expression of maternal motivation. It is supposed that weaker expression of maternal behavior and preference is due to hypo-function of the mesolimbic dopaminergic bran system in WAG/Rij rats as a genetic model of depression associated with absence epilepsy.
Chen, B; Detyniecki, K; Choi, H; Hirsch, L; Katz, A; Legge, A; Wong, R; Jiang, A; Buchsbaum, R; Farooque, P
2017-05-01
The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy. We used logistic regression analysis to test the correlation between 83 non-AED/patient related potential predictor variables and the rate of PBSE. We then compared for each AED the rate of PBSEs and the rate of PBSEs that led to intolerability (IPBSE) while controlling for non-AED predictors of PBSEs. 922 patients (≤18 years old) were included in our study. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively. Overall, a history of psychiatric condition, absence seizures, intractable epilepsy, and frontal lobe epilepsy were significantly associated with increased PBSE rates. Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was significantly higher compared to other AEDs. LEV was also significantly associated with a high rate of IPBSEs (13.4%) and dose-decrease rates due to IPBSE (6.7%). Zonisamide (ZNS) was associated with significantly higher cessation rate due to IPBSE (9.1%) compared to other AEDs. Patients with a history of psychiatric condition, absence seizures, intractable epilepsy, or frontal lobe epilepsy are more likely to develop PBSE. PBSEs appear to occur more frequently in adolescent and children patients taking LEV compared to other AEDs. LEV-attributed PBSEs are more likely to be associated with intolerability and subsequent decrease in dose. The rate of ZNS-attributed IPBSEs is more likely to be associated with complete cessation of AED. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Devinsky, Orrin; Vezzani, Annamaria; O'Brien, Terence J; Jette, Nathalie; Scheffer, Ingrid E; de Curtis, Marco; Perucca, Piero
2018-05-03
Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences. Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies. In addition, one-third of patients will continue to have uncontrolled seizures. Epilepsy can substantially impair quality of life owing to seizures, comorbid mood and psychiatric disorders, cognitive deficits and adverse effects of medications. In addition, seizures can be fatal owing to direct effects on autonomic and arousal functions or owing to indirect effects such as drowning and other accidents. Deciphering the pathophysiology of epilepsy has advanced the understanding of the cellular and molecular events initiated by pathogenetic insults that transform normal circuits into epileptic circuits (epileptogenesis) and the mechanisms that generate seizures (ictogenesis). The discovery of >500 genes associated with epilepsy has led to new animal models, more precise diagnoses and, in some cases, targeted therapies.
Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats.
Hureaux, José; Lacoeuille, Franck; Lagarce, Frédéric; Rousselet, Marie-Christine; Contini, Aurélien; Saulnier, Patrick; Benoit, Jean-Pierre; Urban, Thierry
2017-01-01
Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf ® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.
Chronic inhibition of Ca(2+)/calmodulin kinase II activity in the pilocarpine model of epilepsy.
Churn, S B; Kochan, L D; DeLorenzo, R J
2000-09-01
The development of symptomatic epilepsy is a model of long-term plasticity changes in the central nervous system. The rat pilocarpine model of epilepsy was utilized to study persistent alterations in calcium/calmodulin-dependent kinase II (CaM kinase II) activity associated with epileptogenesis. CaM kinase II-dependent substrate phosphorylation and autophosphorylation were significantly inhibited for up to 6 weeks following epileptogenesis in both the cortex and hippocampus, but not in the cerebellum. The net decrease in CaM kinase II autophosphorylation and substrate phosphorylation was shown to be due to decreased kinase activity and not due to increased phosphatase activity. The inhibition in CaM kinase II activity and the development of epilepsy were blocked by pretreating seizure rats with MK-801 indicating that the long-lasting decrease in CaM kinase II activity was dependent on N-methyl-D-aspartate receptor activation. In addition, the inhibition of CaM kinase II activity was associated in time and regional localization with the development of spontaneous recurrent seizure activity. The decrease in enzyme activity was not attributed to a decrease in the alpha or beta kinase subunit protein expression level. Thus, the significant inhibition of the enzyme occurred without changes in kinase protein expression, suggesting a long-lasting, post-translational modification of the enzyme. This is the first published report of a persistent, post-translational alteration of CaM kinase II activity in a model of epilepsy characterized by spontaneous recurrent seizure activity.
Althaus, A L; Sagher, O; Parent, J M; Murphy, G G
2015-02-15
Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. Copyright © 2015 the American Physiological Society.
Optimization of epilepsy treatment with vagus nerve stimulation
NASA Astrophysics Data System (ADS)
Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges
2007-11-01
Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the
Benign childhood epilepsy with occipital paroxysms: neuropsychological findings.
Germanò, Eva; Gagliano, Antonella; Magazù, Angela; Sferro, Caterina; Calarese, Tiziana; Mannarino, Erminia; Calamoneri, Filippo
2005-05-01
Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory abilities (p<0.01), visual perception and visual-motor integration global abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01). The presence of cognitive dysfunctions in subjects with EBOS supports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other
Sabaz, M; Cairns, D R; Lawson, J A; Bleasel, A F; Bye, A M
2001-05-01
To determine whether refractory epilepsy affects the health-related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy. Subjects were parents of children with refractory epilepsy, whose syndrome had been defined using ILAE (International League Against Epilepsy) criteria and video-EEG monitoring. Children had the presence or absence of ID determined by formal neuropsychological or educational assessment. The relative effect of epilepsy on the two intellectual ability groups was determined using relevant clinical variables. Parents completed a valid epilepsy-specific HRQOL questionnaire for children, the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), and, depending on intellectual ability level, the Child Behaviour Checklist or Developmental Behaviour Checklist. Both intellectually normal children with epilepsy and children with epilepsy and ID were more likely to have psychosocial problems compared with their respective intellectual ability reference populations. The results also revealed that children with ID had reduced HRQOL compared with intellectually normal children; a result independent of epilepsy. Analysis of the relationship between epilepsy variables and HRQOL revealed that the QOLCE was the most sensitive in detecting variation in age at onset, seizure frequency, and medications taken. The HRQOL of children with refractory epilepsy is greatly affected, regardless of intellectual ability level. The presence of ID in children with epilepsy independently depresses HRQOL outcomes. Compared with two generic HRQOL measures, the QOLCE was the most sensitive measure to variation in epilepsy variables.
Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.
Lee, Cha Gon; Lee, Jeehun; Lee, Munhyang
2018-01-01
Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.
A Yassine, Imane; M Eldeeb, Waleed; A Gad, Khaled; A Ashour, Yossri; A Yassine, Inas; O Hosny, Ahmed
2018-07-01
Neurocognitive impairment represents one of the most common comorbidities occurring in children with idiopathic epilepsy. Diagnosis of the idiopathic form of epilepsy requires the absence of any macrostructural abnormality in the conventional MRI. Though changes can be seen at the microstructural level imaged using advanced techniques such as the Diffusion Tensor Imaging (DTI). The aim of this work is to study the correlation between the microstructural white matter DTI findings, the electroencephalographic changes and the cognitive dysfunction in children with active idiopathic epilepsy. A comparative cross-sectional study, included 60 children with epilepsy based on the Stanford-Binet 5th Edition Scores was conducted. Patients were equally assigned to normal cognitive function or cognitive dysfunction groups. The history of the epileptic condition was gathered via personal interviews. All patients underwent brain Electroencephalography (EEG) and DTI, which was analyzed using FSL. The Fractional Anisotropy (FA) was significantly higher whereas the Mean Diffusivity (MD) was significantly lower in the normal cognitive function group than in the cognitive dysfunction group. This altered microstructure was related to the degree of the cognitive performance of the studied children with epilepsy. The microstructural alterations of the neural fibers in children with epilepsy and cognitive dysfunction were significantly related to the younger age of onset of epilepsy, the poor control of the clinical seizures, and the use of multiple antiepileptic medications. Children with epilepsy and normal cognitive functions differ in white matter integrity, measured using DTI, compared with children with cognitive dysfunction. These changes have important cognitive consequences. Copyright © 2018 Elsevier Inc. All rights reserved.
Consciousness as a useful concept in epilepsy classification.
Blumenfeld, Hal; Meador, Kimford J
2014-08-01
Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms "dyscognitive" or "dialeptic" should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic-clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in
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Attitudes towards epilepsy among a sample of Turkish patients with epilepsy.
Yeni, Kubra; Tulek, Zeliha; Bebek, Nerses; Dede, Ozlem; Gurses, Candan; Baykan, Betul; Gokyigit, Aysen
2016-09-01
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. 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. 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. 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. Copyright © 2016 Elsevier Inc. All
Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report.
Khaing, Myo; Lim, Kheng-Seang; Tan, Chong-Tin
2014-09-01
We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.
Kids' perception about epilepsy.
Fernandes, Paula T; Cabral, Paula; Araújo, Ulisses; Noronha, Ana Lúcia A; Li, Li M
2005-06-01
Epilepsy remains a stigmatized condition. Lack of information has been pointed to as a cause of the perpetuation of stigma. Our goal was to survey children's perception of epilepsy. We used a questionnaire to determine if the children knew what epilepsy is and, if they did not know, what did they think epilepsy is. Twenty-nine children (15 girls; mean age 10 years, range 9-11 years) from a fourth-grade class of an elementary school in Campinas, Sao Paulo, Brazil, completed the questionnaires individually at the same time in the classroom. This took about 20 minutes. Only four children said they knew what epilepsy is: a disease of swallowing the tongue (3) and a disease that can kill (1). The perceptions of children who said they did not know what epilepsy is were: a disease that can kill, a disease of swallowing the tongue, a contagious disease, a serious illness, a head injury. Three children knew someone with epilepsy, and only two of them had said they knew what epilepsy is. The perceptions elicited from the children had a negative connotation; only one child mentioned a relationship between epilepsy and the brain. The spontaneous thoughts of children in this age group, without the contamination of political correctness, may reflect society's collective unconsciousness of the prejudice toward epilepsy and people with epilepsy and needs to be further investigated. Continuous, repetitive educational efforts are necessary in elementary school to change these negative perceptions of epilepsy in our society.
Bandstra, Nancy F; Camfield, Carol S; Camfield, Peter R
2008-09-01
Epilepsy directly affects 50 million people worldwide. Most can achieve excellent seizure control; however, people living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions and misunderstandings that have persisted for thousands of years. This paper reviews the frequency and nature of stigma toward epilepsy. Significant negative attitudes prevail in the adolescent and adult public worldwide leading to loneliness and social avoidance both in school and in the workplace. People with epilepsy are often wrongly viewed as having mental health and antisocial issues and as being potentially violent toward others. Twenty-five percent of adults having epilepsy describe social stigma as a result of their epilepsy. They fear rejection and often feel shame or loneliness from this diagnosis. The psychosocial and social impact of epilepsy is significant. Yet few specific interventions have been demonstrated to alter this perception. The effect on public education is primarily short-term, while change over the long-term in attitudes and inaccurate beliefs have not presently been proven effective. School education programming demonstrates improved knowledge and attitude a month after a classroom intervention, but persisting change over a longer period of time has not been evaluated. In-depth adult psycho-educational programs for adults with epilepsy improves knowledge, coping skills and level of felt stigma. However these gains have not demonstrated persistence over time. Myths, misconceptions and misunderstandings about epilepsy continue and programs aimed at increasing knowledge and reducing negative public attitudes should be enhanced.
The Managing Epilepsy Well Network:: Advancing Epilepsy Self-Management.
Sajatovic, Martha; Jobst, Barbara C; Shegog, Ross; Bamps, Yvan A; Begley, Charles E; Fraser, Robert T; Johnson, Erica K; Pandey, Dilip K; Quarells, Rakale C; Scal, Peter; Spruill, Tanya M; Thompson, Nancy J; Kobau, Rosemarie
2017-03-01
Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two
Hitiris, Nikolas; Mohanraj, Rajiv; Norrie, John; Brodie, Martin J
2007-05-01
All studies report an increased mortality risk for people with epilepsy compared with the general population. Population-based studies have demonstrated that the increased mortality is often related to the cause of the epilepsy. Common etiologies include neoplasia, cerebrovascular disease, and pneumonia. Deaths in selected cohorts, such as sudden unexpected death in epilepsy (SUDEP), status epilepticus (SE), suicides, and accidents are more frequently epilepsy-related. SUDEP is a particular cause for concern in younger people, and whether and when SUDEP should be discussed with patients with epilepsy remain problematic issues. Risk factors for SUDEP include generalized tonic-clonic seizures, increased seizure frequency, concomitant learning disability, and antiepileptic drug polypharmacy. The overall incidence of SE may be increasing, although case fatality rates remain constant. Mortality is frequently secondary to acute symptomatic disorders. Poor compliance with treatment in patients with epilepsy accounts for a small proportion of deaths from SE. The incidence of suicide is increased, particularly for individuals with epilepsy and comorbid psychiatric conditions. Late mortality figures in patients undergoing epilepsy surgery vary and are likely to reflect differences in case selection. Future studies of mortality should be prospective and follow agreed guidelines to better quantify risk and causation in individual populations.
Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies?
Noureldine, M H A; Harifi, G; Berjawi, A; Haydar, A A; Nader, M; Elnawar, R; Sweid, A; Al Saleh, J; Khamashta, M A; Uthman, I
2016-11-01
Epilepsy and seizures are reported among the neurological manifestations of antiphospholipid syndrome (APS) at a prevalence rate of approximately 8%, which is nearly 10 times the prevalence of epilepsy in the general population. The association of seizures with antiphospholipid antibodies (aPL) is even more significant in the presence of systemic lupus erythematosus (SLE). In this review, we discuss the epidemiological, pathophysiological, laboratory, clinical, and radiological aspects of this association, and derive suggestions on when to consider testing for aPL in epileptic patients and how to manage seizures secondary to APS based on literature data. Epilepsy due to APS should be considered in young patients presenting with seizures of unknown origin. Temporal lobe epilepsy seems to be particularly prevalent in APS patients. The pathogenesis is complex and may not only involve micro-thrombosis, but also a possible immune-mediated neuronal damage. Patients with seizures and positive aPL tend to develop thrombocytopenia and livedo racemosa more frequently compared with those without aPL. Magnetic resonance imaging (MRI) remains the imaging modality of choice in these patients. The presence of SLE and the presence of neurological symptoms significantly correlate with the presence of white matter changes on MRI. In contrast, the correlation between aPL positivity and the presence of white matter changes is very weak. Furthermore, MRI can be normal in more than 30-40% of neuropsychiatric lupus patients with or without aPL. aPL testing is recommended in young patients presenting with atypical seizures and multiple hyper-intensity lesions on brain MRI in the absence of other possible conditions. New MRI techniques can better understand the pathology of brain damage in neuro-APS. The therapeutic management of epileptic APS patients relies on anti-epileptic treatment and anticoagulant agents when there is evidence of a thrombotic event. In the absence of consensual
Martínez-Domínguez, Sara; Labrada-Abella, Jacob; Pedrós-Roselló, Alfonso; López-Gomáriz, Elena; Tenías-Burillo, José M
2013-06-16
The association of epilepsy with mental illness is described for years. Current is trying to relate certain epilepsies, such as juvenile myoclonic epilepsy (JME) with certain personality traits marked by emotional instability. We study a group of patients with JME and his mental state, with emphasis on the personality traits, presence of clinical anxiety or depression and quality of life, with other epilepsy patients versus a control group. Patients with epilepsy have more marked personality traits and symptoms of anxiety and depression, making a more negative assessment of their quality of life than the control group. Patients with others epilepsy have a higher other personality disorder and a poorer perception of their quality of life than patients with JME. Differences are obtained among patients with epilepsy and control groups in all the variables analyzed (personality, anxiety, depression and quality of life). JME patients have better scores on personality and quality of life than those in the other group of epilepsies.
Zhou, Zhike; Liu, Tingting; Sun, Xiaoyu; Mu, Xiaopeng; Zhu, Gang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng
2017-03-30
It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE. Copyright © 2017 Elsevier B.V. All rights reserved.
Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.
Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F
2010-11-01
Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be
Therapeutic Devices for Epilepsy
Fisher, Robert S.
2011-01-01
Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987
Epilepsy coexisting with depression.
Błaszczyk, Barbara; Czuczwar, Stanisław J
2016-10-01
Depression episodes in epilepsy is the most common commorbidity, affecting between 11% and 62% of patients with epilepsy. Although researchers have documented a strong association between epilepsy and psychiatric comorbidities, the nature of this relationship is poorly understood. The manifestation of depression in epilepsy is a complex issue having many interacting neurobiological and psychosocial determinants, including clinical features of epilepsy (seizure frequency, type, foci, or lateralization of foci) and neurochemical or iatrogenic mechanisms. Other risk factors are a family history of psychiatric illness, particularly depression, a lack of control over the seizures and iatrogenic causes (pharmacologic and surgical). In addition, treatment with antiepileptic drugs (AEDs) as well as social coping and adaptation skills have also been recognised as risk factors of depression associated with epilepsy. Epilepsy may foster the development of depression through being exposed to chronic stress. The uncertainty and unpredictability of seizures may instigate sadness, loneliness, despair, low self-esteem, and self-reproach in patients with epilepsy and lead to social isolation, stigmatization, or disability. Often, depression is viewed as a reaction to epilepsy's stigma and the associated poor quality of life. Moreover, patients with epilepsy display a 4-5 higher rate of depression and suicide compared with healthy population. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.
Epilepsy-related clinical factors and psychosocial functions in pediatric epilepsy.
Eom, Soyong; Eun, So-Hee; Kang, Hoon-Chul; Eun, Baik-Lin; Nam, Sang Ook; Kim, Sun Jun; Chung, Hee Jung; Kwon, Soon Hak; Lee, Young-Mock; Lee, Joon Soo; Kim, Dong Wook; Oh, Kyung Ja; Kim, Heung Dong
2014-08-01
The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy. Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records. Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects. Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.
Miller, Laurie A; Ricci, Monica; van Schalkwijk, Frank J; Mohamed, Armin; van der Werf, Ysbrand D
2016-06-01
Sleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence/absence of nocturnal discharges or presence/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Interictal mood and personality disorders in temporal lobe epilepsy and juvenile myoclonic epilepsy.
Perini, G I; Tosin, C; Carraro, C; Bernasconi, G; Canevini, M P; Canger, R; Pellegrini, A; Testa, G
1996-01-01
BACKGROUND: Mood disorders have been described as the commonest psychiatric disorders in patients with temporal lobe epilepsy. Secondary depression in temporal lobe epilepsy could be interpreted either as an adjustment reaction to a chronic disease or as a limbic dysfunction. To clarify this issue, a controlled study of psychiatric disorders was conducted in different forms of epileptic and non-epileptic chronic conditions. METHODS: Twenty outpatients with temporal lobe epilepsy, 18 outpatients with juvenile myoclonic epilepsy--a primary generalised seizure disorder--20 matched type I diabetic patients, and 20 matched normal controls were assessed by a structured interview (SADS) and by self rating scales (Beck depression inventory (BDI) and the state and trait anxiety scales STAIX1 and STAIX2). RESULTS: Sixteen (80%) patients with temporal lobe epilepsy fulfilled the criteria for a psychiatric diagnosis at the SADS interview with a significantly higher frequency than patients with juvenile myoclonic epilepsy (22%) and diabetic patients (10%) (P < 0.0001). The most frequent disorder in temporal lobe epilepsy was a mood disorder: 11 (55%) patients with temporal lobe epilepsy had depression compared with three patients with juvenile myoclonic epilepsy and two diabetic patients (P < 0.001). Eight patients with temporal lobe epilepsy with an affective disorder also had a comorbid personality or anxiety disorder. Patients with temporal lobe epilepsy scored significantly higher on BDI, STAIX1, and STAIX2 than the three control groups (P < 0.001, P < 0.01, P < 0.001). CONCLUSIONS: Patients with temporal lobe epilepsy have a higher incidence of affective and personality disorders, often in comorbidity, than patients with juvenile myoclonic epilepsy and diabetic patients suggesting that these psychiatric disorders are not an adjustment reaction to a chronic disease but rather reflect a limbic dysfunction. PMID:8971108
Will, Johanna L; Eckart, Moritz T; Rosenow, Felix; Bauer, Sebastian; Oertel, Wolfgang H; Schwarting, Rainer K W; Norwood, Braxton A
2013-06-15
The human serial reaction time task (SRTT) has widely been used to study the neural basis of implicit learning. It is well documented, in both human and animal studies, that striatal dopaminergic processes play a major role in this task. However, findings on the role of the hippocampus - which is mainly associated with declarative memory - in implicit learning and performance are less univocal. We used a SRTT to evaluate implicit learning and performance in rats with perforant pathway stimulation-induced hippocampal neuron loss; a clinically-relevant animal model of mesial temporal lobe epilepsy (MTLS-HS). As has been previously reported for the Sprague-Dawley strain, 8h of continuous stimulation in male Wistar rats reliably induced widespread neuron loss in areas CA3 and CA1 with a characteristic sparing of CA2 and the granule cells. Histological analysis revealed that hippocampal volume was reduced by an average of 44%. Despite this severe hippocampal injury, rats showed superior performance in our instrumental SRTT, namely shorter reaction times, and without a loss in accuracy, especially during the second half of our 16-days testing period. These results demonstrate that a hippocampal lesion can improve performance in a rat SRTT, which is probably due to enhanced instrumental performance. In line with our previous findings based on ibotenic-acid induced hippocampal lesion, these data support the hypothesis that loss or impairment of hippocampal function can enhance specific task performance, especially when it is dependent on procedural (striatum-dependent) mechanisms with minimal spatial requirements. As the animal model used here exhibits the defining characteristics of MTLE-HS, these findings may have implications for the study and management of patients with MTLE. Copyright © 2013 Elsevier B.V. All rights reserved.
Owczarek, K; Jędrzejczak, J
2013-01-01
Epileptic seizures have been known from time immemorial. Throughout the ages, however, ideas concerning the aetiology and treatment of epilepsy have changed considerably. Epilepsy is mentioned many times in the Pentateuch, where it is portrayed as a mysterious condition, whose symptoms, course and contingencies evade rational laws and explanations. In the Middle Ages, the accepted view which prevailed in social consciousness was that patients with epilepsy were possessed by Satan and other impure spirits. One common method of treatment of epileptic seizures was to submit the patient to cruel exorcisms. Patients were frequently injured in the process and some of them even died. Our understanding of epilepsy and its social consequences has improved considerably within the last century. The most significant progress as far as diagnosis and treatment of epilepsy is concerned took place in the last four decades of the twentieth century. Although we now know much more about epilepsy than we used to, this knowledge is still insufficiently popularized.
Ekenstedt, Kari J; Oberbauer, Anita M
2013-05-01
Epilepsy is the most common neurologic disease in dogs and many forms are considered to have a genetic basis. In contrast, some seizure disorders are also heritable, but are not technically defined as epilepsy. Investigation of true canine epilepsies has uncovered genetic associations in some cases, however, many remain unexplained. Gene mutations have been described for 2 forms of canine epilepsy: primary epilepsy (PE) and progressive myoclonic epilepsies. To date, 9 genes have been described to underlie progressive myoclonic epilepsies in several dog breeds. Investigations into genetic PE have been less successful, with only 1 causative gene described. Genetic testing as an aid to diagnosis, prognosis, and breeding decisions is available for these 10 forms. Additional studies utilizing genome-wide tools have identified PE loci of interest; however, specific genetic tests are not yet developed. Many studies of dog breeds with PE have failed to identify genes or loci of interest, suggesting that, similar to what is seen in many human genetic epilepsies, inheritance is likely complex, involving several or many genes, and reflective of environmental interactions. An individual dog's response to therapeutic intervention for epilepsy may also be genetically complex. Although the field of inherited epilepsy has faced challenges, particularly with PE, newer technologies contribute to further advances. © 2013 Elsevier Inc. All rights reserved.
[Current management of epilepsy].
Mizobuchi, Masahiro
2013-09-01
Epilepsy is one of the most common neurological disorders. Global neurological knowledge is essential for differential diagnosis of epileptic syndromes due to the diversity of ictal semiology, causes and syndromes. Neurologists play an important role in planning the medical care for patients with epilepsy, as medication is the most fundamental therapeutic strategy. Some patients with early-onset epilepsy require joint care by pediatric neurologists, those with intractable epilepsy by neurosurgeons, and those with psychological comorbidity by psychiatrists, and neurologists should play a coordinating role. While there is a great need for neurologists to participate in epilepsy care, neurologists in Japan currently do not participate substantially in the epilepsy management system. It is necessary to train more neurologists who can provide epilepsy care and conduct basic and clinical research on epilepsy by providing continuous education on epilepsy for general neurologists as well as pre- and post-graduate medical students. Most of the patients who require long-term treatment experience many medical problems and social handicaps, such as adverse effects of medication, social stigma, educational disadvantages and difficulties in obtaining driver's license. To improve the quality of life of patients with epilepsy, it is desirable to build broad medical-social networks participated by patients, doctors, neurological nurses, psychologists, social workers, school teachers, managers of employment support facilities and care givers.
[Epilepsy: incidens, prevalens and causes].
Forsgren, Lars; Sundelin, Heléne; Sveinsson, Olafur
2018-05-21
Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy.
Do Val-da Silva, Raquel A; Peixoto-Santos, Jose E; Kandratavicius, Ludmyla; De Ross, Jana B; Esteves, Ingrid; De Martinis, Bruno S; Alves, Marcela N R; Scandiuzzi, Renata C; Hallak, Jaime E C; Zuardi, Antonio W; Crippa, Jose A; Leite, Joao P
2017-01-01
The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa , in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5-4 Hz) and theta (4-10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders.
Do Val-da Silva, Raquel A.; Peixoto-Santos, Jose E.; Kandratavicius, Ludmyla; De Ross, Jana B.; Esteves, Ingrid; De Martinis, Bruno S.; Alves, Marcela N. R.; Scandiuzzi, Renata C.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Crippa, Jose A.; Leite, Joao P.
2017-01-01
The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders. PMID:28367124
Cognitive function in Nigerian children with newly diagnosed epilepsy: a preliminary report.
Lagunju, Ike Oluwa Abiola; Adeniyi, Yetunde Celia; Olukolade, Gbemi
2016-01-01
Epilepsy has long been associated with cognitive dysfunction and educational underachievement. The purpose of the study was to describe the baseline findings from a larger prospective study. New cases of epilepsy aged 6-16 years seen at a paediatric neurology clinic in Ibadan, Nigeria were evaluated for any evidence of cognitive impairment. Intelligence quotient (IQ) of the participants was measured using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). Scores on cognitive subtests and Full Scale IQ (FSIQ) were computed and association between the subsets scores and seizure variables were calculated. 40 children, 24 males and 16 females were studied and their ages ranged from 6 to 16 years with a mean of 10.8 (SD=3.0) years. Global intellectual functioning as measured by the WISC-IV was in the normal range (FSIQ scores <85) for 52.5% (n = 21) of the participants and the remaining participants (47.5%) scored between the borderline and severe category for intellectual disability. The strongest correlation was between 'caregiver's assessment of school performance' and FSIQ, (r = 0.70; p< 0.001). Age at onset of epilepsy and seizure type had no significant association with scores on the WISC-IV composite scores. There is a high prevalence of significant cognitive dysfunction in Nigerian children with epilepsy, even in the absence of any known brain insult. All children with epilepsy should have routine IQ assessment following diagnosis, in order to allow for early intervention when indicated, and thus, improved outcomes.
Post-epilepsy stroke: A review.
Jin, Jing; Chen, Rong; Xiao, Zheng
2016-01-01
Stroke and epilepsy are two of the most common neurological disorders and share a complicated relationship. It is well established that stroke is one of the most important causes of epilepsy, particularly new-onset epilepsy among the elderly. However, post-epilepsy stroke has been overlooked. In recent years, it has been demonstrated that epilepsy patients have increased risk and mortality from stroke when compared with the general population. Additionally, it was proposed that post-epilepsy stroke might be associated with antiepileptic drugs (AEDs), epileptic seizures and the lifestyle of epileptic patients. Here, we comprehensively review the epidemiology, causes and interventions for post-epilepsy stroke.
Sivakumar, Siddharth S.; Namath, Amalia G.; Tuxhorn, Ingrid E.; Lewis, Stephen J.
2016-01-01
We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy. PMID:26888110
Infections, inflammation and epilepsy
Vezzani, Annamaria; Fujinami, Robert S.; White, H. Steve; Preux, Pierre-Marie; Blümcke, Ingmar; Sander, Josemir W.; Löscher, Wolfgang
2016-01-01
Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled “epilepsy.” Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered. PMID:26423537
Canine epilepsy: an underutilized model.
Patterson, Edward E
2014-01-01
The mainstay of comparative research for epilepsy has been rodent models of induced epilepsy. This rodent basic science is essential, but it does not always translate to similar results in people, likely because induced epilepsy is not always similar enough to naturally occurring epilepsy. A good large animal, intermediate model would be very helpful to potentially bridge this translational gap. Epilepsy is the most common medical neurologic disease of dogs. It has been proposed since the 1970s that dogs with naturally occurring epilepsy could potentially be used as a comparative model for people of the underlying basis and therapy of epilepsy. There have been sporadic studies in the decades since then, with a relative surge in the last 10 years. These canine studies in the areas of genetics, drug therapy, dietary therapy, electroencelphalogram research, and devices for epilepsy show proof of concept that canine epilepsy can be a very good model for comparative research for many, but not all, facets of epilepsy. Results of research in canine epilepsy can and have benefited the improvement of treatment for both people and dogs. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Bhalla, Devender; Tchalla, Achille Edem; Marin, Benoît; Ngoungou, Edgard Brice; Tan, Chong Tin; Preux, Pierre-Marie
2014-09-01
Is epilepsy truly an "African ailment"? We aimed to determine this, since international health agencies often refer to epilepsy as an African disease and the scientific literature has spoken the same tone. Various published materials, mainly reports, articles, were used to gather Asian and African evidence on various aspects of epilepsy and many of its risk and associated factors. Our results suggest that in no way can epilepsy be considered as an African ailment and such characterization is most likely based on popular beliefs rather than scientific evidence. In comparison to Africa, Asia has a 5.0% greater burden from all diseases, and is 17.0% more affected from neuropsychiatric disorders (that include epilepsy). Given that more countries in Asia are transitioning, there may be large demographic and lifestyle changes in the near future. However these changes are nowhere close to those expected in Africa. Moreover, 23 million Asians have epilepsy in comparison to 3.3 million Africans and 1.2 million sub-Saharan Africans. In comparison to Africa, Asia has more untreated patients, 55.0% more additional epilepsy cases every year, because of its larger population, with greater treatment cost and possibly higher premature mortality. Of several associated factors discussed herein, many have more importance for Asia than Africa. The current state of epilepsy in Asia is far less than ideal and there is an urgent need to recognize and accept the importance of epilepsy in Asia. In no way can epilepsy be considered as an African ailment. This is most likely based on popular beliefs rather than scientific evidence. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
Epilepsy Care in the World: results of an ILAE/IBE/WHO Global Campaign Against Epilepsy survey.
Dua, Tarun; de Boer, Hanneke M; Prilipko, Leonid L; Saxena, Shekhar
2006-07-01
Information about existing resources available within the countries to tackle the huge medical, social, and economic burden caused by epilepsy is lacking. To fill this information gap, a survey of country resources available for epilepsy care was conducted within the framework of the ILAE/IBE/WHO Global Campaign Against Epilepsy. The study represents a major collaborative effort involving the World Health Organization (WHO), the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Data were collected from 160 countries representing 97.5% of the world population. The information included availability, role, and involvement of professional and patient associations for epilepsy, epilepsy treatment and services including antiepileptic drugs, human resources involved in epilepsy care, teaching in epileptology, disability benefits, and problems encountered by people with epilepsy and health professionals involved in epilepsy care. The data confirm that epilepsy care is grossly inadequate compared with the needs in most countries. In addition, large inequities exist across regions and income groups of countries, with low-income countries having extremely meager resources. Complete results of this survey can be found in the Atlas: Epilepsy Care in the World. The data reinforce the need for urgent, substantial, and systematic action to enhance resources for epilepsy care, especially in low-income countries.
Losartan prevents acquired epilepsy via TGF-β signaling suppression.
Bar-Klein, Guy; Cacheaux, Luisa P; Kamintsky, Lyn; Prager, Ofer; Weissberg, Itai; Schoknecht, Karl; Cheng, Paul; Kim, Soo Young; Wood, Lydia; Heinemann, Uwe; Kaufer, Daniela; Friedman, Alon
2014-06-01
Acquired epilepsy is frequently associated with structural lesions after trauma, stroke, and infections. Although seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor β (TGF-β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-β signaling and tested the efficacy of blocking the TGF-β pathway in preventing epilepsy. We addressed the role of TGF-β signaling in epileptogenesis in 2 different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, and magnetic resonance and direct optical imaging for blood-brain barrier permeability and vascular reactivity. Long-term electrocorticographic recordings were acquired in freely behaving animals. We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 pathway of TGF-β receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist, losartan, previously identified as a blocker of peripheral TGF-β signaling, effectively blocks albumin-induced TGF-β activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. TGF-β signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, a drug approved by the US Food and Drug Administration, as an efficient antiepileptogenic therapy for epilepsy associated with vascular injury. © 2014 American Neurological Association.
Losartan prevents acquired epilepsy via TGF-β signaling suppression
Bar-Klein, Guy; Cacheaux, Luisa P.; Kamintsky, Lyn; Prager, Ofer; Weissberg, Itai; Schoknecht, Karl; Cheng, Paul; Kim, Soo Young; Wood, Lydia; Heinemann, Uwe; Kaufer, Daniela; Friedman, Alon
2014-01-01
Objective Acquired epilepsy is frequently associated with structural lesions following trauma, stroke and infections. While seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor β (TGF-β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-β signaling and tested the efficacy of blocking the TGF-β pathway in preventing epilepsy. Methods We addressed the role of TGF-β signaling in epiletogenesis in two different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, magnetic resonance and direct optical imaging for blood-brain barrier (BBB) permeability and vascular reactivity. Long-term electrocorticographic (ECoG) recordings were acquired in freely behaving animals. Results We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 (ALK5) pathway of TGF-β receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist (AT1), losartan, previously identified as a blocker of peripheral TGF-β signaling, effectively blocks albumin-induced TGF-β activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation TGF-β signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, an FDA-approved drug, as an efficient anti-epileptogenic therapy for epilepsy associated with vascular injury. PMID:24659129
... abilities of people with epilepsy, fear seizures, or lack knowledge about seizure first aid or are not comfortable ... they help eliminate barriers to care, such as lack of transportation or ... both English- and Spanish-speaking adults with epilepsy. Researchers are ...
Epilepsy or seizures - discharge
... this page: //medlineplus.gov/ency/patientinstructions/000128.htm Epilepsy or seizures - discharge To use the sharing features on this page, please enable JavaScript. You have epilepsy . People with epilepsy have seizures. A seizure is ...
GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.
Koyama, Ryuta; Tao, Kentaro; Sasaki, Takuya; Ichikawa, Junya; Miyamoto, Daisuke; Muramatsu, Rieko; Matsuki, Norio; Ikegaya, Yuji
2012-08-01
Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABA(A) receptors (GABA(A)-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABA(A)-Rs caused a reversal in the direction of granule cell migration. This abnormal migration was prevented by RNAi-mediated knockdown of the Na(+)K(+)2Cl(-) co-transporter (NKCC1), which regulates the excitatory action of GABA. NKCC1 inhibition with bumetanide after febrile seizures rescued the granule cell ectopia, susceptibility to limbic seizures and development of epilepsy. Thus, this work identifies a previously unknown pathogenic role of excitatory GABA(A)-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures.
Tuft, Mia; Gjelsvik, Bergljot; Nakken, Karl O
2015-10-01
In "Epilepsy is Dancing", in Antony and the Johnsons' album "The Crying Light"(2009), the lyrics and accompanying music video depicts an epileptic seizure in which the person is transferred to another beautiful and magical world. This may be called "enchanted epilepsy"; i.e., the experience of epilepsy as deeply nourishing and (positively) transforming, is conveyed not only in the lyrics but also the visual and auditory qualities of the video. The seizure in the video gives associations to Shakespeare's "A Midsummer Night's dream". If epilepsy appears in music lyrics, the focus is mostly on negative aspects of the illness, such as horror, fear and repulsive sexuality associated with the fits [1,2]. Contradictory to these lyrics, Anthony and the Johnsons' song is an example of a positive portrayal of epilepsy. It is open to a multitude of meanings, emotional valence and appraisal of epilepsy. By widening the experiential range associated with epileptic seizures, these lyrics highlight the inherently construed nature of epileptic experience. The song stands out in several ways. First, it describes epilepsy in positive terms, prioritising the euphoric, ecstatic, potentially empowering and enhancing aspects of epileptic seizures. Second, the lyrics and accompanying video point to divine experiences associated with epileptic seizures. Through the lyrics and the music video we are, as an audience, able to sense a snicket of an epileptic seizure, but also the universal experience of loosing control. Copyright © 2015 Elsevier Inc. All rights reserved.
Rabies Tracing of Birthdated Dentate Granule Cells in Rat Temporal Lobe Epilepsy
Du, Xi; Zhang, Helen; Parent, Jack M.
2017-01-01
Objective To understand how monosynaptic inputs onto adult-born dentate granule cells (DGCs) are altered in experimental mesial temporal lobe epilepsy (mTLE) and whether their integration differs from early-born DGCs that are mature at the time of epileptogenesis. Methods A dual-virus tracing strategy combining retroviral birthdating with rabies virus-mediated putative retrograde trans-synaptic tracing was used to identify and compare presynaptic inputs onto adult- and early-born DGCs in the rat pilocarpine model of mTLE. Results Our results demonstrate that hilar ectopic DGCs preferentially synapse onto adult-born DGCs after pilocarpine-induced status epilepticus (SE) while normotopic DGCs synapse onto both adult- and early-born DGCs. We also find that parvalbumin+ and somatostatin+ interneuron inputs are greatly diminished onto early-born DGCs after SE. However, somatostatin+ interneuron inputs onto adult-born DGCs are maintained, likely due to preferential sprouting. Intriguingly, CA3 pyramidal cell backprojections that specifically target adult-born DGCs arise in the epileptic brain, while axons of interneurons and pyramidal cells in CA1 appear to sprout across the hippocampal fissure to preferentially synapse onto early-born DGCs. Interpretation These data support the presence of substantial hippocampal circuit remodeling after an epileptogenic insult that generates prominent excitatory monosynaptic inputs, both local recurrent and widespread feedback loops, involving DGCs. Both adult- and early-born DGCs are targets of new inputs from other DGCs as well as from CA3 and CA1 pyramidal cells after pilocarpine-treatment, changes that likely contribute to epileptogenesis in experimental mTLE. PMID:28470680
Pediatric epilepsy: The Indian experience
Gadgil, Pradnya; Udani, Vrajesh
2011-01-01
Epilepsy is a common clinical entity in neurology clinics. The understanding of the genetics of epilepsy has undergone a sea change prompting re-classification by the International league against epilepsy recently. The prevalence rates of epilepsy in India are similar to those of developed nations. However, the large treatment gap is a major challenge to our public health system. Perinatal injuries are a major causative factor in pediatric group. We have discussed a few common etiologies such as neurocysticercosis and newer genetic epilepsy syndromes. We have also briefly touched upon the Indian experience in pediatric epilepsy surgery. PMID:22069423
Pediatric epilepsy: The Indian experience.
Gadgil, Pradnya; Udani, Vrajesh
2011-10-01
Epilepsy is a common clinical entity in neurology clinics. The understanding of the genetics of epilepsy has undergone a sea change prompting re-classification by the International league against epilepsy recently. The prevalence rates of epilepsy in India are similar to those of developed nations. However, the large treatment gap is a major challenge to our public health system. Perinatal injuries are a major causative factor in pediatric group. We have discussed a few common etiologies such as neurocysticercosis and newer genetic epilepsy syndromes. We have also briefly touched upon the Indian experience in pediatric epilepsy surgery.
Barnes Heller, Heidi
2018-01-01
Seizures occur commonly in cats and can be classified as idiopathic epilepsy, structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid analysis as indicated. Antiepileptic drugs should be considered if a cat is having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital is often the drug of choice; however, levetiracetam may be more useful for certain types of epilepsy in cats. Long-term prognosis depends on the underlying diagnosis and response to therapy. Copyright © 2017 Elsevier Inc. All rights reserved.
Chung, Kenny; Liu, Yuan; Ivey, Susan L; Huang, Debbie; Chung, Corina; Guo, Wenting; Tseng, Winston; Ma, Daveena
2012-06-01
This study evaluated quality of life (QOL) in people with epilepsy (PWE) in the San Francisco Bay Area. This was a qualitative study examining QOL through the use of focus groups and of the QOLIE-31-P survey instrument. Six focus groups were conducted to examine self-reported challenges due to epilepsy. Focus groups were conducted for individuals who did and did not attend support groups. Individuals with epilepsy reported substantial difficulties with finances, physical and psychosocial functioning. Also, limited knowledge about services and relatively negative feelings toward self were common among newly diagnosed participants. Many of the issues surrounding QOL and challenges were shared across groups. Epilepsy-related social services appeared to be useful in helping PWE cope and in increasing PWE's awareness of key enabling services. Although many individuals with epilepsy reported poor QOL and other challenges, epilepsy-related services may be under-utilized due to a lack of awareness. Copyright © 2012 Elsevier Inc. All rights reserved.
Early deficits in spatial memory and theta rhythm in experimental temporal lobe epilepsy.
Chauvière, Laetitia; Rafrafi, Nadia; Thinus-Blanc, Catherine; Bartolomei, Fabrice; Esclapez, Monique; Bernard, Christophe
2009-04-29
Patients with temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, often display cognitive deficits. The time course and underlying mechanisms of cognitive decline remain unknown during epileptogenesis (the process leading to epilepsy). Using the rat pilocarpine model of TLE, we performed a longitudinal study to assess spatial and nonspatial cognitive performance during epileptogenesis. In parallel, we monitored interictal-like activity (ILA) in the hippocampal CA1 region, as well as theta oscillations, a brain rhythm central to numerous cognitive processes. Here, we report that spatial memory was altered soon after pilocarpine-induced status epilepticus, i.e., already during the seizure-free, latent period. Spatial deficits correlated with a decrease in the power of theta oscillations but not with the frequency of ILA. Spatial deficits persisted when animals had spontaneous seizures (chronic stage) without further modification. In contrast, nonspatial memory performances remained unaffected throughout. We conclude that the reorganization of hippocampal circuitry that immediately follows the initial insult can affect theta oscillation mechanisms, in turn, resulting in deficits in hippocampus-dependent memory tasks. These deficits may be dissociated from the process that leads to epilepsy itself but could instead constitute, as ILA, early markers in at-risk patients and/or provide beneficial therapeutic targets.
Holder, J Lloyd; Quach, Michael M
2016-10-01
The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability. 1 Individuals with loss-of-function mutations in SHANK3 have intellectual disability, autism, and variably, epilepsy. 2-5 The spectrum of seizure semiologies and electroencephalography (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately 2% of individuals with moderate to severe intellectual disabilities and 1% of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations. A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss-of-function mutation in SHANK3 identified through whole-exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset, and efficacy of therapy were determined. Electroencephalography studies were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist. There is a wide spectrum of seizure semiologies, frequencies, and severity in individuals with SHANK3 mutations. There are no specific EEG abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure. All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure, which can be challenging to identify due to comorbid intellectual disability in individuals with SHANK3 mutations; however, no consistent seizure semiology, neuroimaging
Computational models of epilepsy.
Stefanescu, Roxana A; Shivakeshavan, R G; Talathi, Sachin S
2012-12-01
Approximately 30% of epilepsy patients suffer from medically refractory epilepsy, in which seizures can not controlled by the use of anti-epileptic drugs (AEDs). Understanding the mechanisms underlying these forms of drug-resistant epileptic seizures and the development of alternative effective treatment strategies are fundamental challenges for modern epilepsy research. In this context, computational modeling has gained prominence as an important tool for tackling the complexity of the epileptic phenomenon. In this review article, we present a survey of computational models of epilepsy from the point of view that epilepsy is a dynamical brain disease that is primarily characterized by unprovoked spontaneous epileptic seizures. We introduce key concepts from the mathematical theory of dynamical systems, such as multi-stability and bifurcations, and explain how these concepts aid in our understanding of the brain mechanisms involved in the emergence of epileptic seizures. We present a literature survey of the different computational modeling approaches that are used in the study of epilepsy. Special emphasis is placed on highlighting the fine balance between the degree of model simplification and the extent of biological realism that modelers seek in order to address relevant questions. In this context, we discuss three specific examples from published literature, which exemplify different approaches used for developing computational models of epilepsy. We further explore the potential of recently developed optogenetics tools to provide novel avenue for seizure control. We conclude with a discussion on the utility of computational models for the development of new epilepsy treatment protocols. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Subependymal heterotopia: a distinct neuronal migration disorder associated with epilepsy.
Raymond, A A; Fish, D R; Stevens, J M; Sisodiya, S M; Alsanjari, N; Shorvon, S D
1994-01-01
Subependymal heterotopia has recently been recognised as a cause of epilepsy, but the clinical and investigational features have not been fully described. The clinical, psychometric, imaging, and electroencephalographic features of 13 adult patients with subependymal heterotopia and epilepsy have been reviewed. Age at seizure onset ranged from 18 months to 20 years (median 13 years). There were significantly more female (12) than male (1) patients (p < 0.01). Diagnosis of subependymal heterotopia was made by MRI in 11 patients and CT in two. The heterotopic grey matter was nodular in 11 patients and diffuse in two; bilateral in eight and unilateral in five. There were significantly more patients with predominant right than left cerebral hemisphere involvement (p < 0.01). The most commonly involved site was the occipital horn of the lateral ventricles (10 of 13 patients). Eleven patients presented with partial epilepsy, 10 of whom also had secondarily generalised seizures. The clinical description of the seizures often suggested either an occipital (four patients) or temporal (five patients) onset. Two patients presented with absence attacks without clear focal features. Patients demonstrated normal early milestones (12 of 13 patients), including normal motor development (all patients) and average or above average intelligence (10 of 13 patients). An EEG examination showed normal background activity in all but two patients, one of whom had large intracranial haematomas. Epileptiform activity was usually widespread (10 of 13 patients) and in three patients, there was generalised 3-Hz spike and wave activity that had previously led to an erroneous diagnosis of concomitant primary generalised epilepsy. Onset of epilepsy in the second decade of life, normal developmental milestones and intelligence, and the finding of an overwhelming female preponderance differentiates subependymal heterotopia from other cortical dysgeneses. The female preponderance supports the
Yang, Xiao-Yan; Long, Li-Li; Xiao, Bo
2016-07-01
To investigate the effects of temporal lobe epilepsy and idiopathic epilepsy on cognitive function and emotion in children and the risk factors for cognitive impairment. A retrospective analysis was performed for the clinical data of 38 children with temporal lobe epilepsy and 40 children with idiopathic epilepsy. The controls were 42 healthy children. All subjects received the following neuropsychological tests: Montreal Cognitive Assessment (MoCA) scale, verbal fluency test, digit span test, block design test, Social Anxiety Scale for Children (SASC), and Depression Self-rating Scale for Children (DSRSC). Compared with the control group, the temporal lobe epilepsy and idiopathic epilepsy groups showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). Compared with the idiopathic epilepsy group, the temporal lobe epilepsy group showed significantly lower scores of MoCA, verbal fluency, digit span, and block design (P<0.05) and significantly higher scores on SASC and DSRSC (P<0.05). In the temporal lobe epilepsy group, MoCA score was negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.571, -0.529, and -0.545 respectively; P<0.01). In the idiopathic epilepsy group, MoCA score was also negatively correlated with SASC score, DSRSC score, and seizure frequency (r=-0.542, -0.487, and -0.555 respectively; P<0.01). Children with temporal lobe epilepsy and idiopathic epilepsy show impaired whole cognition, verbal fluency, memory, and executive function and have anxiety and depression, which are more significant in children with temporal lobe epilepsy. High levels of anxiety, depression, and seizure frequency are risk factors for impaired cognitive function.
Management of refractory epilepsy.
Muñana, Karen R
2013-05-01
The term refractory epilepsy is utilized in veterinary medicine to describe a condition in which an animal with epilepsy fails to attain satisfactory seizure control or suffers intolerable side effects despite appropriate therapy with conventional antiepileptic drugs. Refractory epilepsy is an important problem in small animal practice as it occurs in approximately one-third of dogs with epilepsy. Consequently, there is much interest in identifying ways to more effectively treat this population of animals. More than a dozen new antiepileptic drugs have been approved for humans over the last 2 decades, and several of these drugs, including gabapentin, zonisamide, levetiracetam, and pregabalin, have been evaluated for the treatment of refractory seizures in veterinary patients. Nonmedical methods to treat poorly controlled epilepsy are also being explored. The 2 alternative forms of therapy that have shown the most promise in humans with epilepsy are electrical stimulation of the brain and dietary modification, both of which have also been evaluated in dogs. This overview summarizes the available data on pharmacologic as well as nonmedical treatment options for dogs and cats with refractory epilepsy. Although many forms of therapy are currently being utilized in clinical practice, our knowledge of the safety and efficacy of these treatments is limited. Additional randomized controlled trials are needed to better evaluate these novel therapies for refractory epilepsy in dogs and cats. © 2013 Elsevier Inc. All rights reserved.
Novel Rat Model for Neurocysticercosis Using Taenia solium
Verastegui, Manuela R.; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M.; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H.; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H.
2016-01-01
Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. PMID:26216286
Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy
Park, So Young; Kwon, Hye Eun; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Dong Seok; Kim, Heung Dong
2013-01-01
Background and Purpose: The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures. Methods: 48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children’s Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery. Results: Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children’s epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children’s improvement in cognitive and behavior issues. Conclusions: Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues. PMID:24649473
Segregation analysis of juvenile myoclonic epilepsy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weissbecker, K.A.; Delgado-Escueta, A.V.; Medina, M.T.
1994-09-01
Juvenile myoclonic epilepsy (JME) is a non-progressive epilepsy characterized by involuntary jerks and an adolescent age of onset. There conflicting reports regarding the mode of inheritance of JME - polygenic, autosomal recessive, and two-locus models have all been proposed. We performed a segregation analysis of 53 nuclear families of JME probands using the Elston and Stewart algorithm (S.A.G.E version 2.1). Relatives of the proband were classified as affected if they had a confirmed history of JME, absence or grand mal epilepsy, or if they were clinically asymptomatic but had 3.5-6 Hz multispike wave complexes on electroencephalography. Using these criteria, 40more » relatives were affected in addition to the 53 probands. All Mendelian models were rejected when compared to the unrestricted model which estimated transmission probabilities. The environmental models were also rejected. Of the Mendelian modes, the most parsimonious model was the autosomal recessive model with 53% penetrance and a rate of sporadic cases of 0.0039. We conclude that although there is evidence for a genetic component contributing to the familiality of JME, this component can not be explained by a single major gene. These results, along with contradictory reports regarding the linkage of JME to the short arm of chromosome 6, suggest the presence of genetic heterogeneity and/or a more complex mode of inheritance, such as a two-locus model. Since lod score linkage analyses are dependent on the assumption of a single major gene mode, these findings emphasize the necessity of performing non-parametric linkage analyses when studying JME.« less
Scharfman, Helen E.; Goodman, Jeffrey H.; Rigoulot, Marie-Aude; Berger, Russell E.; Walling, Susan G.; Mercurio, Thomas C.; Stormes, Kerry; Maclusky, Neil J.
2008-01-01
Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00–10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpine-induced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures. PMID:16084511
Opportunities for improving animal welfare in rodent models of epilepsy and seizures.
Lidster, Katie; Jefferys, John G; Blümcke, Ingmar; Crunelli, Vincenzo; Flecknell, Paul; Frenguelli, Bruno G; Gray, William P; Kaminski, Rafal; Pitkänen, Asla; Ragan, Ian; Shah, Mala; Simonato, Michele; Trevelyan, Andrew; Volk, Holger; Walker, Matthew; Yates, Neil; Prescott, Mark J
2016-02-15
Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
An explanation for sudden death in epilepsy (SUDEP).
Stewart, Mark
2018-03-14
This review traces the examination of autonomic, cardiovascular, and respiratory derangements associated with seizure activity in the clinical and preclinical literature generally, and in the author's animal model specifically, and concludes with the author's views on the potential mechanisms for sudden death in epilepsy (SUDEP). An animal model that employs kainic acid-induced seizures on a background of urethane anesthesia has permitted unprecedented access to the behavior of autonomic, cardiovascular, and respiratory systems during seizure activity. The result is a detailed description of the major causes of death and how this animal model can be used to develop and test preventative and interventional strategies. A critical translational step was taken when the rat data were shown to directly parallel data from definite SUDEP cases in the clinical literature. The reasons why ventricular fibrillation as a cause of death is so rarely reported and tools for verifying that seizure-associated laryngospasm can induce obstructive apnea as a cause of death are discussed in detail. Many details of the specific kinetics of activation of brainstem neurons serving autonomic and respiratory function remain to be elucidated, but the boundary conditions described in this review provide an excellent framework for more focused studies. A number of studies conducted in animal models of seizure activity and in epilepsy patients have contributed information on the autonomic, cardiovascular, and respiratory consequences of seizure activity spreading through hypothalamus and brainstem to the periphery. The result is detailed information on the systemic impact of seizure spread and the development of an understanding of the essential mechanistic features of sudden unexpected death in epilepsy (SUDEP). This review summarizes translation of data obtained from animal models to biomarkers that are useful in evaluating data from epilepsy patients.
Consciousness as a useful concept in epilepsy classification
Blumenfeld, Hal; Meador, Kimford J.
2014-01-01
Summary Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired
Stanley, David A.; Talathi, Sachin S.; Parekh, Mansi B.; Cordiner, Daniel J.; Zhou, Junli; Mareci, Thomas H.; Ditto, William L.
2013-01-01
For over a century epileptic seizures have been known to cluster at specific times of the day. Recent studies have suggested that the circadian regulatory system may become permanently altered in epilepsy, but little is known about how this affects neural activity and the daily pattern of seizures. To investigate, we tracked long-term changes in the rate of spontaneous hippocampal EEG spikes (SPKs) in a rat model of temporal lobe epilepsy. In healthy animals, SPKs oscillated with near 24-h period; however, after injury by status epilepticus, a persistent phase shift of ∼12 h emerged in animals that later went on to develop chronic spontaneous seizures. Additional measurements showed that global 24-h rhythms, including core body temperature and theta state transitions, did not phase shift. Instead, we hypothesized that locally impaired circadian input to the hippocampus might be responsible for the SPK phase shift. This was investigated with a biophysical computer model in which we showed that subtle changes in the relative strengths of circadian input could produce a phase shift in hippocampal neural activity. MRI provided evidence that the medial septum, a putative circadian relay center for the hippocampus, exhibits signs of damage and therefore could contribute to local circadian impairment. Our results suggest that balanced circadian input is critical to maintaining natural circadian phase in the hippocampus and that damage to circadian relay centers, such as the medial septum, may disrupt this balance. We conclude by discussing how abnormal circadian regulation may contribute to the daily rhythms of epileptic seizures and related cognitive dysfunction. PMID:23678009
Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.
Baulac, Michel; de Boer, Hanneke; Elger, Christian; Glynn, Mike; Kälviäinen, Reetta; Little, Ann; Mifsud, Janet; Perucca, Emilio; Pitkänen, Asla; Ryvlin, Philippe
2015-11-01
The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in
Halliday, Amy J; Campbell, Toni E; Razal, Joselito M; McLean, Karen J; Nelson, Timothy S; Cook, Mark J; Wallace, Gordon G
2012-02-01
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy. Copyright © 2011 Wiley Periodicals, Inc.
Epilepsy and vaccinations: Italian guidelines.
Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto
2013-10-01
Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Adherence to outpatient epilepsy quality indicators at a tertiary epilepsy center.
Pourdeyhimi, R; Wolf, B J; Simpson, A N; Martz, G U
2014-10-01
Quality indicators for the treatment of people with epilepsy were published in 2010. This is the first report of adherence to all measures in routine care of people with epilepsy at a level 4 comprehensive epilepsy center in the US. Two hundred patients with epilepsy were randomly selected from the clinics of our comprehensive epilepsy center, and all visits during 2011 were abstracted for documentation of adherence to the eight quality indicators. Alternative measures were constructed to evaluate failure of adherence. Detailed descriptions of all equations are provided. Objective measures (EEG, imaging) showed higher adherence than counseling measures (safety). Initial visits showed higher adherence. Variations in the interpretation of the quality measure result in different adherence values. Advanced practice providers and physicians had different adherence patterns. No patient-specific patterns of adherence were seen. This is the first report of adherence to all the epilepsy quality indicators for a sample of patients during routine care in a level 4 epilepsy center in the US. Overall adherence was similar to that previously reported on similar measures. Precise definitions of adherence equations are essential for accurate measurement. Complex measures result in lower adherence. Counseling measures showed low adherence, possibly highlighting a difference between practice and documentation. Adherence to the measures as written does not guarantee high quality care. The current quality indicators have value in the process of improving quality of care. Future approaches may be refined to eliminate complex measures and incorporate features linked to outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.
Adherence to outpatient epilepsy quality indicators at a tertiary epilepsy center
Pourdeyhimi, R.; Wolf, B.J.; Simpson, A.N.; Martz, G.U.
2014-01-01
Introduction Quality indicators for the treatment of people with epilepsy were published in 2010. This is the first report of adherence to all measures in routine care of people with epilepsy at a level 4 comprehensive epilepsy center in the US. Methods Two hundred patients with epilepsy were randomly selected from the clinics of our comprehensive epilepsy center, and all visits during 2011 were abstracted for documentation of adherence to the eight quality indicators. Alternative measures were constructed to evaluate failure of adherence. Detailed descriptions of all equations are provided. Results Objective measures (EEG, imaging) showed higher adherence than counseling measures (safety). Initial visits showed higher adherence. Variations in the interpretation of the quality measure result in different adherence values. Advanced practice providers and physicians had different adherence patterns. No patient-specific patterns of adherence were seen. Discussion This is the first report of adherence to all the epilepsy quality indicators for a sample of patients during routine care in a level 4 epilepsy center in the US. Overall adherence was similar to that previously reported on similar measures. Precise definitions of adherence equations are essential for accurate measurement. Complex measures result in lower adherence. Counseling measures showed low adherence, possibly highlighting a difference between practice and documentation. Adherence to the measures as written does not guarantee high quality care. Conclusion The current quality indicators have value in the process of improving quality of care. Future approaches may be refined to eliminate complex measures and incorporate features linked to outcomes. PMID:25171260
Thabit, Mohamed N; Sayed, Mohamed A; Ali, Magda M
2018-05-05
Epilepsy is a major public health problem worldwide. There are many misconceptions about people's knowledge and attitudes about epilepsy, which influence people's behavior towards patients with epilepsy. We conducted a cross-sectional study in Sohag University, a public Egyptian University, in Upper Egypt. We used an Arabic language designed questionnaire to assess people's knowledge about epilepsy and their attitudes towards patients with epilepsy. We included a total of 920 students in the study. 12.4% of study respondents had never heard of or read about epilepsy. Moreover, there was much misunderstanding about the etiology of epilepsy, as 68.2% of epileptic and 74.5% of nonepileptic respondents believe epilepsy is caused by evil spirits and evil eyes or due to psychiatric disorders. There were also many people who held negative attitudes towards patients with epilepsy in regards to major life milestones such as marriage and having children. Among nonepileptics, 54.5% believe epileptics should not marry and 49.9% believe they should not have children. Among patients with epilepsy, these percentages are 27.3% and 36.4% respectively. Knowledge about epilepsy is insufficient and should be increased. The attitudes towards patients with epilepsy are negative and should be changed in Upper Egypt. Copyright © 2018 Elsevier B.V. All rights reserved.
Gripper, Lucy B; Welburn, Susan C
2017-04-05
Neurocysticercosis (NCC) is a parasitic infection of the human central nervous system, the most common form of which involves infection of the brain parenchyma with the larval form of the Taenia solium tapeworm. A causal relationship between such an NCC infection and the development of epilepsy in infected individuals is acknowledged, in part supported by high levels of comorbidity in endemic countries worldwide. This study undertook a systematic review and critical analysis of the NCC-epilepsy relationship with the primary objective of quantifying the risk of developing epilepsy following NCC infection. A secondary aim was to analyse the proportions of NCC-associated epilepsy within different populations. Significant emphasis was placed on the importance of neuroimaging (CT or MRI) availability and use of clear guidelines for epilepsy diagnosis, in order to avoid overestimations of prevalence rates of either condition; a limitation identified in several previous studies. A common odds ratio of 2.76 was identified from meta-analysis of case-control studies, indicating that an individual infected with NCC has almost a three times higher risk of developing epilepsy than an uninfected individual. Furthermore, meta-analysis of studies identified a common proportion of 31.54% of epilepsy cases associated with NCC infection which suggests that amongst epileptic populations in at risk countries, approximately one-third may be associated with NCC infection. A significant finding was the lack of good clinical data to enable accurate determination of a causal relationship. Even studies that were included had noticeable limitations, including a general lack of consistency in diagnostics, and lack of accurate epidemiological data. This review highlights a need for consistency in research in this field. In the absence of reliable estimates of its global burden, NCC will remain of low priority in the eyes of funding agencies - a truly neglected disease.
Truccolo, Wilson; Wang, Jing; Nurmikko, Arto V.
2014-01-01
Transitions into primary generalized epileptic seizures occur abruptly and synchronously across the brain. Their potential triggers remain unknown. We used optogenetics to causally test the hypothesis that rhythmic population bursting of excitatory neurons in a local neocortical region can rapidly trigger absence seizures. Most previous studies have been purely correlational, and it remains unclear whether epileptiform events induced by rhythmic stimulation (e.g., sensory/electrical) mimic actual spontaneous seizures, especially regarding their spatiotemporal dynamics. In this study, we used a novel combination of intracortical optogenetic stimulation and microelectrode array recordings in freely moving WAG/Rij rats, a model of absence epilepsy with a cortical focus in the somatosensory cortex (SI). We report three main findings: 1) Brief rhythmic bursting, evoked by optical stimulation of neocortical excitatory neurons at frequencies around 10 Hz, induced seizures consisting of self-sustained spike-wave discharges (SWDs) for about 10% of stimulation trials. The probability of inducing seizures was frequency-dependent, reaching a maximum at 10 Hz. 2) Local field potential power before stimulation and response amplitudes during stimulation both predicted seizure induction, demonstrating a modulatory effect of brain states and neural excitation levels. 3) Evoked responses during stimulation propagated as cortical waves, likely reaching the cortical focus, which in turn generated self-sustained SWDs after stimulation was terminated. Importantly, SWDs during induced and spontaneous seizures propagated with the same spatiotemporal dynamics. Our findings demonstrate that local rhythmic bursting of excitatory neurons in neocortex at particular frequencies, under susceptible ongoing brain states, is sufficient to trigger primary generalized seizures with stereotypical spatiotemporal dynamics. PMID:25552645
Recent advances in epilepsy genetics.
Orsini, Alessandro; Zara, Federico; Striano, Pasquale
2018-02-22
In last few years there has been rapid increase in the knowledge of epilepsy genetics. Nowadays, it is estimated that genetic epilepsies include over than 30% of all epilepsy syndromes. Several genetic tests are now available for diagnostic purposes in clinical practice. In particular, next-generation sequencing has proven to be effective in revealing gene mutations causing epilepsies in up to a third of the patients. This has lead also to functional studies that have given insight into disease pathophysiology and consequently to the identification of potential therapeutic targets opening the way of precision medicine for epilepsy patients. This minireview is focused on the most recent advances in genetics of epilepsies. We will also overview the modern genomic technologies and illustrate the diagnostic pathways in patients with genetic epilepsies. Finally, the potential implications for a personalized treatment (precision medicine) are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.
Bruno, Elisa; Bartoloni, Alessandro; Sofia, Vito; Rafael, Florentina; Magnelli, Donata; Ortiz, Elio; Padilla, Sandra; Quattrocchi, Graziella; Bartalesi, Filippo; Segundo, Higinio; Zappia, Mario; Preux, Pierre-Marie; Nicoletti, Alessandra
2011-10-01
This study was performed to analyze sociocultural beliefs about epilepsy among Guaraní communities in Bolivia. People with epilepsy, their family members, the general population, and local health care personnel were interviewed about the meaning of and beliefs, feelings, and practices concerning epilepsy. Epilepsy is called mano-mano, a term that means being in a constant passage between life and death. The disease is attributed mainly to a failure to observe a fasting period and to other eating habits. Natural remedies are the most recommended treatments even though half of respondents reported that antiepileptic drugs may be effective. The concept of epilepsy as an embodied disease with natural causes appears to differ from that documented in other traditional societies. People with epilepsy do not represent a threat to the community, which seems to have an attitude aimed at their protection. Moreover, people from these communities appear to favor a combination of biomedical and traditional care systems. Copyright © 2011 Elsevier Inc. All rights reserved.
[Sleep disorders in epilepsy].
Kotova, O V; Akarachkova, E S
2014-01-01
The review of the literature on sleep disorders in epilepsy over the last two decades is presented. Paroxysmal phenomena of epileptic origin, nonepileptic paroxysms, antiepileptic drugs, polypragmasia and comorbid depression may affect sleep in epilepsy.Shortening of sleep time may cause seizures, hallucinations and depression because sleep plays an important role in the regulation of excitatory and inhibitory processes in the brain both in healthy people and in patients with epilepsy. According to the literature data, drugs (short treatment courses of hypnotics) or nonpharmacological methods should be used for treatment insomnia inpatients with epilepsy.
[Building epilepsy care network in Japan].
Otsuki, Taisuke
2012-01-01
Number of epilepsy patient in Japan officially surveyed by our government in 2008 is 219,000, which is only 0.17% of the total population and less than one third of the prevalence rate reported in Western countries. Number of epilepsy surgery per year in Japan is also low and less than half of other countries such as US, UK and Korea. These numbers may suggest that epilepsy care in Japan is not sufficient to cover all hidden medical needs of people with epilepsy at present. To solve this issue, our research group funded by the government have started to build an epilepsy care network among primary care physicians, secondary care neurology specialists and tertiary care epilepsy centers by utilizing a web site: Epilepsy Care Network-Japan (http://www.ecn-japan.com/) from July 2012. We are also proposing an epilepsy care algorithm suitable for our complex medical community consisted with various neurology specialists such as pediatric and adult neurologists, neurosurgeons and psychiatrists. Building Epilepsy Care Network in Japan may facilitate better medical and social support for people with epilepsy in Japan.
Pandya, Neil S; Vrbancic, Mirna; Ladino, Lady Diana; Téllez-Zenteno, José F
2013-01-01
Purpose We report the rare case of a patient with intractable epilepsy and escalating aggression, resulting in murder, who had complete resolution of her seizures and explosive behavior following a right temporal lobectomy. Patients and methods We searched the available literature from 1880 to 2013 for cases of epilepsy being used as a court defense for murder and collected information regarding the final sentencing outcomes. We selected 15 papers with a total of 50 homicides. Results We describe the case of a 47-year-old woman with drug-resistant right temporal epilepsy who developed increasing emotional lability, outbursts of anger and escalating violent behavior culminating in a violent murder. The patient was imprisoned while awaiting trial. In the interim, she underwent a successful temporal lobectomy with full resolution of seizures, interictal rage and aggressive behaviors. After the surgery, her charges were downgraded and she was transferred to a psychiatric facility. Conclusion The aggressive behavior associated with epilepsy has been described in the literature for over a century. A link between epilepsy and aggression has been disproportionally emphasized. These patients share some common characteristics: they are usually young men with a long history of epilepsy and lower than average intelligence. The violent act is postictal, sudden-onset, more likely to occur after a cluster of seizures and is usually related with alcohol abuse. PMID:23700367
ERIC Educational Resources Information Center
Brunquell, Phillip J.
1994-01-01
This paper discusses what epilepsy is and what it is not, defines types of epileptic seizures, identifies epilepsy syndromes, discusses antiepileptic drugs, describes seizure surgery, and examines issues of quality of life. (JDD)
Wirrell, Elaine C
2006-01-01
Only one prospective, controlled study has compared the risk of accidental injury in persons with epilepsy to controls without seizures. A mildly increased risk in the epilepsy group was found, predominantly due to injuries that result directly from a seizure. With regard to injury type, this study found significantly higher rates of only head and soft tissue injury; however, most injuries were minor. Several retrospective, population-based studies have suggested increased rates of more serious injury types. Submersion injury has a high mortality; the risk of submersion in children with epilepsy is 7.5-13.9 fold higher than in the general population. The risk of fracture is elevated approximately twofold, either resulting directly from seizure-induced injury or predisposed by drug-induced reduction in bone mineral density. Burns due to seizures account for between 1.6% and 3.7% of burn unit admissions. The risk of motor vehicle accidents in drivers with epilepsy also appears increased, albeit marginally. Several factors predispose to a higher risk of injury among those with epilepsy. Seizures resulting in falls increase the risk of concussion and other injuries. Higher seizure frequency, lack of a prolonged seizure-free interval, comorbid attention deficit disorder, or cognitive handicap may also increase the risk of injury. While some restrictions are necessary to protect the safety of the person with epilepsy, undue limitations may further limit achievement of independence. Given the high morbidity and mortality of submersion injury, those with active epilepsy should bathe or swim only with supervision; however, showering is a reasonable option. Appropriate vitamin D and calcium supplementation and periodic measurement of bone mineral density in those at risk for osteopenia are recommended.
Pennell, Page B.
2009-01-01
Synopsis The interactions between hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions which affect both men and women in various ways. Abnormalities of baseline endocrine status occur more commonly in people with epilepsy, and are most often described for the sex steroid hormone axis. Common symptoms include sexual dysfunction, decreased fertility, premature menopause, and polycystic ovarian syndrome. Antiepileptic drugs and hormones have a bidirectional interaction, with a decrease in the efficacy of hormonal contraceptive agents with some AEDs and a decrease in the concentration and efficacy of other AEDs with hormonal contraceptives. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy. However, this knowledge can be used to develop hormonal strategies to improve seizure control in people with epilepsy. PMID:19853217
Epilepsy treatment and creativity.
Zubkov, Sarah; Friedman, Daniel
2016-04-01
Creativity can be defined as the ability to understand, develop, and express, in a systematic fashion, novel orderly relationships. It is sometimes difficult to separate cognitive skills requisite for the creative process from the drive that generates unique new ideas and associations. Epilepsy itself may affect the creative process. The treatment of epilepsy and its comorbidities, by altering or disrupting the same neural networks through antiseizure drugs (ASDs), treatment of epilepsy comorbidities, ablative surgery, or neurostimulation may also affect creativity. In this review, we discuss the potential mechanisms by which treatment can influence the creative process and review the literature on the consequences of therapy on different aspects of creativity in people with epilepsy. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". Copyright © 2016 Elsevier Inc. All rights reserved.
Lee, Sang-Ahm; Choi, Eun-Ju; Jeon, Ji-Ye; Paek, Joon-Hyun
2017-09-01
The scriptural description of Jesus driving out an evil spirit from a boy with epilepsy supported the idea of the spiritual nature of epilepsy for centuries. Korea has a shorter history of Christianity than the Western world. We determined whether there are differences in attitudes toward epilepsy and perception of epilepsy-related stigma between people with and without belief in evangelical Christianity in Korea. Data were collected from evangelical churches and theological colleges. People without religious beliefs were enrolled as a control group through convenience sampling. The Public Attitudes Toward Epilepsy (PATE) scale and the modified Stigma Scale for epilepsy were used. Familiarity with and knowledge of epilepsy were also assessed. Evangelical Christians were categorized as professional or nonprofessional depending on whether they had received professional education in Christian theology. A total of 227 evangelical Christians and 139 controls were included. The scores on the Stigma Scale and in the two PATE domains were significantly lower in the professional Christian group than in the controls or the nonprofessional group (p<0.05) but did not differ between the nonprofessional group and controls. After controlling for confounders, only the professional group was independently associated with lower scores on the Stigma Scale and in the PATE personal domain (p<0.05). The remaining associations lost their significance. We found no differences in attitudes toward epilepsy and perception of stigma between people with and without belief in evangelical Christianity in Korea. Copyright © 2017 Elsevier Inc. All rights reserved.
Genetics Home Reference: juvenile myoclonic epilepsy
... Home Health Conditions Juvenile myoclonic epilepsy Juvenile myoclonic epilepsy Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). ...
Dissociative experiences in patients with epilepsy.
Özdemir, Osman; Cilingir, Vedat; Özdemir, Pınar Güzel; Milanlioglu, Aysel; Hamamci, Mehmet; Yilmaz, Ekrem
2016-03-01
A few studies have explored dissociative experiences in epilepsy patients. We investigated dissociative experiences in patients with epilepsy using the dissociative experiences scale (DES). Ninety-eight patients with epilepsy and sixty healthy controls were enrolled in this study. A sociodemographic questionnaire and the Dissociative Experiences Scale (DES), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered to the participants. The DES scores were significantly higher for the patients with epilepsy than the healthy individuals. The number of individuals with pathological dissociation (DES ≥ 30) was higher in the epilepsy group (n = 28) than in the control group (n = 8). Also, higher levels of dissociation were significantly associated with frequency of seizures, but were not associated with duration of epilepsy and age at onset of the disorder. These findings demonstrate that patients with epilepsy are more prone to dissociation than controls. The high rate of dissociative experiences among patients with epilepsy suggest that some epilepsy-related factors are present.
... Infants and Toddlers Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management ... De Quervain’s Tenosynovitis Home Family Health Pregnancy and Childbirth Epilepsy and Pregnancy Epilepsy and Pregnancy Share Print ...
Klein, Karl Martin; Pendziwiat, Manuela; Eilam, Anda; Gilad, Ronit; Blatt, Ilan; Rosenow, Felix; Kanaan, Moien; Helbig, Ingo; Afawi, Zaid
2017-07-01
Mutations or structural genomic alterations of the X-chromosomal gene ARHGEF9 have been described in male and female patients with intellectual disability. Hyperekplexia and epilepsy were observed to a variable degree, but incompletely described. Here, we expand the phenotypic spectrum of ARHGEF9 by describing a large Ethiopian-Jewish family with epilepsy and intellectual disability. The four affected male siblings, their unaffected parents and two unaffected female siblings were recruited and phenotyped. Parametric linkage analysis was performed using SNP microarrays. Variants from exome sequencing in two affected individuals were confirmed by Sanger sequencing. All affected male siblings had febrile seizures from age 2-3 years and intellectual disability. Three developed afebrile seizures between age 7-17 years. Three showed focal seizure semiology. None had hyperekplexia. A novel ARHGEF9 variant (c.967G>A, p.G323R, NM_015185.2) was hemizygous in all affected male siblings and heterozygous in the mother. This family reveals that the phenotypic spectrum of ARHGEF9 is broader than commonly assumed and includes febrile seizures and focal epilepsy with intellectual disability in the absence of hyperekplexia or other clinically distinguishing features. Our findings suggest that pathogenic variants in ARHGEF9 may be more common than previously assumed in patients with intellectual disability and mild epilepsy.
Wada, Kazumaru; Iwasa, Hiroto; Okada, Motohiro; Kawata, Yuko; Murakami, Takuya; Kamata, Akihisa; Zhu, Gang; Osanai, Takao; Kato, Takuhiko; Kaneko, Sunao
2004-01-01
We investigated the marital status of the patients with epilepsy to clarify the clinical factors impeding improvement of the quality of life in adults with epilepsy. We examined the marital status of adult patients with epilepsy who did not have mental retardation and had been treated at Hirosaki University Hospital, Hirosaki, Japan, for >5 years. The present study included 278 patients (142 men and 136 women) ranging from age 20 to 60 years. Sixty-six men and 52 women were single. Seventy-six males and 84 females had been married. The present study investigated the proportion of patients in whom seizures were controlled at the time of marriage. Percentages were only 30% for men and 22% for women. This result showed that in many patients, seizures were not controlled when they were married, which suggests that seizures themselves may not markedly inhibit marriage. Thirteen men and 16 women (total, 29 patients) had experienced divorce. Epilepsy was the cause of divorce in seven of the 29 patients who had been divorced. Of these seven patients, only one patient had informed the spouse of the disease before marriage. In the remaining six patients, seizures were witnessed after marriage or the disease was revealed by medication, which resulted in divorces. Concerning the association between marriage and the job, a close relation was found between the presence or absence of marriage and the presence or absence of a job among male patients.
Lo, Wan-Yu; Tsai, Fuu-Jen; Liu, Chung-Hsiang; Tang, Nou-Ying; Su, Shan-Yu; Lin, Shinn-Zong; Chen, Chun-Chung; Shyu, Woei-Cherng; Hsieh, Ching-Liang
2010-01-01
Uncaria rhynchophylla (Miq) Jack (UR) is a traditional Chinese herb and is used for the treatment of convulsive disorders, including epilepsy. Our previous study has shown that UR, as well as its major component rhynchophylline (RH), has an anticonvulsive effect and this effect is closely related to its scavenging activities of oxygen free radicals. The purpose of the present study was to investigate the effect of (UR) on the expression of proteins using a proteomics analysis in Sprague-Dawley (SD) rats with kainic acid (KA)-induced epileptic seizures. We profiled the differentially expressed proteins on two-dimensional electrophoresis (2-DE) maps derived from the frontal cortex and hippocampus of rat brain tissue 24 hours after KA-induced epileptic seizures. The results indicated that macrophage migration inhibitory factor (MIF) and cyclophilin A were under expressed in frontal cortex by an average of 0.19- and 0.23-fold, respectively. In the frontal cortex, MIF and cyclophilin A were significantly decreased in the KA group and these decreases were confirmed by the Western blots. However, in the hippocampus, only cyclophilin A was significantly decreased in the KA group. In addition, in real-time quantitative PCR (Q-PCR), MIF and cyclophilin A gene expressions were also significantly under expressed in the frontal cortex, and only the cyclophilin A gene was also significantly under expressed in the hippocampus in the KA group. These under expressions of MIF and cyclophilin A could be overcome by the treatment of UR and RH. In conclusion, the under expressions of MIF and cyclophilin A in the frontal cortex and hippocampus in KA-treated rats, which were overcome by both UR and UH treatment, suggesting that both MIF and cyclophilin A at least partly participate in the anticonvulsive effect of UR.
... brain. Devices to treat epilepsy include vagus nerve stimulation and responsive neurostimulation. Who Treats Epilepsy? A general ... Many men with epilepsy will experience changes in sexual drive and performance. For example, many men report ...
Insomnia in epilepsy is associated with continuing seizures and worse quality of life.
Quigg, Mark; Gharai, Sean; Ruland, Jeff; Schroeder, Catherine; Hodges, Matthew; Ingersoll, Karen S; Thorndike, Frances P; Yan, Guofen; Ritterband, Lee M
2016-05-01
To evaluate how insomnia is associated with seizure control and quality of life in patients with epilepsy. Consecutive patients with epilepsy attending clinical visits were surveyed with the Insomnia Severity Index (ISI). Patients had to be treated with at least one anticonvulsant and could not have had documented psychogenic pseudoseizure. The presence or absence of seizures and quality of life (QOLIE-P-10) within the past 4 weeks was recorded. Other variables included demographic and clinical data, sleep-wake timing, the Hörne-Östberg Morningness-Eveningness Questionnaire (MEQ), sleepiness (Epworth Sleepiness Scale (ESS), and mood (Center for Epidemiologic Studies Depression Scale, CES-D). 207 patients completed surveys. 43% had clinically significant insomnia, and 51% had at least mild insomnia. 58% were seizure free. Mean ISI scores were significantly worse for those with continuing seizures, and more severe ISI scores correlated strongly with worse QOL. Younger age, shorter duration of epilepsy, use of sedative/hypnotics, medical and sleep comorbidities, delayed sleep timing and chronotype, excessive sleepiness, and depression were all associated with more severe insomnia. Those with unexpected health care visits over the most recent 4 weeks had worse insomnia. After adjustment for these covariates, more severe insomnia remained significantly associated with lack of seizure freedom and with worse QOL. Insomnia is common in epilepsy, and is associated with short term poor seizure control and worse QOL. Future studies must evaluate cause-and-effect relationships. Assessment of insomnia may be important in the comprehensive care of epilepsy and may influence control of epileptic seizures. Copyright © 2016 Elsevier B.V. All rights reserved.
Control groups in paediatric epilepsy research: do first-degree cousins show familial effects?
Hanson, Melissa; Morrison, Blaise; Jones, Jana E; Jackson, Daren C; Almane, Dace; Seidenberg, Michael; Zhao, Qianqian; Rathouz, Paul J; Hermann, Bruce P
2017-03-01
To determine whether first-degree cousins of children with idiopathic focal and genetic generalized epilepsies show any association across measures of cognition, behaviour, and brain structure. The presence/absence of associations addresses the question of whether and to what extent first-degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of paediatric epilepsies. Participants were children (aged 8-18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment and brain imaging (cortical, subcortical, and cerebellar volumes), and parents completed the Child Behaviour Checklist (CBCL). Data (based on 42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioural, and imaging measures in a linear mixed model and case/control correlations were examined. Of the 42 uncorrected correlations involving cognitive, behavioural, and neuroimaging measures, only two were significant (p<0.05). The median correlation was 0.06. A test for whether the distribution of p values deviated from the null distribution under no association was not significant (p>0.25). Similar results held for the cognition/behaviour and brain imaging measures separately. Given the lack of association between cases and first-degree cousin performances on measures of cognition, behaviour, and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First-degree cousins appear to be unbiased controls for cognitive, behavioural, and neuroimaging research in paediatric epilepsy.
Shao, Yiye; Wang, Cuicui; Hong, Zhen; Chen, Yinghui
2016-03-01
It is widely recognized that P-glycoprotein (P-gp) mediates drug resistance in refractory epilepsy. However, the molecular mechanism underlying the up-regulation of P-gp expression remains unclear. Our previous studies have demonstrated that p38 mitogen-activated protein kinase (MAPK) regulates P-gp expression in cultured K562 cells. However, a lack of in vivo research leaves unanswered questions regarding whether p38MAPK regulates P-gp expression or drug resistance in refractory epilepsy. This in vivo study examined the effects of p38MAPK on the expression of P-gp and mdr1 in the rat brain and quantified antiepileptic drug (AED) concentrations in the hippocampal extracellular fluid. In addition, the role of p38MAPK in electrical and behavioral activity in a rat epilepsy model was studied. The results indicated that p38MAPK inhibition by SB202190 reduced P-gp expression, while increasing AED concentration in the hippocampal extracellular fluid in refractory epileptic rats. SB202190 also reduced the resistance to AEDs in drug-resistant rats and significantly reduced the severity of seizure activity. These results suggest that p38MAPK could participate in drug resistance in refractory epilepsy through the regulation of P-gp. We show that the specific inhibitor of p38MAPK could down-regulate the expression of multidrug transporter (P-glycoprotein) in blood-brain barrier, increase the concentration of antiepileptic drugs in the hippocampal extracellular fluid and reduce anti-epileptic drug resistance in refractory epileptic rats. We propose that the p38MAPK signaling pathway participates in drug resistance in refractory epilepsy through the regulation of P-glycoprotein expression. © 2015 International Society for Neurochemistry.
The social competence and behavioral problem substrate of new- and recent-onset childhood epilepsy.
Almane, Dace; Jones, Jana E; Jackson, Daren C; Seidenberg, Michael; Hermann, Bruce P
2014-02-01
This study examined patterns of syndrome-specific problems in behavior and competence in children with new- or recent-onset epilepsy compared with healthy controls. Research participants consisted of 205 children aged 8-18, including youth with recent-onset epilepsy (n=125, 64 localization-related epilepsy [LRE] and 61 idiopathic generalized epilepsy [IGE]) and healthy first-degree cousin controls (n=80). Parents completed the Child Behavior Checklist for children aged 6-18 (CBCL/6-18) from the Achenbach System of Empirically Based Assessment (ASEBA). Dependent variables included Total Competence, Total Problems, Total Internalizing, Total Externalizing, and Other Problems scales. Comparisons of children with LRE and IGE with healthy controls were examined followed by comparisons of healthy controls with those having specific epilepsy syndromes of LRE (BECTS, Frontal/Temporal Lobe, and Focal NOS) and IGE (Absence, Juvenile Myoclonic, and IGE NOS). Children with LRE and/or IGE differed significantly (p<0.05) from healthy controls, but did not differ from each other, across measures of behavior (Total Problems, Total Internalizing, Total Externalizing, and Other Problems including Thought and Attention Problems) or competence (Total Competence including School and Social). Similarly, children with specific syndromes of LRE and IGE differed significantly (p<0.05) from controls across measures of behavior (Total Problems, Total Internalizing, and Other Problems including Attention Problems) and competence (Total Competence including School). Only on the Thought Problems scale were there syndrome differences. In conclusion, children with recent-onset epilepsy present with significant behavioral problems and lower competence compared with controls, with little syndrome specificity whether defined broadly (LRE and IGE) or narrowly (specific syndromes of LRE and IGE). Copyright © 2013 Elsevier Inc. All rights reserved.
El Achkar, Christelle M; Spence, Sarah J
2015-06-01
The association between autism spectrum disorder (ASD) and epilepsy has been described for decades, and yet we still lack the full understanding of this relationship both clinically and at the pathophysiologic level. This review evaluates the available data in the literature pertaining to the clinical characteristics of patients with autism spectrum disorder who develop epilepsy and, conversely, patients with epilepsy who develop autism spectrum disorder. Many studies demonstrate an increased risk of epilepsy in individuals with ASD, but rates vary widely. This variability is likely secondary to the different study methods employed, including the study population and definitions of the disorders. Established risk factors for an increased risk of epilepsy in patients with ASD include intellectual disability and female gender. There is some evidence of an increased risk of epilepsy associated with other factors such as ASD etiology (syndromic), severity of autistic features, developmental regression, and family history. No one epilepsy syndrome or seizure type has been associated, although focal or localization-related seizures are often reported. The age at seizure onset can vary from infancy to adulthood with some evidence of a bimodal age distribution. The severity and intractability of epilepsy in populations with ASD have not been well studied, and there is very little investigation of the role that epilepsy plays in the autism behavioral phenotype. There is evidence of abnormal EEGs (especially epileptiform abnormalities) in children with ASD even in the absence of clinical seizures, but very little is known about this phenomenon and what it means. The development of autism spectrum disorder in patients with epilepsy is less well studied, but there is evidence that the ASD risk is greater in those with epilepsy than in the general population. One of the risk factors is intellectual disability, and there is some evidence that the presence of a particular seizure
Glycine Transporter 1 is a Target for the Treatment of Epilepsy
Shen, Hai-Ying; van Vliet, Erwin; Bright, Kerry-Ann; Hanthorn, Marissa; Lytle, Nikki; Gorter, Jan; Aronica, Eleonora; Boison, Detlev
2015-01-01
Glycine is the major inhibitory neurotransmitter in brainstem and spinal cord, whereas in hippocampus glycine exerts dual modulatory roles on strychnine-sensitive glycine receptors and on the strychnine-insensitive glycineB site of the N-methyl-D-aspartate receptor (NMDAR). In hippocampus, the synaptic availability of glycine is largely under control of glycine transporter 1 (GlyT1). Since epilepsy is a disorder of disrupted network homeostasis affecting the equilibrium of various neurotransmitters and neuromodulators, we hypothesized that changes in hippocampal GlyT1 expression and resulting disruption of glycine homeostasis might be implicated in the pathophysiology of epilepsy. Using two different rodent models of temporal lobe epilepsy (TLE) – the intrahippocampal kainic acid model of TLE in mice, and the rat model of tetanic stimulation-induced TLE – we first demonstrated robust overexpression of GlyT1 in the hippocampal formation, suggesting dysfunctional glycine signaling in epilepsy. Overexpression of GlyT1 in the hippocampal formation was corroborated in human TLE samples by quantitative real time PCR. In support of a role of dysfunctional glycine signaling in the pathophysiology of epilepsy, both the genetic deletion of GlyT1 in hippocampus and the GlyT1 inhibitor LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109. We conclude that GlyT1 overexpression in the epileptic brain constitutes a new target for therapeutic intervention, and that GlyT1 inhibitors constitute a new class of antiictogenic drugs. These findings are of translational value since GlyT1 inhibitors are already in clinical development to treat cognitive symptoms in schizophrenia. PMID:26302655
Seizure classification key to epilepsy management.
Davidson, Louise; Derry, Chris
2015-09-01
The diagnosis of epilepsy carries significant implications for physical, psychosocial and financial wellbeing as well as a small but significant increased risk of mortality. The diagnosis is often incorrect, potentially in up to 20% of cases, so should be revisited if seizures are not responding to treatment. Evidence indicates that misdiagnosis is significantly more common among nonspecialists. SIGN recommends that the diagnosis of epilepsy should be made by an epilepsy specialist, ideally in the setting of a dedicated first seizure or epilepsy clinic. An incorrect diagnosis of epilepsy can be harmful. There is an exhaustive list of epilepsy mimics that can result in misdiagnosis and expose patients to unnecessary treatment with antiepileptic drugs. Diagnosis relies primarily on the history. Investigations can support the diagnosis but cannot make it in isolation, and negative investigation findings are common in epilepsy. Brain imaging will be undertaken in most patients with epilepsy, but is not routinely required in those with a definite diagnosis of genetic generalised epilepsy. The EEG has limitations and can sometimes cloud rather than clarify the diagnostic picture. Distinguishing between a genetic generalised epilepsy and a focal epilepsy is vital as this influences investigation, treatment and prognosis. Generally medication should not be started following a single seizure except in specific circumstances or in cases where the risk of recurrence is high.
Lagunju, Ike Oluwa Abiola; Oyinlade, Alexander Opebiyi; Atalabi, Omolola Mojisola; Ogbole, Godwin; Tedimola, Olushola; Famosaya, Abimbola; Ogunniyi, Adesola; Ogunseyinde, Ayotunde Oluremi; Ragin, Ann
2015-01-01
Electroencephalography (EEG) remains the most important investigative modality in the diagnostic evaluation of individuals with epilepsy. Children living with epilepsy in the developing world are faced with challenges of lack of access to appropriate diagnostic evaluation and a high risk of misdiagnosis and inappropriate therapy. We appraised EEG studies in a cohort of Nigerian children with epilepsy seen in a tertiary center in order to evaluate access to and the impact of EEG in the diagnostic evaluation of the cases. Inter-ictal EEG was requested in all cases of pediatric epilepsy seen at the pediatric neurology clinic of the University College Hospital, Ibadan, Nigeria over a period of 18 months. Clinical diagnosis without EEG evaluation was compared with the final diagnosis post- EEG evaluation. A total of 329 EEGs were recorded in 329 children, aged 3 months to 16 years, median 61.0 months. Clinical evaluation pre-EEG classified 69.3% of the epilepsies as generalized. The a posteriori EEG evaluations showed a considerably higher proportion of localization-related epilepsies (33.6%). The final evaluation post EEG showed a 21% reduction in the proportion of cases labeled as generalized epilepsy and a 55% increase in cases of localization-related epilepsy(p<0.001). Here we show that there is a high risk of misdiagnosis and therefore the use of inappropriate therapies in children with epilepsy in the absence of EEG evaluation. The implications of our findings in the resource-poor country scenario are key for reducing the burden of care and cost of epilepsy treatment on both the caregivers and the already overloaded tertiary care services.
Hou, K-C; Chang, C-W; Chiou, J-C; Huang, Y-H; Shaw, F-Z
2011-12-01
This work presents a biomedical microsystem with a wireless radiofrequency (RF)-powered electronics and versatile sensors/actuators for use in nanomedicinal diagnosis and therapy. The cooling of brain tissue has the potential to reduce the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless power module with low-dropout linear regulator circuit convert RF signals into a DC voltage, can be implanted without a battery in monitoring free behaviour. A thermoelectric (TE) cooler is an actuator that is employed to cool down brain tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers are integrated to form module that is placed inside the head of a rat and fastened with a bio-compatible material. EEG signals are used to identify waveforms associated with epilepsy and are measured using readout circuits. The wireless part of the presented design achieves a low quiescent current and line/load regulation and high antenna/current efficiency with thermal protection to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the temperature to reduce the duration of this epileptic episode. Related characterisations demonstrate that the proposed design can be adopted in an effective nanomedicine microsystem.
Rosenow, Felix; Bast, Thomas; Czech, Thomas; Feucht, Martha; Hans, Volkmar H; Helmstaedter, Christoph; Huppertz, Hans-Jürgen; Noachtar, Soheyl; Oltmanns, Frank; Polster, Tilman; Seeck, Margitta; Trinka, Eugen; Wagner, Kathrin; Strzelczyk, Adam
2016-08-01
The definition of minimal standards remains pivotal as a basis for a high standard of care and as a basis for staff allocation or reimbursement. Only limited publications are available regarding the required staffing or methodologic expertise in epilepsy centers. The executive board of the working group (WG) on presurgical epilepsy diagnosis and operative epilepsy treatment published the first guidelines in 2000 for Austria, Germany, and Switzerland. In 2014, revised guidelines were published and the WG decided to publish an unaltered English translation in this report. Because epilepsy surgery is an elective procedure, quality standards are particularly high. As detailed in the first edition of these guidelines, quality control relates to seven different domains: (1) establishing centers with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuous medical education of employees, (4) surveillance by trained personnel during video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures, and (7) the cooperation of epilepsy centers. These standards required the certification of the different professions involved and minimum numbers of procedures. In the subsequent decade, quite a number of colleagues were certified by the trinational WG; therefore, the executive board of the WG decided in 2013 to make these standards obligatory. This revised version is particularly relevant given that the German procedure classification explicitly refers to the guidelines of the WG with regard to noninvasive/invasive preoperative video-EEG monitoring and invasive intraoperative diagnostics in epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Novel rat model for neurocysticercosis using Taenia solium.
Verastegui, Manuela R; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H
2015-08-01
Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Reexamining epilepsy-associated stigma: validation of the Stigma Scale of Epilepsy in Zambia.
Elafros, Melissa A; Bowles, Ryan P; Atadzhanov, Masharip; Mbewe, Edward; Haworth, Alan; Chomba, Elwyn; Birbeck, Gretchen L
2015-06-01
Epilepsy-associated stigma is an important patient-centered outcome, yet quantification remains challenging. Jacoby's 3-item Stigma Scale is commonly used to assess felt stigma among people with epilepsy (PWE) yet has ceiling effects. The Stigma Scale of Epilepsy (SSE) is a 24-item instrument that measures felt stigma among PWE and stigmatizing attitudes among others. If cross-culturally valid, the SSE may elucidate stigma determinants and provide an outcome measure for interventions. We assessed the properties of the SSE in 102 Zambian PWE using exploratory and confirmatory item response theories and compared the latent traits assessed by the SSE to those assessed by Jacoby's Stigma Scale. Differential item functioning based on forced disclosure of epilepsy was examined. The SSE yielded two latent traits--the first reflected difficulties faced by PWE; the second reflected emotions associated with epilepsy. Jacoby's Stigma Scale was associated only with the first latent trait. Forced disclosure was associated with "worry" and "pity" that were associated with the second latent trait. In Zambian PWE, the SSE captured two latent traits. One trait represents feelings associated with epilepsy, which is theorized as a substantial yet unmeasured part of stigma. The SSE performs well across cultures and may more comprehensively assess felt stigma than other instruments. Further validation is required to determine whether the SSE adequately assesses stigmatizing attitudes among people without epilepsy.
How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?
Yuen, Eunice S M; Sims, John R
2014-06-01
Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature. A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically. The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51). Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Multiplex families with epilepsy
Afawi, Zaid; Oliver, Karen L.; Kivity, Sara; Mazarib, Aziz; Blatt, Ilan; Neufeld, Miriam Y.; Helbig, Katherine L.; Goldberg-Stern, Hadassa; Misk, Adel J.; Straussberg, Rachel; Walid, Simri; Mahajnah, Muhammad; Lerman-Sagie, Tally; Ben-Zeev, Bruria; Kahana, Esther; Masalha, Rafik; Kramer, Uri; Ekstein, Dana; Shorer, Zamir; Wallace, Robyn H.; Mangelsdorf, Marie; MacPherson, James N.; Carvill, Gemma L.; Mefford, Heather C.; Jackson, Graeme D.; Scheffer, Ingrid E.; Bahlo, Melanie; Gecz, Jozef; Heron, Sarah E.; Corbett, Mark; Mulley, John C.; Dibbens, Leanne M.; Korczyn, Amos D.
2016-01-01
Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. PMID:26802095
Anastasopoulou, Stavroula; Kurth, Florian; Luders, Eileen; Savic, Ivanka
2017-01-01
The definition of two well-studied genetic generalized epilepsy syndromes (GGE) - juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCS) - suggests the absence of structural cerebral abnormalities. Nevertheless, there are various reports of such abnormalities (especially in JME), where effects mainly occur within thalamus and mesial prefrontal regions. This raises the question of whether JME is particularly linked to midline structure abnormalities, which may also involve the corpus callosum. We studied callosal morphology in a well-matched sample of 22 JME patients, 15 GTCS patients, and 42 controls (CTL) for all of whom we obtained T1-weighted data on a 3T MRI scanner. More specifically, we measured callosal thickness at 100 equidistant points across the callosal surface, and subsequently compared the three groups (JME, GTCS, and CTL) against each other. Significant differences between JME patients and controls were observed within the callosal genu, anterior midbody, and isthmus, with thinner regions in JME patients. There were no significant differences between GTCS patients and controls, and also not between JME patients and GTCS patients. The present outcomes point to callosal abnormalities in JME patients suggesting an impairment of interhemisperic communication between prefrontal, motor, parietal and temporal cortices. These findings further support the notion that structural aberrations are present and differentiated across GGE syndromes, with significant callosal deviations from normality in JME. Copyright © 2016 Elsevier B.V. All rights reserved.
Mitochondrial disorders and epilepsy.
Desguerre, I; Hully, M; Rio, M; Nabbout, R
2014-05-01
Mitochondrial respiratory chain defects (RCD) often exhibit multiorgan involvement, affecting mainly tissues with high-energy requirements such as the brain. Epilepsy is frequent during the evolution of mitochondrial disorders (30%) with different presentation in childhood and adulthood in term of type of epilepsy, of efficacy of treatment and also in term of prognosis. Mitochondrial disorders can begin at any age but the diseases with early onset during childhood have generally severe or fatal outcome in few years. Four age-related epileptic phenotypes could be identified in infancy: infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua and myoclonic epilepsy. Except for infantile spasms, epilepsy is difficult to control in most cases (95%). In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. Ketogenic diet could be an interesting alternative treatment in case of recurrent status epilepticus or pharmacoresistant epilepsy. Epileptic seizures increase the energy requirements of the metabolically already compromised neurons establishing a vicious cycle resulting in worsening energy failure and neuronal death. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Wagner, Ryan G; Newton, Charles R
2012-01-01
Both helminthiases and epilepsy occur globally, and are particularly prevalent in developing regions of the world. Studies have suggested an association between epilepsy and helminth infection, but a causal relationship is not established in many helminths, except perhaps with neurocysticercosis. We review the available literature on the global burden of helminths, and the epidemiological evidence linking helminths to epilepsy. We discuss possible routes that helminths affect the central nervous system of humans and the immunological response to helminth infection in the central nervous system, looking at possible mechanisms of epileptogenesis. Finally, we discuss the current gaps in knowledge about the interaction between helminths and epilepsy. PMID:19825109
Berendt, Mette; Farquhar, Robyn G; Mandigers, Paul J J; Pakozdy, Akos; Bhatti, Sofie F M; De Risio, Luisa; Fischer, Andrea; Long, Sam; Matiasek, Kaspar; Muñana, Karen; Patterson, Edward E; Penderis, Jacques; Platt, Simon; Podell, Michael; Potschka, Heidrun; Pumarola, Martí Batlle; Rusbridge, Clare; Stein, Veronika M; Tipold, Andrea; Volk, Holger A
2015-08-28
Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, "a common language", for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders.
Wong, Judy; Wirrell, Elaine
2006-03-01
To determine (a) whether children and teens with epilepsy participate in less physical activity and have higher body mass index (BMI) percentiles for age than do their siblings without epilepsy; and (b) what epilepsy-specific factors limit their participation. Patients 5-17 years, with a >or=3 month history of epilepsy, a development quotient >or=80, no major motor or sensory impairments, and at least one sibling without epilepsy in a similar age range, were identified from the Neurology Clinic database or at the time of clinic visit. Parents completed a questionnaire regarding sedentary activities and group, individual, and total sports activities. Children aged 11-15 years also completed the physical activity portion of the Health Behavior in School Aged Children questionnaire. Clinic charts were reviewed for seizure type, etiology, frequency, duration of epilepsy, and number of antiepileptic drugs (AEDs) ever taken. Teens with epilepsy participated in fewer group and total sports activities than did controls and were more likely to be potentially overweight or overweight. Receiving three or more AEDs in the past showed a significant negative correlation with sports participation. Although a trend was noted for those with higher seizure frequency to be less active, no other epilepsy-specific factors or prior seizures or seizure-related injury during a sports event correlated with participation in physical activity. Programs that promote exercise in adolescents with epilepsy should be encouraged to improve their physical, psychological, and social well-being.
The extratemporal lobe epilepsies in the epilepsy monitoring unit
Dash, Deepa; Tripathi, Manjari
2014-01-01
Extratemporal lobe epilepsies (ETLE) are characterized by the epileptogenic foci outside the temporal lobe. They have a wide spectrum of semiological presentation depending upon the site of origin. They can arise from frontal, parietal, occipital lobes and from hypothalamic hamartoma. We discuss in this review the semiology of different types of ETLE encountered in the epilepsy monitoring unit. PMID:24791090
Epilepsy Surgery: An Evidence Summary
2012-01-01
Background The Medical Advisory Secretariat, the predecessor of Health Quality Ontario, published an evidence-based analysis on functional brain imaging. This analysis highlighted the low uptake of epilepsy surgery in Ontario and internationally. Objective The objective of this analysis was to review the effectiveness of epilepsy surgery at reducing seizure frequency, as well as the safety of epilepsy surgery. Data Sources The literature search included studies published between January 1995 and March 2012. Search terms included epilepsy, surgery, resection, safety, and complications. Review Methods Studies were eligible for inclusion if they included at least 20 patients undergoing surgery; had a comparison group of patients with epilepsy who were not undergoing surgery; and reported follow-up periods of at least 1 year. Outcomes of interest included seizure frequency and complications associated with surgery. Results Six systematic reviews reported pooled seizure-free rates that ranged from 43% to 75%. Two randomized controlled trials compared the effectiveness of epilepsy surgery with no surgery in patients with drug-refractory epilepsy. Both trials reported significant improvements in the seizure frequency in the surgery group compared with the nonsurgery group. Eight retrospective cohort studies reported on the safety of epilepsy surgery. Of the 2,725 patients included in these studies, there were 3 deaths reportedly related to surgery. Other complications included hemiparesis, infection, and visual field defects. The studies had long follow-up periods ranging from a mean of 2 to 7 years. Limitations The most recent randomized controlled trial was stopped early due to slow enrolment rates. Thus results need to be interpreted with caution. Conclusions There is high quality evidence that epilepsy surgery is effective at reducing seizure frequency. Two randomized controlled trials compared surgery to no surgery in patients with drug-refractory epilepsy. Both
Holtkamp, Dominik; Opitz, Thoralf; Niespodziany, Isabelle; Wolff, Christian; Beck, Heinz
2017-01-01
In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage-gated sodium channels, and their potent activity in inhibiting high-frequency firing has been attributed to their strong use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels. The anticonvulsant drug lacosamide (LCM) also targets sodium channels, but has been shown to preferentially affect sodium channel slow inactivation processes, in contrast to most other anticonvulsants. We used whole-cell voltage clamp recordings in acutely isolated cells to investigate the effects of LCM on transient Na + currents. Furthermore, we used whole-cell current clamp recordings to assess effects on repetitive action potential firing in hippocampal slices. We show here that LCM exerts its effects primarily via shifting the slow inactivation voltage dependence to more hyperpolarized potentials in hippocampal dentate granule cells from control and epileptic rats, and from patients with epilepsy. It is important to note that this activity of LCM was maintained in chronic experimental and human epilepsy. Furthermore, we demonstrate that the efficacy of LCM in inhibiting high-frequency firing is undiminished in chronic experimental and human epilepsy. Taken together, these results show that LCM exhibits maintained efficacy in chronic epilepsy, in contrast to conventional use-dependent sodium channel blockers such as carbamazepine. They also establish that targeting slow inactivation may be a promising strategy for overcoming target mechanisms of pharmacoresistance. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Does arousal interfere with operant conditioning of spike-wave discharges in genetic epileptic rats?
Osterhagen, Lasse; Breteler, Marinus; van Luijtelaar, Gilles
2010-06-01
One of the ways in which brain computer interfaces can be used is neurofeedback (NF). Subjects use their brain activation to control an external device, and with this technique it is also possible to learn to control aspects of the brain activity by operant conditioning. Beneficial effects of NF training on seizure occurrence have been described in epileptic patients. Little research has been done about differentiating NF effectiveness by type of epilepsy, particularly, whether idiopathic generalized seizures are susceptible to NF. In this experiment, seizures that manifest themselves as spike-wave discharges (SWDs) in the EEG were reinforced during 10 sessions in 6 rats of the WAG/Rij strain, an animal model for absence epilepsy. EEG's were recorded before and after the training sessions. Reinforcing SWDs let to decreased SWD occurrences during training; however, the changes during training were not persistent in the post-training sessions. Because behavioural states are known to have an influence on the occurrence of SWDs, it is proposed that the reinforcement situation increased arousal which resulted in fewer SWDs. Additional tests supported this hypothesis. The outcomes have implications for the possibility to train SWDs with operant learning techniques. Copyright (c) 2010 Elsevier B.V. All rights reserved.
Ladino, Lady Diana; Hunter, Gary; Téllez-Zenteno, José Francisco
2013-10-01
The impact of health and disease has led many artists to depict these themes for thousands of years. Specifically, epilepsy has been the subject of many famous works, likely because of the dramatic and misunderstood nature of the clinical presentation. It often evokes religious and even mythical processes. Epilepsy surgical treatment has revolutionized the care of selected patients and is a relatively recent advance. Epilepsy surgery has been depicted in very few artistic works. The first portrait showing a potential surgical treatment for patients with epilepsy was painted in the 12th century. During the Renaissance, Bosch famously provided artistic commentary on traditional beliefs in "The stone of madness". Several of these works demonstrate a surgeon extracting a stone from a patient's head, at one time believed to be the source of all "folly", including epileptic seizures, psychosis, intellectual disability, depression, and a variety of other illnesses. There are some contemporary art pieces including themes around epilepsy surgery, all of them depicting ancient Inca Empire procedures such as trepanning. This article reviews the most relevant artistic works related with epilepsy surgery and also its historical context at the time the work was produced. We also present a painting from the Mexican artist Eduardo Urbano Merino that represents the patient's journey through refractory epilepsy, investigations, and ultimately recovery. Through this work, the artist intends to communicate hope and reassurance to patients going through this difficult process. © 2013.
Introduction-Pediatric epilepsy surgery techniques.
Rydenhag, Bertil; Cukiert, Arthur
2017-04-01
This supplement includes the proceedings from the Pediatric Epilepsy Surgery Techniques Meeting held in Gothenburg (July 4-5, 2014), which focused on presentations and discussions regarding specific surgical technical issues in pediatric epilepsy surgery. Pediatric epilepsy neurosurgeons from all over the world were present and active in very fruitful and live presentations and discussions. These articles represent a synopsis of the areas and subjects dealt with there. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Understanding of Epilepsy by Children and Young People with Epilepsy
ERIC Educational Resources Information Center
Lewis, Ann; Parsons, Sarah
2008-01-01
There is a striking dearth of studies focusing sensitively and in depth on the mainstream educational experiences of children with epilepsy, as viewed by those children themselves. The one-year project (2006-7) reported here addresses that gap. Children's perceptions about mainstream teachers' understanding of epilepsy and school-based needs are…
38 CFR 4.122 - Psychomotor epilepsy.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
38 CFR 4.122 - Psychomotor epilepsy.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
38 CFR 4.122 - Psychomotor epilepsy.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
38 CFR 4.122 - Psychomotor epilepsy.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
[Medical treatment of pediatric epilepsy].
Chiron, Catherine
2012-12-01
The aim of the medical treatment of childhood epilepsy is to control seizures as best as possible without any significant adverse event. Treatment includes classical and new antiepileptic drugs and ketogenic diet as well The drug(s) selected is dependent on the epilepsy syndrome: the same drug may completely control seizures in a given syndrome, but aggravate them in another one. Drug-drug interact ons must be taken into account when polytherapy is needed because doses need to be modified. The treatment of childhood epilepsy is different from that of adult epilepsy because many epilepsy syndromes are specifically paediatric and maturational process requires to prescribe these drugs according to age and weight.
Systemic penicillin as an experimental model of epilepsy.
Chen, R C; Huang, Y H; How, S W
1986-06-01
Systemic use of high-dose penicillin was studied in rats and cats to establish an experimental model of epilepsy. In rats, intraperitoneal injection of 2.5 to 5.0 million units/kg (MU/kg) penicillin was effective to induce spikes in 45.7 +/- 31.0 min (means +/- SD) and seizure in 71.5 +/- 38.4 min. In cats, intravenous administration of penicillin at 0.5 to 1.0 MU/kg induced spikes in 10.4 +/- 7.8 min and seizure in 32.2 +/- 19.8 min. Intraperitoneal use of penicillin at 1.0 to 2.0 MU/kg caused spikes in 24.0 +/- 18.4 min and seizure in 71.2 +/- 38.3 min. Pretreatment with intravenous isoniazid at 16.3 +/- 10.3 mg/kg significantly delayed the appearance of intravenous penicillin-induced spikes to 63.1 +/- 49.8 min or prevented the appearance of spikes and abolished the occurrence of seizures. Acupuncture at various points increased the penicillin-induced spikes and seizures.
Rational management of epilepsy.
Viswanathan, Venkataraman
2014-09-01
Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country.
Defining Incident Cases of Epilepsy in Administrative Data
Bakaki, Paul M.; Koroukian, Siran M.; Jackson, Leila W.; Albert, Jeffrey M.; Kaiboriboon, Kitti
2013-01-01
Purpose To determine the minimum enrollment duration for identifying incident cases of epilepsy in administrative data. Methods We performed a retrospective dynamic cohort study using Ohio Medicaid data from 1992–2006 to identify a total of 5,037 incident epilepsy cases who had at least 1 year of follow-up prior to epilepsy diagnosis (epilepsy-free interval). The incidence for epilepsy-free intervals from 1 to 8 years, overall and stratified by pre-existing disability status, was examined. The graphical approach between the slopes of incidence estimates and the epilepsy-free intervals was used to identify the minimum epilepsy-free interval that minimized misclassification of prevalent as incident epilepsy cases. Results As the length of epilepsy-free interval increased, the incidence rates decreased. A graphical plot showed that the decline in incidence of epilepsy became nearly flat beyond the third epilepsy-free interval. Conclusion The minimum of 3-year epilepsy-free interval is needed to differentiate incident from prevalent cases in administrative data. Shorter or longer epilepsy-free intervals could result in over- or under-estimation of epilepsy incidence. PMID:23791310
Niedzielska, Krystyna; Wolańczyk, Tomasz; Baker, Gus A; Jakoby, Ann; Doughty, Julie; De Boer, Hanneke
2004-01-01
The main aim of the European Study SPOKE (Sanofi-Synthelabo Programme for Outcome Knowledge of Epilepsy) designed by the Department of Neurosciences, Walton Hospital in Liverpool and the Centre for Health Services Research at the University of Newcastle upon Tyne, England, was to describe levels of knowledge about epilepsy among people with epilepsy and their families. It was equally important to identify gaps in understanding the most important aspects of the illness as well as to identify characteristics of people who score poorly on the Epilepsy Knowledge Questionnaire (EKQ). Another aim was to consider the implications of identified gaps in knowledge for future educational and psychosocial interventions. The study was conducted in 10 European countries and included 6156 people with epilepsy and 6506 members of their families. Results presented here relate to data for Poland only, where the examined population consisted of 1028 patients with epilepsy. 1033 questionnaires were returned by carers. Over 40% of all respondents had frequent seizures, and one third were seizure free. Scores on the Epilepsy Knowledge Questionnaire were high for the majority of respondents, but generally lower than in most of the countries. With reference to some aspects of illness important gaps in knowledge have been demonstrated. For example, it was shown that a significant number of respondents provided incorrect answers to questions relating to aspects of the etiology of epilepsy and administration of antiepileptic drug medication. There were a number of significant differences between the profiles of high and low scorers on the EKQ; high scorers were likely to have spent longer on education, have lower scores on the impact of epilepsy scale and report better adjustment to their epilepsy. The results of the study once again underline the importance of continued information among patients with epilepsy and their families in order to achieve.
Prolonged Febrile Seizures in the Immature Rat Model Enhance Hippocampal Excitability Long Term
Dube, Celine; Chen, Kang; Eghbal-Ahmadi, Mariam; Brunson, Kristen; Soltesz, Ivan; Baram, Tallie Z.
2011-01-01
Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. PMID:10716253
Mutations and Deletions in PCDH19 Account for Various Familial or Isolated Epilepsies in Females
Depienne, Christel; Trouillard, Oriane; Bouteiller, Delphine; Gourfinkel-An, Isabelle; Poirier, Karine; Rivier, François; Berquin, Patrick; Nabbout, Rima; Chaigne, Denys; Steschenko, Dominique; Gautier, Agnès; Hoffman-Zacharska, Dorota; Lannuzel, Annie; Lackmy-Port-Lis, Marilyn; Maurey, Hélène; Dusser, Anne; Bru, Marie; Gilbert-Dussardier, Brigitte; Roubertie, Agathe; Kaminska, Anna; Whalen, Sandra; Mignot, Cyril; Baulac, Stéphanie; Lesca, Gaetan; Arzimanoglou, Alexis; LeGuern, Eric
2011-01-01
Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation. © 2010 Wiley-Liss, Inc. PMID:21053371
[Epilepsy, cognition and ketogenic diet].
Garcia-Penas, J J
2018-03-01
Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.
Reexamining epilepsy-associated stigma: validation of the Stigma Scale of Epilepsy in Zambia
Bowles, Ryan P.; Atadzhanov, Masharip; Mbewe, Edward; Haworth, Alan; Chomba, Elwyn; Birbeck, Gretchen L.
2017-01-01
Purpose Epilepsy-associated stigma is an important patient-centered outcome, yet quantification remains challenging. Jacoby’s 3-item Stigma Scale is commonly used to assess felt stigma among people with epilepsy (PWE) yet has ceiling effects. The Stigma Scale of Epilepsy (SSE) is a 24-item instrument that measures felt stigma among PWE and stigmatizing attitudes among others. If cross-culturally valid, the SSE may elucidate stigma determinants and provide an outcome measure for interventions. Methods We assessed the properties of the SSE in 102 Zambian PWE using exploratory and confirmatory item response theories and compared the latent traits assessed by the SSE to those assessed by Jacoby’s Stigma Scale. Differential item functioning based on forced disclosure of epilepsy was examined. Results The SSE yielded two latent traits—the first reflected difficulties faced by PWE; the second reflected emotions associated with epilepsy. Jacoby’s Stigma Scale was associated only with the first latent trait. Forced disclosure was associated with “worry” and “pity” that were associated with the second latent trait. Conclusions In Zambian PWE, the SSE captured two latent traits. One trait represents feelings associated with epilepsy, which is theorized as a substantial yet unmeasured part of stigma. The SSE performs well across cultures and may more comprehensively assess felt stigma than other instruments. Further validation is required to determine whether the SSE adequately assesses stigmatizing attitudes among people without epilepsy. PMID:25416086
Sarkisova, Karine Yu; Fedotova, Irina B; Surina, Natalia M; Nikolaev, Georgy M; Perepelkina, Olga V; Kostina, Zoya A; Poletaeva, Inga I
2017-03-01
Anxiety and depression are the most frequent comorbidities of different types of convulsive and non-convulsive epilepsies. Increased anxiety and depression-like phenotype have been described in the genetic absence epilepsy models as well as in models of limbic epilepsy and acquired seizure models, suggesting a neurobiological connection. However, whether anxiety and/or depression are comorbid to audiogenic epilepsy remains unclear. The aim of this study was to investigate whether anxiety or depression-like behavior can be found in rat strains with different susceptibility to audiogenic seizures (AS) and whether chronic fluoxetine treatment affects this co-morbidity. Behavior in the elevated plus-maze and the forced swimming test was studied in four strains: Wistar rats non-susceptible to AS; Krushinsky-Molodkina (KM) strain, selectively bred for AS propensity from outbred Wistar rats; and a selection lines bred for maximal AS expression (strain "4") and for a lack of AS (strain "0") from KM×Wistar F2 hybrids. Effects of chronic antidepressant treatment on AS and behavior were also evaluated. Anxiety and depression levels were higher in KM rats (with AS) compared with Wistar rats (without AS), indicating the comorbidity with AS. However, in strains "4" and "0" with contrasting AS expression, but with a genetic background close to KM rats, anxiety and depression were not as divergent as in KMs versus Wistars. Fluoxetine treatment exerted an antidepressant effect in all rat strains irrespective of its effect on AS. Genetic background contributes substantively to the co-morbidity of anxiety and depression with AS propensity. Copyright © 2016 Elsevier Inc. All rights reserved.
Fauser, S; Soellner, C; Bien, C G; Tumani, H
2017-09-01
To compare the frequency of intrathecal immunoglobulin (Ig) synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic'). Patients with epileptic (n = 301) and non-epileptic (n = 10) seizures were retrospectively screened for autochthonous intrathecal Ig synthesis and oligoclonal bands (OCBs) in the cerebrospinal fluid. Intrathecal IgG/OCBs were detected in 8% of patients with epilepsies of unknown etiology, 5% of patients with first seizures of unknown cause and 0-4% of patients with epilepsy due to brain tumors, cerebrovascular disease or other etiologies. Intrathecal IgG/OCBs were not seen in patients with psychogenic seizures. Identical OCBs in serum and cerebrospinal fluid were more common in all patient groups (10-40% depending on underlying etiology). Intrathecal IgG synthesis/OCBs were observed slightly more frequently in patients with 'cryptogenic' epilepsy and with first seizures of unknown etiology than in other patient groups. However, this remained an infrequent finding and thus we could not confirm humoral immunity as a leading disease mechanism in patients with epilepsy in general or with unknown etiology in particular. © 2017 EAN.
Epilepsy, cognition and behavior.
Gulati, Sheffali; Yoganathan, Sangeetha; Chakrabarty, Biswaroop
2014-10-01
Epilepsy is defined as two or more unprovoked seizures. Epileptic patients have intellectual disability and behavioral co-morbidities to the tune of up to 25 and 75% respectively. Various factors like underlying etiology, socioeconomic environment at home, age at onset, seizure semiology, seizure descriptors like duration, severity and frequency, therapy related adverse effects secondary to antiepileptic drugs and epilepsy surgery have been implicated for the causation of cognitive and behavioral impairment in epilepsy. Cognitive epilepsy has emerged as a specific entity. This may manifest as a transient behavioral or cognitive change, insidous onset subacute to chronic encephalopathy or more catastrophic in the form of nonconvulsive status epilepticus. Cognitive impairment seen in epileptic children include difficulties in learning, memory, problem solving as well as concept formation. Anxiety, depression and attention deficit hyperkinetic disorders are the most common psychiatric co-morbidities seen. Investigating a child with epilepsy for cognitive and behavioral impairment is difficult as these tests would require cooperation from the patient's side to a significant extent. A rational approach towards treatment would be judicious selection of antiepileptic drugs, treatment of underlying cause, appropriate management of behavioral co-morbidities including psychopharmacotherapy and a trial of immunotherapy (particularly in cognitive epilepsies), wherever appropriate.
Genetics of Severe Early Onset Epilepsies
2017-08-24
Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions
Comprehensive Epilepsy Program.
ERIC Educational Resources Information Center
Virginia Univ., Charlottesville. Comprehensive Epilepsy Program.
The paper describes the Comprehensive Epilepsy Program at the University of Virginia Medical Center and includes information on the following topics: basic questions about epilepsy; describing and recording seizure activity; first aid in seizure care; the inpatient and outpatient educational service component; admission and referral; international…
Wirrell, Elaine C; Grossardt, Brandon R; So, Elson L; Nickels, Katherine C
2011-01-01
Purpose To compare long-term outcome in a population-based group of children with cryptogenic vs symptomatic focal epilepsy diagnosed from 1980–2004 and to define the course of epilepsy in the cryptogenic group. Methods We identified all children residing in Olmsted County, MN, 1 month through 17 years with newly diagnosed, non-idiopathic focal epilepsy from 1980–2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long-term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings Of 359 children with newly-diagnosed epilepsy, 215 (60%) had non-idiopathic focal epilepsy. Of these, 206 (96%) were followed for more than 12 months. Ninety five children (46%) were classified as symptomatic. Median follow-up from diagnosis was similar in both groups, being 157 months (25%ile, 75%ile 89, 233) in the cryptogenic group vs 134 months (25%ile, 75%ile 78, 220) in the symptomatic group (p=0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long-term outcome was significantly better in those with cryptogenic vs symptomatic etiology (intractable epilepsy at last follow-up, 7% vs 40%, p<0.001; seizure-freedom at last follow-up, 81% vs 55%, p<0.001). Of those who achieved seizure-freedom at final follow-up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p=0.01). One third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure-free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly
Friedman, Daniel; Fahlstrom, Robyn
2013-12-01
Little is known about the ethnic and racial differences in the prevalence of generalized and focal epilepsy among patients with non-acquired epilepsies. In this study, we examined epilepsy classification and race/ethnicity in 813 probands from sibling or parent-child pairs with epilepsy enrolled in the Epilepsy Genome/Phenome Project (EPGP). Subjects were classified as generalized epilepsy (GE), non-acquired focal epilepsy (NAFE), mixed epilepsy syndrome (both generalized and focal), and unclassifiable, based on consensus review of semiology and available clinical, electrophysiology, and neuroimaging data. In this cohort, 628 (77.2%) subjects identified exclusively as Caucasian/white and 65 (8.0%) subjects reported African ancestry, including subjects of mixed-race. Of the Caucasian/white subjects, 357 (56.8%) had GE, 207 (33.0%) had NAFE, 32 (5.1%) had a mixed syndrome, and 32 (5.1%) were unclassifiable. Among subjects of African ancestry, 28 (43.1%) had GE, 27 (41.5%) had NAFE, 2 (3.1%) had a mixed syndrome, and 8 (12.3%) were unclassifiable. There was a higher proportion of subjects with GE compared to other syndromes among Caucasians/whites compared to subjects with African ancestry (OR 1.74, 95% CI: 1.04-2.92, two-tailed Fisher's exact test, p=0.036). There was no difference in the rate of GE among subjects reporting Hispanic ethnicity (7.6% of total) when adjusted for race (Caucasian/white vs non-Caucasian/white; OR 0.65, 95% CI: 0.40-1.06, p>0.05). The proportion of participants with unclassifiable epilepsy was significantly greater in those of African-American descent. In a group of patients with epilepsy of unknown etiology and an affected first degree relative, GE is more common among Caucasian/white subjects than among those with African ancestry. These findings suggest there may be geographical differences in the distribution of epilepsy susceptibility genes and an effect of genetic background on epilepsy phenotype. However, the results should be
Warner, Timothy A.; Shen, Wangzhen; Huang, Xuan; Liu, Zhong; Macdonald, Robert L.; Kang, Jing-Qiong
2016-01-01
Genetic epilepsy is a common disorder with phenotypic variation, but the basis for the variation is unknown. Comparing the molecular pathophysiology of mutations in the same epilepsy gene may provide mechanistic insights into the phenotypic heterogeneity. GABRG2 is an established epilepsy gene, and mutations in it produce epilepsy syndromes with varying severities. The disease phenotype in some cases may be caused by simple loss of subunit function (functional haploinsufficiency), while others may be caused by loss-of-function plus dominant negative suppression and other cellular toxicity. Detailed molecular defects and the corresponding seizures and related comorbidities resulting from haploinsufficiency and dominant negative mutations, however, have not been compared. Here we compared two mouse models of GABRG2 loss-of-function mutations associated with epilepsy with different severities, Gabrg2+/Q390X knockin (KI) and Gabrg2+/- knockout (KO) mice. Heterozygous Gabrg2+/Q390XKI mice are associated with a severe epileptic encephalopathy due to a dominant negative effect of the mutation, while heterozygous Gabrg2+/- KO mice are associated with mild absence epilepsy due to simple haploinsufficiency. Unchanged at the transcriptional level, KI mice with severe epilepsy had neuronal accumulation of mutant γ2 subunits, reduced remaining functional wild-type subunits in dendrites and synapses, while KO mice with mild epilepsy had no intracellular accumulation of the mutant subunits and unaffected biogenesis of the remaining wild-type subunits. Consequently, KI mice with dominant negative mutations had much less wild-type receptor expression, more severe seizures and behavioural comorbidities than KO mice. This work provides insights into the pathophysiology of epilepsy syndrome heterogeneity and designing mechanism-based therapies. PMID:27340224
Norwood, Braxton A.; Bumanglag, Argyle V.; Osculati, Francesco; Sbarbati, Andrea; Marzola, Pasquina; Nicolato, Elena; Fabene, Paolo F.; Sloviter, Robert S.
2010-01-01
In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called “classic hippocampal sclerosis.” No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive “endstage” pathology resulting from years of spontaneous seizures. We posed the alternate hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30-minute episodes of perforant pathway stimulation in Sprague-Dawley rats increased granule cell paired-pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8-hour episode of reduced-intensity stimulation in Long-Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal-onset seizures began 16–25 days post-injury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically “cryptic” excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. PMID
[Tropical causes of epilepsy].
Carod-Artal, F J
Eighty-five percent of all epileptics live in tropical regions. Prenatal risk factors, traumatic brain injuries and different parasitic infestations of the central nervous system (CNS) are the reasons behind the high prevalence of epilepsy. This work reviews the main parasitic infestations causing epilepsy in the tropics. Neurocysticercosis is the main cause of focal epilepsy in early adulthood in endemic areas (30-50%). All the phases of cysticerci (viable, transitional and calcified) are associated with epileptic seizures. Anti-cysticercus treatment helps get rid of cysticerci faster and reduces the risk of recurrence of seizures in patients with viable cysts. Symptomatic epilepsy can be the first manifestation of neuroschistosomiasis in patients without any systemic symptoms. The pseudotumoral form can trigger seizures secondary to the presence of granulomas and oedemas in the cerebral cortex. The eggs of Schistosoma japonicum are smaller, reach the CNS more easily and trigger epileptic seizures more frequently. Toxocariasis and sparganosis are other parasitic infestations that can give rise to symptomatic seizures. The risk factors for suffering chronic epilepsy after cerebral malaria are a positive familial history of epilepsy and a history of episodes of fever and cerebral malaria that began with coma or which progressed with multiple, prolonged epileptic seizures. About 20% of patients with cerebral infarction secondary to Chagas disease present late vascular epilepsy as a complication. Very few studies have been conducted to examine the prognosis, risk of recurrence and modification of the natural course of seizures associated with tropical parasitic infestations, except for the case of neurocysticercosis.
Bruno, Elisa; Bartoloni, Alessandro; Sofia, Vito; Rafael, Florentina; Magnelli, Donata; Padilla, Sandra; Quattrocchi, Graziella; Bartalesi, Filippo; Segundo, Higinio; Zappia, Mario; Preux, Pierre-Marie; Nicoletti, Alessandra
2012-09-01
Epilepsy is associated with a significant burden of social stigma that appears to be influenced by psychosocial and cultural factors. Stigma has a negative effect on the management of people with epilepsy (PWE), representing one of the major factors that contribute to the burden of epilepsy. To assess stigma perception among the Guarani population, one hundred thirty-two people living in Guaraní communities in Bolivia were invited to complete the Stigma Scale of Epilepsy questionnaire. The main determinants of stigma identified were: the fear linked to loss of control, the feelings of sadness and pity toward PWE, the difficulties faced by PWE in the professional and relationship fields, the level of education and type of seizure. Our study pointed out that, in this population, PWE face difficulties in everyday life because of epilepsy-associated stigma and the results attest to the importance of promoting community-based educational programs aimed at reducing the stigmatization process. Copyright © 2012 Elsevier Inc. All rights reserved.
Determinants of felt stigma in epilepsy.
Aydemir, N; Kaya, B; Yıldız, G; Öztura, I; Baklan, B
2016-05-01
The present study aimed to determine the level of felt stigma, overprotection, concealment, and concerns related to epilepsy in different life domains by using culturally-specific scales for Turkish individuals with epilepsy. Also, it aimed to detect relations among the study variables and to determine the variables which predict felt stigma. For this purpose, felt stigma scale, overprotection scale, concealment of epilepsy scale, and concerns of epilepsy scale were administered to two hundred adult persons with epilepsy (PWE). The results showed that almost half of the participants reported felt stigma, overprotection, concealment of epilepsy, concerns related to future occupation, and concerns related to social life. Almost all the study variables show correlations with each other. Concealment of epilepsy, concerns related to social life, and concerns related to future occupation were found as the predictors of felt stigma. Copyright © 2016 Elsevier Inc. All rights reserved.
Anthropometric Indices in Children With Refractory Epilepsy.
Aminzadeh, Vahid; Dalili, Setila; Ashoorian, Yalda; Kohmanaee, Shahin; Hassanzadeh Rad, Afagh
2016-01-01
We aimed to assess the effect of body mass index (BMI) on reducing the risk of refractory seizure due to lipoid tissue factors. This matched case-control study, consisted of cases (Patients with refractory epilepsy) and controls (Healthy children) referred to 17 Shahrivar Hospital, Guilan University of Medical Sciences, Guilan, Iran during 2013-2014. Data were gathered by a form including demographic characteristics, type of epilepsy, predominant time of epilepsy, therapeutic approach, frequency of epilepsy, time of disease onset and anthropometric indices. We measured anthropometric indices and transformed them into Z-scores. Data were reported by descriptive statistics (mean and standard deviation) and analyzed by Pearson correlation coefficient, paired t test and multinomial regression analysis test using SPSS 19. There was no significant difference between sex groups regarding anthropometric indices. Generalized and focal types of epilepsies were noted on 57.5% and 38.75% of patients, respectively. Daytime epilepsies happened in 46.25% of patients and 33.75% noted no predominant time for epilepsies. Clinicians indicated poly-therapy for the majority of patients (92.5%). The most common onset times for epilepsies were 36-72 months for 32.5% of patients. Lower onset time indicated lower frequency of refractory epilepsies. Although, there was significant difference between Zheight and predominant time of epilepsies but no significant relation was found between types of epilepsies and frequency of epilepsies with anthropometric indices. Using multivariate regression analysis by backward LR, Zweight and birth weight were noted as the predicting factors of refractory epilepsies. This effect may be because of leptin. Therefore, researchers recommend further investigations regarding this issue in children with epilepsy.
Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy.
Lv, Rui-Juan; Ren, Hai-Tao; Guan, Hong-Zhi; Cui, Tao; Shao, Xiao-Qiu
2018-02-01
The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size. This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period. A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%), anti-GABA B -R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures. This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new-onset seizures in isolation or with a seizure-predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural-specific autoantibodies does not rule out AE.
Understanding Death in Children With Epilepsy.
Donner, Elizabeth J; Camfield, Peter; Brooks, Linda; Buchhalter, Jeffrey; Camfield, Carol; Loddenkemper, Tobias; Wirrell, Elaine
2017-05-01
Death in children with epilepsy is profoundly disturbing, with lasting effects on the family, community, and health care providers. The overall risk of death for children with epilepsy is about ten times that of the general population. However, the risk of premature death for children without associated neurological comorbidities is similar to that of the general population, and most deaths are related to the cause of the epilepsy or associated neurological disability, not seizures. The most common cause of seizure-related death in children with epilepsy is sudden unexpected death in epilepsy (SUDEP). SUDEP is relatively uncommon in childhood, but the risk increases if epilepsy persists into adulthood. Although the direct cause of SUDEP remains unknown, most often death follows a generalized convulsive seizure and the risk of SUDEP is strongly related to drug-resistant epilepsy and frequent generalized tonic-clonic seizures. The most effective SUDEP prevention strategy is to reduce the frequency of seizures, although a number of seizure detection devices are under development and in the future may prove to be useful for seizure detection for those at particularly high risk. There are distinct benefits for health care professionals to discuss mortality with the family soon after the diagnosis of epilepsy. An individual approach is appropriate. When a child with epilepsy dies, particularly if the death was unexpected, family grief may be profound. Physicians and other health care professionals have a critical role in supporting families that lose a child to epilepsy. This review will provide health care providers with information needed to discuss the risk of death in children with epilepsy and support families following a loss. Copyright © 2017 Elsevier Inc. All rights reserved.
Serafini, Anna; Lukas, Rimas V; VanHaerents, Stephen; Warnke, Peter; Tao, James X; Rose, Sandra; Wu, Shasha
2016-08-01
Epilepsy can be a manifestation of paraneoplastic syndromes which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting other organs and tissues. The antibodies commonly found in paraneoplastic encephalitis can be divided into two main groups depending on the target antigen: 1) antibodies against neuronal cell surface antigens, such as against neurotransmitter (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid (GABA)) receptors, ion channels (voltage-gated potassium channel (VGKC)), and channel-complex proteins (leucine rich, glioma inactivated-1 glycoprotein (LGI1) and contactin-associated protein-2 (CASPR2)) and 2) antibodies against intracellular neuronal antigens (Hu/antineuronal nuclear antibody-1 (ANNA-1), Ma2/Ta, glutamate decarboxylase 65 (GAD65), less frequently to CV2/collapsin response mediator protein 5 (CRMP5)). In this review, we provide a comprehensive survey of the current literature on paraneoplastic epilepsy indexed by the associated onconeuronal antibodies. While a range of seizure types can be seen with paraneoplastic syndromes, temporal lobe epilepsy is the most common because of the association with limbic encephalitis. Early treatment of the paraneoplastic syndrome with immune modulation/suppression may prevent the more serious potential consequences of paraneoplastic epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.
Leu, Costin; de Kovel, Carolien G F; Zara, Federico; Striano, Pasquale; Pezzella, Marianna; Robbiano, Angela; Bianchi, Amedeo; Bisulli, Francesca; Coppola, Antonietta; Giallonardo, Anna Teresa; Beccaria, Francesca; Trenité, Dorothée Kasteleijn-Nolst; Lindhout, Dick; Gaus, Verena; Schmitz, Bettina; Janz, Dieter; Weber, Yvonne G; Becker, Felicitas; Lerche, Holger; Kleefuss-Lie, Ailing A; Hallman, Kerstin; Kunz, Wolfram S; Elger, Christian E; Muhle, Hiltrud; Stephani, Ulrich; Møller, Rikke S; Hjalgrim, Helle; Mullen, Saul; Scheffer, Ingrid E; Berkovic, Samuel F; Everett, Kate V; Gardiner, Mark R; Marini, Carla; Guerrini, Renzo; Lehesjoki, Anna-Elina; Siren, Auli; Nabbout, Rima; Baulac, Stephanie; Leguern, Eric; Serratosa, Jose M; Rosenow, Felix; Feucht, Martha; Unterberger, Iris; Covanis, Athanasios; Suls, Arvid; Weckhuysen, Sarah; Kaneva, Radka; Caglayan, Hande; Turkdogan, Dilsad; Baykan, Betul; Bebek, Nerses; Ozbek, Ugur; Hempelmann, Anne; Schulz, Herbert; Rüschendorf, Franz; Trucks, Holger; Nürnberg, Peter; Avanzini, Giuliano; Koeleman, Bobby P C; Sander, Thomas
2012-02-01
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31
Malheiros, Jackeline M.; Polli, Roberson S.; Paiva, Fernando F.; Longo, Beatriz M.; Mello, Luiz E.; Silva, Afonso C.; Tannús, Alberto; Covolan, Luciene
2012-01-01
Summary Purpose Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well-established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE). Methods To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was co-administered with Pilo in a sub-group of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo-Timm histological labeling of zinc mossy fiber terminals in the dentate gyrus (DG). Key findings Chronically epileptic rats displaying MFS as detected by neo-Timm histology had a hyperintense MEMRI signal in the DG, while chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to non-epileptic control animals. A strong correlation (r = 0.81, P<0.001) was found between MEMRI signal enhancement and MFS. Significance This study shows that MEMRI is an attractive non-invasive method to detect mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy. PMID:22642664
Absence of diamine oxidase activity from rabbit and rat lungs.
Rao, S B; Rao, K S; Mehendale, H M
1986-01-01
To study the presence of diamine oxidase (DAO) activity in any tissue with putrescine as the substrate, it is necessary to use inhibitors to block all pathways that could further metabolize gamma-aminobutyraldehyde, which is the product of enzyme reaction. It is also necessary to inhibit any enzyme that may convert putrescine into higher polyamines. By this approach it was observed that lung tissue of both rat and rabbit exhibited no DAO activity. DAO activity was observed in the rat and rabbit intestine, the former showing 3 times as much activity as the latter. The other potential pathways of putrescine metabolism are of no consequence in the rat and rabbit intestine and lungs. PMID:3087348
Pediatric Epilepsy: Neurology, Functional Imaging, and Neurosurgery.
Mountz, James M; Patterson, Christina M; Tamber, Mandeep S
2017-03-01
In this chapter we provide a comprehensive review of the current role that functional imaging can have in the care of the pediatric epilepsy patient from the perspective of the epilepsy neurologist and the epilepsy neurosurgeon. In the neurology section, the diagnosis and classification of epilepsy adapted by the International League Against Epilepsy as well as the etiology and incidence of the disease is presented. The neuroimaging section describes how advanced nuclear medicine imaging methods can be synergized to provide a maximum opportunity to localize an epileptogenic focus. This section described the value of FDG-PET and regional cerebral blood flow SPECT in the identification of an epileptogenic focus. The imaging section also emphasizes the importance on developing a dedicated epilepsy management team, comprised of an epilepsy imaging specialist, epilepsy neurologist and epilepsy neurosurgeon, to provide the maximum benefit to each child with epilepsy. An emphasis is placed on preparation for ictal SPECT injection procedures, including the critical role of an automated injector well as the use of state-of-the-art dedicated nuclear medicine imaging and analysis protocols to correctly localize the epileptogenic focus location. In the final section, surgical options, approaches and expected outcomes for the different classes of epilepsy is presented. Copyright © 2017 Elsevier Inc. All rights reserved.
Unnwongse, Kanjana; Wehner, Tim; Foldvary-Schaefer, Nancy
2012-10-01
Mesial frontal lobe epilepsies can be divided into epilepsies arising from the anterior cingulate gyrus and those of the supplementary sensorimotor area. They provide diagnostic challenges because they often lack lateralizing or localizing features on clinical semiology and interictal and ictal scalp electroencephalographic (EEG) recordings. A number of unique semiologic features have been described over the last decade in patients with mesial frontal lobe epilepsy (FLE). There are few reports of applying advanced neurophysiologic techniques such as electrical source imaging, magnetoencephalography, EEG/functional magnetic resonance imaging, or analysis of high-frequency oscillations in patients with mesial FLE. Despite these diagnostic challenges, it seems that patients with mesial FLE benefit from epilepsy surgery to the same extent or even better than patients with FLE do, as a whole.
History of Neuropsychology Through Epilepsy Eyes
Loring, David W.
2010-01-01
In the 19th century, Hughlings Jackson relied on clinical history, seizure semiology, and the neurologic examination as methods for seizure localization to inform the first epilepsy surgeries. In the 20th century, psychological and neuropsychological tests were first employed as both diagnostic and prognostic measures. The contemporary practice of epilepsy evaluation and management includes neuropsychology as a critical component of epilepsy care and research, and epilepsy and neuropsychology have enjoyed a very special and synergistic relationship. This paper reviews how epilepsy has shaped the practice of neuropsychology as a clinical service by asking critical questions that only neuropsychologists were in a position to answer, and how clinical care of epilepsy patients has been significantly improved based on neuropsychology's unique contributions. PMID:20395259
The causes of epilepsy: changing concepts of etiology of epilepsy over the past 150 years.
Shorvon, Simon D
2011-06-01
This paper provides a survey of the changing concepts of the etiology of epilepsy from 1860 to 2010, focusing on the first two 50-year periods and outlining more briefly major developments in the past 50 years. Among the concepts reviewed in the first 100 years are: the division between predisposing and exciting causes, idiopathic and genuine epilepsy, organic epilepsy, the concept of "cause" being equivalent to "causal mechanism," Russell Reynolds etiological classification, the neurological taint and theories of degeneration, the self-perpetuating nature of seizures, reflex theories of etiology, autointoxication, heredity and eugenics, epilepsy due to brain disorders, the role of EEG and of hippocampal sclerosis, psychological theories of causation, and the multifactorial view of epilepsy etiology. In the past 50 years, the major advances in studying causation in epilepsy have been: clinical biochemistry, neuroimaging, molecular genetics, studies of mechanisms of epilepsy, better statistical methodologies and classification. A number of general observations can be made: the identification of "cause" is not as simple as it might at first appear; progress in the study of causation has been often erratic and travelled up many cul-de-sacs; theories of causation are heavily influenced by societal influences and fashion, and is also heavily dependent on applied methodologies; the recently explored possibility that the underlying inherited mechanisms of epilepsy are shared with other neuropsychiatric conditions is in effect a reinvention of the concept of the neurological trait, and this has ethical and social implications. Considering and classifying cause in terms of causal mechanism, as was suggested by Hughlings Jackson, is an ultimate goal. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Modi, Avani C; Junger, Katherine F; Mara, Constance A; Kellermann, Tanja; Barrett, Lauren; Wagner, Janelle; Mucci, Grace A; Bailey, Laurie; Almane, Dace; Guilfoyle, Shanna M; Urso, Lauryn; Hater, Brooke; Hustzi, Heather; Smith, Gigi; Herrmann, Bruce; Perry, M Scott; Zupanc, Mary; Varni, James W
2017-11-01
To validate a brief and reliable epilepsy-specific, health-related quality of life (HRQOL) measure in children with various seizure types, treatments, and demographic characteristics. This national validation study was conducted across five epilepsy centers in the United States. Youth 5-18 years and caregivers of youth 2-18 years diagnosed with epilepsy completed the PedsQL Epilepsy Module and additional questionnaires to establish reliability and validity of the epilepsy-specific HRQOL instrument. Demographic and medical data were collected through chart reviews. Factor analysis was conducted, and internal consistency (Cronbach's alphas), test-retest reliability, and construct validity were assessed. Questionnaires were analyzed from 430 children with epilepsy (M age = 9.9 years; range 2-18 years; 46% female; 62% white: non-Hispanic; 76% monotherapy, 54% active seizures) and their caregivers. The final PedsQL Epilepsy Module is a 29-item measure with five subscales (i.e., Impact, Cognitive, Sleep, Executive Functioning, and Mood/Behavior) with parallel child and caregiver reports. Internal consistency coefficients ranged from 0.70-0.94. Construct validity and convergence was demonstrated in several ways, including strong relationships with seizure outcomes, antiepileptic drug (AED) side effects, and well-established measures of executive, cognitive, and emotional/behavioral functioning. The PedsQL Epilepsy Module is a reliable measure of HRQOL with strong evidence of its validity across the epilepsy spectrum in both clinical and research settings. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Why epilepsy challenges social life.
Steiger, Bettina K; Jokeit, Hennric
2017-01-01
Social bonds are at the center of our daily living and are an essential determinant of our quality of life. In people with epilepsy, numerous factors can impede cognitive and affective functions necessary for smooth social interactions. Psychological and psychiatric complications are common in epilepsy and may hinder the processing of social information. In addition, neuropsychological deficits such as slowed processing speed, memory loss or attentional difficulties may interfere with enjoyable reciprocity of social interactions. We consider societal, psychological, and neuropsychological aspects of social life with particular emphasis on socio-cognitive functions in temporal lobe epilepsy. Deficits in emotion recognition and theory of mind, two main aspects of social cognition, are frequently observed in individuals with mesial temporal lobe epilepsy. Results from behavioural studies targeting these functions will be presented with a focus on their relevance for patients' daily life. Furthermore, we will broach the issue of pitfalls in current diagnostic tools and potential directions for future research. By giving a broad overview of individual and interpersonal determinants of social functioning in epilepsy, we hope to provide a basis for future research to establish social cognition as a key component in the comprehensive assessment and care of those with epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Smith, Mary Lou
2016-11-01
The new approach to classification of the epilepsies emphasizes the role of dysfunction in networks in defining types of epilepsies. This paper reviews the structural and neuropsychological deficits in two types of childhood epilepsy: frontal lobe and temporal lobe epilepsy. The evidence for and against a pattern of specificity of deficits in executive function and memory associated with these two types of epilepsies is presented. The evidence varies with the methodologies used in the studies, but direct comparison of the two types of epilepsies does not suggest a clear-cut mapping of function onto structure. These findings are discussed in light of the concept of network dysfunction. The evidence supports the conceptualization of epilepsy as a network disease. Implications for future work in the neuropsychology of pediatric epilepsy are suggested. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.
A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats
Morales, Juan Carlos; Álvarez-Ferradas, Carla; Roncagliolo, Manuel; Fuenzalida, Marco; Wellmann, Mario; Nualart, Francisco Javier; Bonansco, Christian
2014-01-01
Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other
A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats.
Morales, Juan Carlos; Alvarez-Ferradas, Carla; Roncagliolo, Manuel; Fuenzalida, Marco; Wellmann, Mario; Nualart, Francisco Javier; Bonansco, Christian
2014-01-01
Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other
Epilepsy and violence: case series concerning physical trauma in children of persons with epilepsy
Gauffin, Helena; Landtblom, Anne-Marie
2014-01-01
Historically, epilepsy has been associated with violence, but more recent studies have emphasized genetic and psychosocial factors as more important. The case series presented here aim to highlight the difficult situation the affected children are in. We report on three cases when children have been traumatized and, in one case, even been killed by their parent who was diagnosed with epilepsy. In the first case, we describe a woman with juvenile myoclonic epilepsy who was sentenced to forensic psychiatry care for killing her child. She lived under difficult psychosocial circumstances and a suicide attempt contributed to what happened. The second case describes a man with post-traumatic seizures who was sentenced for child abuse. Ictal or postictal violence was considered in these two cases but a causal link between the violence and epilepsy has not been established. In the third case, we describe a woman with focal epilepsy and psychogenic non-epileptic seizures (PNESs). Her child was hurt and frightened in relation to violent seizures, which were regarded as PNESs. This case series demonstrates that children of parents with epilepsy can be in a vulnerable situation. No causality has been established between the seizures and these events, so consequently other factors such as psychosocial stress, low cognitive function, and a suicide attempt must also be considered as important. When a child is hurt by a parent with epilepsy the patient must be closely examined to determine the role of the seizures. Children can also be affected by PNESs. It is essential to notice especially those children of parents with epilepsy who live under difficult psychosocial circumstances and offer extra support when necessary. PMID:25484586
Temporal plus epilepsy: Anatomo-electroclinical subtypes
Andrade-Machado, René; Benjumea-Cuartas, Vanessa
2016-01-01
Background: Mesial temporal lobe epilepsy (TLE) is a remediable epileptic syndrome. About 40% of patients continue to have seizures after standard temporal lobectomy. It has been suggested that some of these patients could actually suffer from a more complex epileptogenic network. Because a few papers have been dedicated to this topic, we decided to write an article updating this theme. Methods: We performed a literature search using the following terminology: “temporal plus epilepsy and networks,” “temporal plus epilepsy,” “orbito-temporal epilepsy,” “temporo-insular epilepsy,” “temporo-parieto-occipital (TPO) epilepsy,” “parieto-temporal epilepsy,” “intracortical evoked potential and temporal plus epilepsy,” “temporal lobe connectivity and epilepsy,” “intracortical evoked potential and epilepsy surgery,” “role of extratemporal structures in TLE,” “surgical failure after temporal lobectomy,” “Diffusion tensor imaging (DTI) and temporal epilepsy,” and “positron emission tomography (PET) in temporal plus lobe epilepsy” in the existing PubMed databases. We searched only English and Spanish literature. Only papers that fit with the above-mentioned descriptors were included as part of the evidence. Other articles were used to reference some aspects of the temporal plus epilepsy. Results: A total of 48 papers from 2334 were revised. The most frequently reported auras in these groups of patients are gustatory hallucinations, vestibular illusions, laryngeal and throat constriction, atypical distribution of somatosensory symptoms (perioral and hands, bilaterally hands paresthesias, trunk and other). The most common signs are tonic posturing, hemifacial twist, and frequent bilateral clonic movements. Interictal electroencephalographic (EEG) patterns exhibit regional and frequently bilateral spikes and/or slow waves. The first ictal electrographic change is mostly regional. It is important to note that the evidence is
Musical and poetic creativity and epilepsy.
Hesdorffer, Dale C; Trimble, Michael
2016-04-01
Associations between epilepsy and musical or poetic composition have received little attention. We reviewed the literature on links between poetic and musical skills and epilepsy, limiting this to the Western canon. While several composers were said to have had epilepsy, John Hughes concluded that none of the major classical composers thought to have had epilepsy actually had it. The only composer with epilepsy that we could find was the contemporary composer, Hikari Oe, who has autism and developed epilepsy at age 15years. In his childhood years, his mother found that he had an ability to identify bird sound and keys of songs and began teaching him piano. Hikari is able to compose in his head when his seizures are not severe, but when his seizures worsen, his creativity is lost. Music critics have commented on the simplicity of his musical composition and its monotonous sound. Our failure to find evidence of musical composers with epilepsy finds parallels with poetry where there are virtually no established poets with epilepsy. Those with seizures include Lord George Byron in the setting of terminal illness, Algernon Swinburne who had alcohol-related seizures, Charles Lloyd who had seizures and psychosis, Edward Lear who had childhood onset seizures, and Vachel Lindsay. The possibility that Emily Dickinson had epilepsy is also discussed. It has not been possible to identify great talents with epilepsy who excel in poetic or musical composition. There are few published poets with epilepsy and no great composers. Why is this? Similarities between music and poetry include meter, tone, stress, rhythm, and form, and much poetry is sung with music. It is likely that great musical and poetic compositions demand a greater degree of concentration and memory than is possible in epilepsy, resulting in problems retaining a musical and mathematical structure over time. The lack of association between recognizable neuropsychiatric disorders and these skills is a gateway to
Genetics Home Reference: pyridoxine-dependent epilepsy
... Home Health Conditions Pyridoxine-dependent epilepsy Pyridoxine-dependent epilepsy Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in ...
Emory, Hamlin; Wells, Christopher; Mizrahi, Neptune
2015-07-01
Two adolescent females with absence epilepsy were classified, one as attention deficit and the other as bipolar disorder. Physical and cognitive exams identified hypotension, bradycardia, and cognitive dysfunction. Their initial electroencephalograms (EEGs) were considered slightly slow, but within normal limits. Quantitative EEG (QEEG) data included relative theta excess and low alpha mean frequencies. A combined treatment of antiepileptic drugs with a catecholamine agonist/reuptake inhibitor was sequentially used. Both patients' physical and cognitive functions improved and they have remained seizure free. The clinical outcomes were correlated with statistically significant changes in QEEG measures toward normal Z-scores in both anterior and posterior regions. In addition, low resolution electromagnetic tomography (LORETA) Z-scored source correlation analyses of the initial and treated QEEG data showed normalized patterns, supporting a neuroanatomic resolution. This study presents preliminary evidence for a neurophysiologic approach to patients with absence epilepsy and comorbid disorders and may provide a method for further research. © EEG and Clinical Neuroscience Society (ECNS) 2014.
Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie
2017-01-01
The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden
Saipetch, Chutima; Sachs, Ezekiel
2016-01-01
Abstract Purpose of review: Technological advance has revolutionized epilepsy management recently. Herein, we review some recent developments. Recent findings: Responsive neurostimulation (Food and Drug Administration [FDA]-approved 2013) works by continuous analysis of brain rhythms and direct brain stimulation on detecting patterns thought to be epileptogenic, thereby aborting seizures. Cardio-responsive vagus nerve stimulation (FDA-approved 2015) is an improvement over traditional vagus nerve stimulation systems, taking advantage of the fact that 80% of seizures are associated with tachycardia. Automated tachycardia detection leads to vagus nerve stimulation to abort seizures. In MRI-guided stereotactic laser ablation (developed 2012), a directed laser emitting fiberoptic catheter is used to ablate epileptogenic lesions. The procedure can be completed in 3 to 4 hours, potentially under local anesthesia and with next-day discharge. Perampanel (FDA-approved 2012) is a promising new class of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-antagonist antiseizure therapy. Meanwhile, a millennia-old remedy for epilepsy, cannabis, is staging a comeback with recent legal and social permissiveness accelerating research into this use. Summary: The coming years will demonstrate how these recent advances in device and drug management will improve the care of epilepsy. PMID:29443283
Evaluation of Cardiovascular Risk Factors in the Wistar Audiogenic Rat (WAR) Strain
Fazan, Rubens; Silva, Carlos Alberto A.; Oliveira, José Antônio Cortes; Salgado, Helio Cesar; Montano, Nicola; Garcia-Cairasco, Norberto
2015-01-01
Introduction Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. Methods We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. Results Basal RR interval (RRi) was similar between WAR and Wistar rats (188±5 vs 199±6 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92±3 vs 115±5 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2±0.6 vs 5.6±1 mmHg) and volume (137±9 vs 68±9 μL) as well as lower rate of increase in ventricular pressure (5266±602 vs 7320±538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014±780 vs -7766±998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078±0.011 vs 0.036±0.011 mmHg.μL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. Conclusions The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy. PMID:26029918
Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy.
Knopp, Andreas; Kivi, Anatol; Wozny, Christian; Heinemann, Uwe; Behr, Joachim
2005-03-21
The subiculum was recently shown to be crucially involved in the generation of interictal activity in human temporal lobe epilepsy. Using the pilocarpine model of epilepsy, this study examines the anatomical substrates for network hyperexcitability recorded in the subiculum. Regular- and burst-spiking subicular pyramidal cells were stained with fluorescence dyes and reconstructed to analyze seizure-induced alterations of the dendritic and axonal system. In control animals burst-spiking cells outnumbered regular-spiking cells by about two to one. Regular- and burst-spiking cells were characterized by extensive axonal branching and autapse-like contacts, suggesting a high intrinsic connectivity. In addition, subicular axons projecting to CA1 indicate a CA1-subiculum-CA1 circuit. In the subiculum of pilocarpine-treated rats we found an enhanced network excitability characterized by spontaneous rhythmic activity, polysynaptic responses, and all-or-none evoked bursts of action potentials. In pilocarpine-treated rats the subiculum showed cell loss of about 30%. The ratio of regular- and burst-spiking cells was practically inverse as compared to control preparations. A reduced arborization and spine density in the proximal part of the apical dendrites suggests a partial deafferentiation from CA1. In pilocarpine-treated rats no increased axonal outgrowth of pyramidal cells was observed. Hence, axonal sprouting of subicular pyramidal cells is not mandatory for the development of the pathological events. We suggest that pilocarpine-induced seizures cause an unmasking or strengthening of synaptic contacts within the recurrent subicular network. Copyright 2005 Wiley-Liss, Inc.
Sidhu, Meneka Kaur; Duncan, John S; Sander, Josemir W
2018-05-17
Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance.Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy.
Epilepsy, language, and social skills.
Caplan, Rochelle
2017-10-04
Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals' functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills. Copyright © 2017 Elsevier Inc. All rights reserved.
Holder, J. Lloyd; Quach, Michael M.
2017-01-01
Summary Objective The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability1. Individuals with loss of function mutations in SHANK3 have intellectual disability, autism and variably, epilepsy2–5. The spectrum of seizure semiologies and electroencephalographic (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately two percent of individuals with moderate to severe intellectual disabilities and one percent of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations. Methods A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss of function mutation in SHANK3 identified through whole exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset and efficacy of therapy were determined. Electroencephalograms were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist. Results There is a wide spectrum of seizure semiologies, frequencies and severity in individuals with SHANK3 mutations. There are no specific electroencephalographic abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure. Significance All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure which can be challenging to identify due to comorbid intellectual disability in individuals with
Erdogan, Mumin Alper; Yusuf, Dimas; Christy, Joanna; Solmaz, Volkan; Erdogan, Arife; Taskiran, Emin; Erbas, Oytun
2018-06-07
Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures. Laboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ). Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant. Dapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.
Cognition in epilepsy: current clinical issues of interest.
Witt, Juri-Alexander; Helmstaedter, Christoph
2017-04-01
This review provides an update and summary of recent neuropsychological findings in epilepsy focusing on three major clinical topics among the many developments in the field. We will critically outline the current state with regard to cognition in new-onset epilepsies, social cognition in epilepsy, and the long-term outcome of epilepsy surgery and the cognitive outcomes of superselective surgical procedures. Current studies indicate that neuropsychological impairments are prevalent already at the onset of epilepsy and even before, social cognition (i.e., emotion recognition and theory of mind) is impaired in different epilepsy populations, the long-term outcome of epilepsy surgery is mostly characterized by a stable or even improved cognitive status, and superselective epilepsy surgeries are associated with a promising neuropsychological outcome. The high prevalence of cognitive deficits around epilepsy onset challenges the assumption that epilepsy is the major cause of cognitive problems and calls for early neuropsychological diagnostics. Social cognition seems to be a relevant domain that is not yet routinely considered in epilepsy. The cognitive long-term outcome of epilepsy surgery is mostly positive. Stereotactic thermocoagulation and gamma knife surgery appear to be cognitively safe procedures.
Familial risk of epilepsy: a population-based study
Peljto, Anna L.; Barker-Cummings, Christie; Vasoli, Vincent M.; Leibson, Cynthia L.; Hauser, W. Allen; Buchhalter, Jeffrey R.
2014-01-01
Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935–94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives’ medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75–5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted ‘prenatal/developmental cause’ (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as ‘idiopathic’ or ‘unknown cause’), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93–15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92–4.00) for focal epilepsy. In relatives of
Sahoo, Satya S; Zhang, Guo-Qiang; Lhatoo, Samden D
2013-08-01
The epilepsy community increasingly recognizes the need for a modern classification system that can also be easily integrated with effective informatics tools. The 2010 reports by the United States President's Council of Advisors on Science and Technology (PCAST) identified informatics as a critical resource to improve quality of patient care, drive clinical research, and reduce the cost of health services. An effective informatics infrastructure for epilepsy, which is underpinned by a formal knowledge model or ontology, can leverage an ever increasing amount of multimodal data to improve (1) clinical decision support, (2) access to information for patients and their families, (3) easier data sharing, and (4) accelerate secondary use of clinical data. Modeling the recommendations of the International League Against Epilepsy (ILAE) classification system in the form of an epilepsy domain ontology is essential for consistent use of terminology in a variety of applications, including electronic health records systems and clinical applications. In this review, we discuss the data management issues in epilepsy and explore the benefits of an ontology-driven informatics infrastructure and its role in adoption of a "data-driven" paradigm in epilepsy research. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Myers, Kenneth A; Bello-Espinosa, Luis E; Symonds, Joseph D; Zuberi, Sameer M; Clegg, Robin; Sadleir, Lynette G; Buchhalter, Jeffrey; Scheffer, Ingrid E
2018-06-06
Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. We retrospectively evaluated HRV in epilepsy patients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.
Sexual problems in people with refractory epilepsy.
Henning, Oliver J; Nakken, Karl O; Træen, Bente; Mowinckel, Petter; Lossius, Morten
2016-08-01
Sexual dysfunction is an important but often neglected aspect of epilepsy. The objective of this study was to explore the prevalence and types of sexual problems in patients with epilepsy and compare the results with similar data obtained from a representative sample of the general population. At the National Centre for Epilepsy in Norway, 171 of 227 consecutive adult inpatients and outpatients with epilepsy (response rate: 75.3%) and their neurologists participated in a questionnaire study about epilepsy and sexuality. The results were compared with data available from 594 adult Norwegians who had completed the same questionnaire. Patients with epilepsy had a significantly higher prevalence of sexual problems (women: 75.3% vs. 12.0%; men: 63.3% vs. 9.6%). The most commonly reported problems (>30%) were reduced sexual desire, orgasm problems, erection problems, and vaginal dryness. The patients reported considerable dissatisfaction regarding sexual functioning. Significantly more sexual problems were found in patients of both sexes with reduced quality of life and in women with symptoms of depression. We found no significant association between sexual problems and age of epilepsy onset, type of epilepsy, or use of enzyme-inducing antiepileptic drugs. Whereas age at sexual debut did not differ between the patients with epilepsy and the general population, men with epilepsy had a lower number of partners during the last 12months, and the proportion of women with a low frequency of intercourse was higher in the group with epilepsy. In conclusion, sexual problems are significantly greater in Norwegian patients with epilepsy than in the general adult population. As no single epilepsy type or treatment could be identified as a specific predisposing factor, it seems likely that there are multiple causes underlying our results, including both organic and psychosocial factors. Copyright © 2016 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Goldman, Alica M.
2006-01-01
The chance that someone will develop any disease is influenced by heredity and environment. Epilepsy is not an exception. Everybody inherits a unique degree of susceptibility to seizures. About 3 percent of the United States population is prone to seizures and will get epilepsy at some point of their lives (1). Two thirds of the people with…
Stem cell therapy for treatment of epilepsy.
Goodarzi, Parisa; Aghayan, Hamid Reza; Soleimani, Masoud; Norouzi-Javidan, Abbas; Mohamadi-Jahani, Fereshteh; Jahangiri, Sharareh; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak
2014-01-01
Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious safety and ethical concerns that are needed to be eliminated before clinical application.
Methylphenidate, cognition, and epilepsy
Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J.; Loring, David W.; Meador, Kimford
2017-01-01
Objective: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. Methods: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Results: Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20–62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive “fogginess” (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. Conclusions: This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. ClinicalTrials.gov identifier: NCT02178995. Classification of evidence: This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. PMID:28031390
[Epilepsy-new diagnostic tools, old drugs? : Therapeutic consequences of epilepsy genetics].
Tacke, M; Neubauer, B A; Gerstl, L; Roser, T; Rémi, J; Borggraefe, I
2017-12-01
Recent advances in the field of epilepsy genetics have led to an increased fraction of patients with epilepsies where the etiology of the disease could be identified. Nevertheless, there is some criticism regarding the use of epilepsy genetics because in many cases the identification of a pathogenetic mutation does not lead to an adaptation of therapy or to an improved prognosis. In addition, the interpretation of genetic results might be complicated due to the considerable numbers of variants of unclear significance. This publication presents the arguments in favour of a broad use of genetic investigations for children with epilepsies. Several diseases where a genetic diagnosis does in fact have direct therapeutic consequences are mentioned. In addition, the indirect impact of an established etiology, encompassing the avoidance of unnecessary diagnostic measures, possibility of genetic counselling, and the easing of the psychologic burden for the caregivers, should not be underestimated. The arguments in favour of broad genetic diagnostics prevail notwithstanding the lack of relevant new developments regarding the therapy.
Walker, Elizabeth Reisinger; Barmon, Christina; McGee, Robin E.; Engelhard, George; Sterk, Claire E.; DiIorio, Colleen; Thompson, Nancy J.
2015-01-01
Epilepsy is a chronic condition that significantly affects the lives of individuals with epilepsy and their support persons, though few studies have examined the experiences of both individuals. To examine these experiences and explore the interpersonal relationships between dyad members, we conducted in-depth interviews with 22 people with epilepsy and 16 support persons. Data analysis was guided by a grounded theory perspective. We developed a model that shows how epilepsy impacts the lives of both people with epilepsy and support persons and how the experiences of people with epilepsy and supporters influence one another. The core model elements were seizure and treatment factors, relationship characteristics, self-management, seizure control, support provided, illness intrusiveness, and quality of life. People with epilepsy moved through the model in five trajectories depending on seizure control, relationship type, and gender. Support providers followed four trajectories based on seizure control, perception of burden, and support for themselves. People with epilepsy and their primary support providers have varied experiences in how epilepsy affects their lives. This model could serve as a basis for future research and intervention efforts focused on ways to reduce illness intrusiveness and improve quality of life for people with epilepsy and their supporters. PMID:26515151
Prognosis in epilepsy: initiating long-term drug therapy.
Mercadé Cerdá, J M; Mauri Llerda, J A; Becerra Cuñat, J L; Parra Gomez, J; Molins Albanell, A; Viteri Torres, C; López Gonzalez, F J; Salas Puig, X
2015-01-01
Prognosis in epilepsy refers to the probability of either achieving seizure remission (SR), whether spontaneously or using antiepileptic drugs (AED), or failing to achieve control of epileptic seizures (ES) despite appropriate treatment. Use of AED is recommended after a second unprovoked ES. For a first episode, the decision of whether or not to start drug treatment depends on the risk of recurrence and the advantages or disadvantages of the antiepileptic drug. The main goal of treatment is achieving absence of ES without adverse effects (AE). AED is selected according to epilepsy type and the demographic and clinical characteristics of the patient. A PubMed search located articles and recommendations by the most relevant scientific societies and clinical practice guidelines concerning epilepsy prognosis and treatment. Evidence and recommendations are classified according to the prognostic criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions. Most newly diagnosed epileptic patients achieve good control over their ES. The majority of the AEDs available at present provide effective control over all types of ES, and choice therefore depends on the patient's individual characteristics. Treatment should be initiated as monotherapy at the lowest effective dose, which in half of all patients provides ES control and is well tolerated. In cases in which the first AED is not effective, alternative therapy should be started, and monotherapy should be employed before combination therapy where possible. The probability of achieving good control over ES decreases with each successive treatment failure. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
Epilepsy and physical exercise.
Pimentel, José; Tojal, Raquel; Morgado, Joana
2015-02-01
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. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
[Economic aspects of epilepsy].
Argumosa, A; Herranz, J L
2000-06-01
The economic magnitude of epilepsy is determined by its effect on the employment status of the patients, the cost of drug treatment for them and the healthcare system and the repercussion worldwide. Studies of the cost of the disease show that it has economic importance due to the sum of the direct and indirect costs caused by it. In the case of epilepsy, the results of studies in various countries led to the creation of a Commission on Economic Aspects of Epilepsy. The lack of epidemiological studies regarding epilepsy in Spain may explain the lack of publications on this subject in our country. The percentage of the total cost due to antiepileptic drugs is considerable and will probably increase in the future. The pharmaco-economic evaluation made by cost-benefit, cost-effectiveness, cost-usefulness analysis and studies to minimize costs should serve to use healthcare resources in the most effective manner and justify the rational use of the new antiepileptic drugs. The economic impact of epilepsy is added to the repercussion of the disease itself on the patient and his family. The different distribution of costs in children and adults with epilepsy suggest the need for intervention at an early age to try to reduce the long term economic and personal repercussions. The pharmaco-economic evaluation of the new antiepileptic drugs will make it clear whether their considerable cost is worth paying for their greater effectivity.
Neurostimulation for Drug-Resistant Epilepsy
DeGiorgio, Christopher M.; Krahl, Scott E.
2013-01-01
Purpose of Review: The purpose of this review is to provide an evidence-based update on the neurostimulation options available for patients with drug-resistant epilepsy in the United States and in European countries. Recent Findings: The field of neurostimulation for epilepsy has grown dramatically since 1997, when vagus nerve stimulation became the first device to be approved for epilepsy by the US Food and Drug Administration (FDA). New data from recently completed randomized controlled trials are available for deep brain stimulation of the anterior thalamus, responsive neurostimulation, and trigeminal nerve stimulation. Although vagus nerve stimulation is the only device currently approved in the United States, deep brain stimulation and responsive neurostimulation devices are awaiting FDA approval. Deep brain stimulation, trigeminal nerve stimulation, and transcutaneous vagus nerve stimulation are now approved for epilepsy in the European Union. In this article, the mechanisms of action, safety, and efficacy of new neurostimulation devices are reviewed, and the key advantages and disadvantages of each are discussed. Summary: The exponential growth of the field of neuromodulation for epilepsy is an exciting development; these new devices provide physicians with new options for patients with drug-resistant epilepsy. PMID:23739108
Predictors of intractable childhood epilepsy.
Seker Yilmaz, Berna; Okuyaz, Cetin; Komur, Mustafa
2013-01-01
Our study sought to identify early predictive factors of medically intractable childhood epilepsy. A cohort of epileptic children from the city of Mersin was retrospectively investigated. All patients received care from the same Department of Pediatric Neurology. The epileptic cohort was divided into a drug-responsive epilepsy group and an intractable epilepsy group. Intractable epilepsy is defined as continued seizures in children despite adequate therapy with two or more antiepileptic drugs for more than 18 months. Strong univariate association was observed between intractability and several factors: age of onset, high initial seizure frequency, symptomatic etiology, mixed seizure types, previous history of status epilepticus, febrile and neonatal seizures, mental and motor developmental delay, multiple seizures in 1 day, electroencephalogram abnormalities, magnetic resonance imaging findings, and specific epileptic syndromes. Logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy. We suggest that medical intractability in childhood epilepsy can be predicted by monitoring these factors. Along with early prediction, alternative therapies may be designed to provide patients better seizure control and quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.
The Epidemiology of Global Epilepsy.
Singh, Anuradha; Trevick, Stephen
2016-11-01
The International League Against Epilepsy defines epilepsy as at least 2 unprovoked seizures more than 24 hours apart. It is a wide-reaching and complex illness affecting more than 70 million people worldwide and can take on a variety of forms, patterns, and severities. Geographic differences in the illness are often related to its etiology. A host of endemic illnesses and parasitic infections can lead to epilepsy syndromes. Management varies by region due to the availability of diagnostic modalities and medications. Treatment gaps in epilepsy care often are related to social and cultural factors that must also be understood. Copyright © 2016 Elsevier Inc. All rights reserved.
H.M. never again! An analysis of H.M.'s epilepsy and treatment.
Mauguière, F; Corkin, S
2015-03-01
On August 25, 1953, the patient H.M., aged 27, underwent a bilateral surgical destruction of the inner aspect of his temporal lobes performed by William Beecher Scoville with the aim to control H.M.'s drug refractory epileptic seizures and alleviate their impact on his quality of life. Postoperatively, H.M. presented for 55 years a "striking and totally unexpected grave loss of recent memories". This paper reports what we know about H.M.'s epilepsy before and after surgery and puts forward arguments supporting the syndromic classification of his epilepsy. We attempted to elucidate what could have been the rationale, in 1953, of Scoville's decision to carry out a bilateral ablation of H.M.'s medial temporal lobe structures, and we examined whether there was any convincing argument published before 1953 suggesting that bilateral hippocampal ablation could result in a permanent and severe amnesia. Our a posteriori analysis of H.M.'s medical history suggested that he was most probably suffering from idiopathic generalized epilepsy with absences and generalized convulsive seizures worsened by high dosage phenytoin treatment, or less probably from cryptogenic frontal lobe epilepsy. Importantly, he did not have temporal lobe epilepsy. Scoville based his proposal of bilateral mesial temporal lobe ablation on his experience as a psychosurgeon and on the assumption that the threshold of generalized epileptic activity could be lowered by some kind of hippocampal dysfunction potentially epileptic in nature. Given the scanty information on the link between amnesia and medial temporal lobe lesions that was available in humans in 1953, one can understand why Scoville was so surprised by the "striking and totally unexpected" memory loss he observed in H.M. after the bilateral ablation of his mesial temporal lobe structures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Sleep and Epilepsy: Strange Bedfellows No More.
St Louis, Erik K
2011-09-01
Ancient philosophers and theologians believed that altered consciousness freed the mind to prophesy the future, equating sleep with seizures. Only recently has the bidirectional influences of epilepsy and sleep upon one another received more substantive analysis. This article reviews the complex and increasingly recognized interrelationships between sleep and epilepsy. NREM sleep differentially activates interictal epileptiform discharges during slow wave (N3) sleep, while ictal seizure events occur more frequently during light NREM stages N1 and N2. The most commonly encountered types of sleep-related epilepsies (those with preferential occurrence during sleep or following arousal) include frontal and temporal lobe partial epilepsies in adults, and benign epilepsy of childhood with centrotemporal spikes (benign rolandic epilepsy) and juvenile myoclonic epilepsy in children and adolescents. Comorbid sleep disorders are frequent in patients with epilepsy, particularly obstructive sleep apnea in refractory epilepsy patients which may aggravate seizure burden, while treatment with nasal continuous positive airway pressure often improves seizure frequency. Distinguishing nocturnal events such as NREM parasomnias (confusional arousals, sleep walking, and night terrors), REM parasomnias including REM sleep behavior disorder, and nocturnal seizures if frequently difficult and benefits from careful history taking and video-EEG-polysomnography in selected cases. Differentiating nocturnal seizures from primary sleep disorders is essential for determining appropriate therapy, and recognizing co-existent sleep disorders in patients with epilepsy may improve their seizure burden and quality of life.
Social determinants of health in epilepsy.
Szaflarski, Magdalena
2014-12-01
Social factors have been identified as key drivers of epilepsy care, outcomes, and disparities, but there is a limited understanding of what these factors are and how they translate into disparities. This targeted review provides an overview of the social determinants of health framework and applies this perspective to the literature about social and psychosocial factors in epilepsy; a social determinants of health--epilepsy model is proposed. The key social determinants of health in epilepsy include socioeconomic status, race/ethnicity, age, and gender. For example, low socioeconomic status and minority status have been associated with a higher risk of epilepsy, more hospitalizations and emergency room visits (versus neurology services), antiepileptic drug nonadherence, and a lower rate of epilepsy surgery. Such differences in care/treatment and outcomes translate into health disparities, many of which are considered unjust (inequitable) and modifiable through social action. Other social determinants of health include structural and sociocultural contextual conditions (e.g., health economy, policy, and social stigma/discrimination) and mediating mechanisms including material (e.g., housing), behavioral/biological (e.g., adherence), psychosocial (e.g., perceived stigma), and health system (e.g., access) factors. There are complex relationships among social determinants of health in epilepsy, which remain poorly understood and hamper efforts to address and eliminate disparities in epilepsy care and outcomes. Further empirical work grounded in sound theory and robust methodologies is needed to identify points of intervention and design effective and socially acceptable solutions to any pervasive disparities in epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.
The epilepsy phenome/genome project.
Abou-Khalil, Bassel; Alldredge, Brian; Bautista, Jocelyn; Berkovic, Sam; Bluvstein, Judith; Boro, Alex; Cascino, Gregory; Consalvo, Damian; Cristofaro, Sabrina; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael; Fahlstrom, Robyn; Fiol, Miguel; Fountain, Nathan; Fox, Kristen; French, Jacqueline; Freyer Karn, Catharine; Friedman, Daniel; Geller, Eric; Glauser, Tracy; Glynn, Simon; Haas, Kevin; Haut, Sheryl; Hayward, Jean; Helmers, Sandra; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi; Knowlton, Robert; Kossoff, Eric; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel; McGuire, Shannon; Motika, Paul; Nesbitt, Gerard; Novotny, Edward; Ottman, Ruth; Paolicchi, Juliann; Parent, Jack; Park, Kristen; Poduri, Annapurna; Risch, Neil; Sadleir, Lynette; Scheffer, Ingrid; Shellhaas, Renee; Sherr, Elliott; Shih, Jerry J; Shinnar, Shlomo; Singh, Rani; Sirven, Joseph; Smith, Michael; Sullivan, Joe; Thio, Liu Lin; Venkat, Anu; Vining, Eileen; von Allmen, Gretchen; Weisenberg, Judith; Widdess-Walsh, Peter; Winawer, Melodie
2013-08-01
Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.
The representation of epilepsy in popular music.
Baxendale, Sallie
2008-01-01
Much can be learned about the contemporary stereotypes associated with epilepsy by studying the representation of the disorder in paintings, literature, and movies. Popular music is arguably the most accessible and ubiquitous of the creative art forms, touching most of us on a daily basis. Reviewed here are the ways in which epilepsy and seizures are used in the lyrics of musicians from a wide variety of musical genres, from hip-hop to rhythm and blues. Many of the ancient associations of epilepsy with madness, horror, and lunacy can be found in these lyrics. However, the language of epilepsy has also been appropriated by some musical artists to represent a state of sexual ecstasy and dance euphoria. The references to these states as "epilepsy" or a "seizure" in numerous songs suggest that this shorthand is widely recognized within some subcultures. Although epilepsy has frequently been associated with female sexual availability in other creative art forms, this novel use of the language of epilepsy represents a contemporary departure in the artistic application of epilepsy-related images and associations in the 21st century.
Sajobi, Tolulope T; Wang, Meng; Ferro, Mark A; Brobbey, Anita; Goodwin, Shane; Speechley, Kathy N; Wiebe, Samuel
2017-10-01
The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified
Attitudes towards people with epilepsy in Moscow.
Guekht, Alla; Gersamiya, Anna; Kaimovskiy, Igor; Mizinova, Maria; Yakovlev, Alexander; Shpak, Alexander
2017-05-01
To assess the knowledge and attitudes in Moscow towards people with epilepsy (PWE). Data were collected from 1167 adults, permanent residents of Moscow, who were interviewed. A 10-item questionnaire was used addressing three major domains: familiarity with epilepsy (2 questions), understanding of epilepsy (5 questions), and attitude towards the PWE (3 questions). Results were standardized to the Moscow population. The study population was generally well informed about epilepsy. About 80% "has heard" of epilepsy; however, personal acquaintance with PWE was reported by less than half of the study participants. The level of understanding of the disease and its etiology was quite low. About 60% of the survey participants believed that epilepsy was a type of mental retardation. One-third (34%) of respondents were afraid to stay in the proximity of PWE. Only 38% of the survey participants considered epilepsy to be curable; men significantly less frequently than women. Overall, the level of understanding of epilepsy was proportional to the level of education of respondents. Negative attitudes towards PWE were demonstrated in a significant part of the population. Almost half of the respondents would object to their child playing or studying with a child who has epilepsy and more than half (57%) were against the marriage of their daughter or son to a person with epilepsy. Two-fifths of the respondents ranked epilepsy as the "least preferred" of the six chronic diseases for a colleague. This is the first study on awareness and attitudes to PWE in the adult population of Moscow. The study demonstrated that the general public is familiar with epilepsy, but has a rather low level of understanding of essential aspects of the disease. There is an overall high level of negative attitudes towards PWE in Russia, creating a need for targeted interventions. These results reinforced the importance of public education in reducing the stigma of epilepsy. Copyright © 2017 Elsevier Inc
Thomas, Rhys H; Mullins, Jane M; Waddington, Tracey; Nugent, Kane; Smith, Phil E M
2010-08-01
An epilepsy diagnosis is very verbal, relying on witness history, personal narrative and analysis of how people describe the experience. Occasionally however, non-verbal descriptions of seizures allow us to gain a fuller understanding of this complex disorder. Artists are often inspired by personal experience, so it should be no surprise to find people depicting images of ill health, both their own and people they have observed. Furthermore, an ailment or affliction may influence an artist's portfolio over their lifetime, such as de Kooning's Alzheimer's disease and Monet's glaucoma. Epilepsy (in contrast with cerebrovascular or neurodegenerative disease) may present not just with a loss of function but with unusual super-added experiences such as déjà vu, ecstatic auras or hallucinations. Here we describe some artists who were thought to have had epilepsy, and the way in which their seizures influenced their art. It appears that for some, they have succeeded despite, rather than because of, their epilepsy and that rather than be inspired by their symptoms they were ashamed of them. If there is a common theme, it is in the unwanted psychological harm of some seizures provoking dark, frustrated imagery.
Obtaining genetic testing in pediatric epilepsy.
Ream, Margie A; Patel, Anup D
2015-10-01
The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Caring for transgender patients with epilepsy.
Johnson, Emily L; Kaplan, Peter W
2017-10-01
Approximately 25 million individuals older than age 15 identify as transgender, representing about 0.3-0.9% of the world's population. The aim of this paper is to identify and describe important medical and social considerations facing transgender persons with epilepsy. We performed literature searches on the following terms: transgender AND epilepsy, transgender AND neurology, gender dysphoria AND epilepsy, gender dysphoria AND neurology. We also performed literature searches for common feminizing or masculinizing treatment regimens, and searched for interactions of those treatment regimens with antiepileptic drugs (AEDs) and with seizures. There are multiple bidirectional interactions between AEDs and the commonly used treatments for aligning external sex characteristics with identified gender. The scope of the transgender population with epilepsy remains to be elucidated. Transgender patients with epilepsy face significant social and medical challenges. Interactions between medical gender-affirming treatments and AEDs are common, and management must depend on knowledge of these interactions to provide appropriate treatment. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Academic Achievement and Behavioral Ratings in Children with Absence and Complex Partial Epilepsy.
ERIC Educational Resources Information Center
Williams, Jane; And Others
1996-01-01
Assessment of 84 children diagnosed with controlled or uncontrolled complex partial or absence seizures but no documented learning or emotional disorders found no influence of seizure type on achievement test scores or behavioral ratings. A main effect was found for degree of control, with poorly controlled seizures correlating with lower reading…
[Attention deficit hyperactivity disorder and epilepsy in childhood].
Idiazábal-Alecha, M Angeles; Kosno, Magdalena
2012-02-29
Both attention deficit hyperactivity disorder (ADHD) and epilepsy are common disorders in childhood. ADHD and epilepsy can be detrimental to the behavior, learning and social relations of affected children. Children with epilepsy and ADHD tend to be at higher risk of school difficulties compared with children who suffer from epilepsy only. We review the works on the prevalence of ADHD in the epileptic population, the prevalence of epilepsy in children with ADHD, and electroencephalographic abnormalities observed in patients with ADHD. The prevalence of ADHD in childhood epilepsy is higher than in the general population and as is the rate of epilepsy in ADHD. Further studies are required to assess the bidirectional relationship between ADHD and epilepsy and the impact of electroencephalographic abnormalities in the clinical course of these patients.
Neurocysticercosis as an infectious acquired epilepsy worldwide.
Reddy, Doodipala Samba; Volkmer, Randy
2017-11-01
Aside from brain injury and genetic causes, there is emerging information on brain infection and inflammation as a common cause of epilepsy. Neurocysticercosis (NCC), the most common cause of epilepsy worldwide, is caused by brain cysts from the Taenia solium tapeworm. In this article, we provide a critical analysis of current and emerging information on the relationship between NCC infection and epilepsy occurrence. We searched PubMed and other databases for reports on the prevalence of NCC and incidence of epilepsy in certain regions worldwide. NCC is caused by brain cysts from the T. solium and related tapeworms. Many people with NCC infection may develop epilepsy but the rates are highly variable. MRI imaging shows many changes including localization of cysts as well as the host response to treatment. Epilepsy, in a subset of NCC patients, appears to be due to hippocampal sclerosis. Serologic and brain imaging profiles are likely diagnostic biomarkers of NCC infection and are also used to monitor the course of treatments. Limited access to these tools is a key limitation to identify and treat NCC-related epilepsy in places with high prevalence of this parasite infestation. Overall, NCC is a common infection in many patients with epilepsy worldwide. Additional clinical and animal studies could confirm common pathology of NCC as a postinfectious epilepsy that is curable. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
EPILEPSY SURGERY IN DRUG RESISTANT TEMPORAL LOBE EPILEPSY ASSOCIATED WITH NEURONAL ANTIBODIES
Carreño, Mar; Bien, Christian; Asadi-Pooya, Ali A.; Sperling, Michael; Marusic, Petr.; Elisak, Martin; Pimentel, Jose; Wehner, Tim; Mohanraj, Rajiv; Uranga, Juan; Gómez-Ibáñez, Asier; Villanueva, Vicente; Gil, Francisco; Donaire, Antonio; Bargalló, Nuria; Rumià, Jordi; Roldán, Pedro; Setoain, Xavier; Pintor, Luis; Boget, Teresa; Bailles, Eva; Falip, Mercè; Aparicio, Javier; Dalmau, Josep; Graus, Francesc
2017-01-01
We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel`s classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients. PMID:28043058
Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies.
Carreño, Mar; Bien, Christian G; Asadi-Pooya, Ali A; Sperling, Michael; Marusic, Petr; Elisak, Martin; Pimentel, Jose; Wehner, Tim; Mohanraj, Rajiv; Uranga, Juan; Gómez-Ibáñez, Asier; Villanueva, Vicente; Gil, Francisco; Donaire, Antonio; Bargalló, Nuria; Rumià, Jordi; Roldán, Pedro; Setoain, Xavier; Pintor, Luis; Boget, Teresa; Bailles, Eva; Falip, Mercè; Aparicio, Javier; Dalmau, Josep; Graus, Francesc
2017-01-01
We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Bidirectional control of absence seizures by the basal ganglia: a computational evidence.
Chen, Mingming; Guo, Daqing; Wang, Tiebin; Jing, Wei; Xia, Yang; Xu, Peng; Luo, Cheng; Valdes-Sosa, Pedro A; Yao, Dezhong
2014-03-01
Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge-basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder.
Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence
Wang, Tiebin; Jing, Wei; Xia, Yang; Xu, Peng; Luo, Cheng; Valdes-Sosa, Pedro A.; Yao, Dezhong
2014-01-01
Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. PMID:24626189
Epilepsy Workshop for Public School Personnel.
ERIC Educational Resources Information Center
Rassel, Gary; And Others
1981-01-01
Epilepsy is one of the most misunderstood and stigmatized disorders in society. A four-hour workshop was conducted over two days with the first two hours discussing types of epilepsy, causes, treatment, and medication. The second part of the study focused on social and psychological implications of epilepsy. (JN)
Shain, Catherine; Ramgopal, Sriram; Fallil, Zianka; Parulkar, Isha; Alongi, Richard; Knowlton, Robert; Poduri, Annapurna
2013-01-01
Purpose Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy. Methods Participants were recruited through the Epilepsy Phenome/Genome Project, a multi-center collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG. Key Findings We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month-37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the focal, unilateral and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement. Significance Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset. PMID:23750890
The interictal language profile in adult epilepsy.
Bartha-Doering, Lisa; Trinka, Eugen
2014-10-01
The purpose of this study was to systematically review the literature on the interictal language profile in adult patients with epilepsy. An extensive literature search was performed using MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, PASCAL, and PSYNDEXplus databases. Key aspects of inclusion criteria were adult patients with epilepsy, patient number >10, and in-depth qualitative investigations of a specific language modality or administration of tests of at least two different language modalities, including comprehension, naming, repetition, reading, writing, and spontaneous speech. Our search strategy yielded 933 articles on epilepsy and language. Of these, 31 met final eligibility criteria. Most included articles focused on temporal lobe epilepsy; only three studies were interested in the language profile of patients with idiopathic generalized epilepsies, and one study on frontal lobe epilepsy met inclusion criteria. Study results showed a pronounced heterogeneity of language abilities in patients with epilepsy, varying from intact language profiles to impairment in several language functions. However, at least 17% of patients displayed deficits in more than one language function, with naming, reading comprehension, spontaneous speech, and discourse production being most often affected. This review underscores the need to evaluate different language functions-including spontaneous speech, discourse abilities, naming, auditory and reading comprehension, reading, writing, and repetition-individually in order to obtain a reliable profile of language functioning in patients with epilepsy. Moreover, our findings show that in contrast to the huge scientific interest of memory functions in epilepsy, the examination of language functions so far played a minor role in epilepsy research, emphasizing the need for future research activities in this field. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials.
DeGiorgio, Christopher M; Taha, Ameer Y
2016-10-01
There is growing interest in alternative and nutritional therapies for drug resistant epilepsy. ῳ-3 fatty acids such as fish or krill oil are widely available supplements used to lower triglycerides and enhance cardiovascular health. ῳ-3 fatty acids have been studied extensively in animal models of epilepsy. Yet, evidence from randomized controlled clinical trials in epilepsy is at an early stage. This report focuses on the key ῳ-3 fatty acids DHA and EPA, their incorporation into the lipid bilayer, modulation of ion channels, and mechanisms of action in reducing excitability within the central nervous system. This paper presents pre-clinical evidence from mouse, rat, and canine models, and reports the efficacy of n-3 fatty acids in randomized controlled clinical trials. An English language search of PubMed and Google scholar for the years 1981-2016 was performed for animal studies and human randomized controlled clinical trials. Expert commentary: Basic science and animal models provide a cogent rationale and substantial evidence for a role of ῳ-3 fatty acids in reducing seizures. Results in humans are limited. Recent Phase II RCT evidence suggests that low to moderate dose of ῳ-3 fatty acids reduce seizures; however, larger multicenter randomized trials are needed to confirm or refute the evidence. The safety, health effects, low cost and ease of use make ῳ-3 fatty acids an intriguing alternative therapy for drug resistant epilepsy. Though safety of profile is excellent, the human data is not yet sufficient to support efficacy in drug resistant epilepsy at this time.
Işler, Ayşegül; Turan, Fatma Dilek; Gözüm, Sebahat; Oncel, Selma
2014-03-01
The aim of this study was to determine the complementary and alternative approaches used by parents of children with epilepsy on epilepsy management. This descriptive study included a total of 304 parents of children with epilepsy aged between 0 and 18years evaluated at the Pediatric Neurology Clinic of Akdeniz University Hospital in Turkey between January and May 2013. Data were collected by using a questionnaire developed by the researchers. It was determined that all the parents use complementary and alternative approaches for their children with epilepsy, and the most common approaches are praying (99.3%); keeping their children away from the effects of smoking (79.8%); feeding their children walnuts (79.6%), butter (59.2%), and bone marrow (58.6%); providing their children with good quality sleep (58.6%); and enabling their children to play games (51%). The approaches commonly applied during seizures include praying (96.2%), comforting their children in their arms and showing affection (55.6%), waiting for seizures to finish at home (45.7%), and laying children on their side (41.1%). Of parents, 98% stated that alternative approaches enable them to control their child's seizures, 100% said that alternative approaches have no adverse effect, and 98.4% stated that they will continue to use these approaches. The children's approaches to cope with epilepsy included looking after pets (72.7%), listening to music (70.1%), watching television (64.5%), playing games (55.3%), praying (51%), and spending time with friends (48.7%). Most of the approaches used by parents and children with epilepsy for the management of illness are determined to consist of complementary approaches that may contribute to management of epilepsy. Knowing the approaches of parents and children with epilepsy that could adversely affect disease management is important for educating parents and children to avoid these potentially harmful interventions. Copyright © 2013 Elsevier Inc. All rights
Upadhya, Dinesh; Hattiangady, Bharathi; Shetty, Geetha A.; Zanirati, Gabriele; Kodali, Maheedhar; Shetty, Ashok K.
2016-01-01
Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. PMID:27532817
Andrade, Danielle M; Bassett, Anne S; Bercovici, Eduard; Borlot, Felippe; Bui, Esther; Camfield, Peter; Clozza, Guida Quaglia; Cohen, Eyal; Gofine, Timothy; Graves, Lisa; Greenaway, Jon; Guttman, Beverly; Guttman-Slater, Maya; Hassan, Ayman; Henze, Megan; Kaufman, Miriam; Lawless, Bernard; Lee, Hannah; Lindzon, Lezlee; Lomax, Lysa Boissé; McAndrews, Mary Pat; Menna-Dack, Dolly; Minassian, Berge A; Mulligan, Janice; Nabbout, Rima; Nejm, Tracy; Secco, Mary; Sellers, Laurene; Shapiro, Michelle; Slegr, Marie; Smith, Rosie; Szatmari, Peter; Tao, Leeping; Vogt, Anastasia; Whiting, Sharon; Carter Snead, O
2017-09-01
The transition from a pediatric to adult health care system is challenging for many youths with epilepsy and their families. Recently, the Ministry of Health and Long-Term Care of the Province of Ontario, Canada, created a transition working group (TWG) to develop recommendations for the transition process for patients with epilepsy in the Province of Ontario. Herein we present an executive summary of this work. The TWG was composed of a multidisciplinary group of pediatric and adult epileptologists, psychiatrists, and family doctors from academia and from the community; neurologists from the community; nurses and social workers from pediatric and adult epilepsy programs; adolescent medicine physician specialists; a team of physicians, nurses, and social workers dedicated to patients with complex care needs; a lawyer; an occupational therapist; representatives from community epilepsy agencies; patients with epilepsy; parents of patients with epilepsy and severe intellectual disability; and project managers. Three main areas were addressed: (1) Diagnosis and Management of Seizures; 2) Mental Health and Psychosocial Needs; and 3) Financial, Community, and Legal Supports. Although there are no systematic studies on the outcomes of transition programs, the impressions of the TWG are as follows. Teenagers at risk of poor transition should be identified early. The care coordination between pediatric and adult neurologists and other specialists should begin before the actual transfer. The transition period is the ideal time to rethink the diagnosis and repeat diagnostic testing where indicated (particularly genetic testing, which now can uncover more etiologies than when patients were initially evaluated many years ago). Some screening tests should be repeated after the move to the adult system. The seven steps proposed herein may facilitate transition, thereby promoting uninterrupted and adequate care for youth with epilepsy leaving the pediatric system. Wiley
Nieto-Rostro, M.; Sandhu, G.; Bauer, C.S.; Jiruska, P.; Jefferys, J.G.R.; Dolphin, A.C.
2014-01-01
The auxiliary α2δ-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The α2δ-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, α2δ-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of α2δ-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of α2δ-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of α2δ-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganization of α2δ-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining. PMID:24641886
Genetics Home Reference: STXBP1 encephalopathy with epilepsy
... Conditions STXBP1 encephalopathy with epilepsy STXBP1 encephalopathy with epilepsy Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description STXBP1 encephalopathy with epilepsy is a condition characterized by recurrent seizures (epilepsy), ...
Self-esteem, behavior, and concerns surrounding epilepsy in siblings of children with epilepsy.
Mims, J
1997-04-01
Researchers document the emotional impact of epilepsy on the child with seizures. Minimal data are available examining the effects of epilepsy on the siblings of children with seizures. Twenty children whose siblings had either frequent seizures or infrequent seizures were matched by age, gender, and birth order to control subjects with no chronic illness. These three groups were compared. Self-esteem, behavioral and social functioning, and family stress were measured by the Piers-Harris Self-Concept Scale, Child Behavior Checklist, and Family Inventory of Life Events. The siblings of children with epilepsy completed the Sibling Concern About Seizure Scale to define and measure their concerns surrounding epilepsy. There is no statistical difference in self-esteem or social functioning among the three groups. There is a trend toward increased incidence of externalizing behavior in siblings of children with frequent seizures. Data indicate a trend toward siblings of children with frequent seizures having more concerns about epilepsy than siblings of children with infrequent seizures. There is significantly more stress in families of children with frequent seizures compared to families of children with infrequent seizures and families of children with no chronic illness. Although there were no significant differences in the self-esteem, behavior, socialization, and concerns between the siblings in the family when compared to the control group or to each other, there were trends in the results that may be of clinical significance. These issues, along with the level of family stress, should be considered when coordinating and providing care to families of children with intractable epilepsy.
Cognition and dementia in older patients with epilepsy
Sen, Arjune; Capelli, Valentina
2018-01-01
Abstract With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer’s disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer’s disease share common risk factors. Recent studies in Alzheimer’s disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer’s disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer’s disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer’s disease and cerebrovascular disease raising
Priorities in pediatric epilepsy research
Baca, Christine B.; Loddenkemper, Tobias; Vickrey, Barbara G.; Dlugos, Dennis
2013-01-01
The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care—particularly epilepsy specialty and behavioral health care—and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous. PMID:23966254
Cost of epilepsy: a systematic review.
Strzelczyk, Adam; Reese, Jens Peter; Dodel, Richard; Hamer, Hajo M
2008-01-01
The objective of this review was to overview published cost-of-illness (COI) studies of epilepsy and their methodological approaches. Epilepsy imposes a substantial burden on individuals and society as a whole. The mean prevalence of epilepsy is estimated at 0.52% in Europe, 0.68% in the US, and peaks up to 1.5% in developing countries. Estimation of the economic burden of epilepsy is of pivotal relevance to enable a rational distribution of healthcare resources. This is especially so with the introduction of the newer antiepileptic drugs (AEDs), the marketing of vagal-nerve stimulators and the resurgence of new surgical treatment options, which have the potential to considerably increase the costs of treating epilepsy.A systematic literature review was performed to identify studies that evaluated direct and indirect costs of epilepsy. Using a standardized assessment form, information on the study design, methodological framework and data sources were extracted from each publication and systematically reported. We identified 22 studies worldwide on costs of epilepsy. The majority of the studies reflected the costs of epilepsy in Europe (three studies each for the UK and Italy, one study each for Germany, the Netherlands, Switzerland, France and the EU) and the US (four studies), but studies were also available from India (two), Hong Kong, Oman, Burundi, Chile and Mexico. The studies utilized different frameworks to evaluate costs. All used a bottom-up approach; however, only 12 studies (55%) evaluated direct as well as indirect costs. The range for the mean annual direct costs lay between 40 International Dollar purchasing power parities (PPP-$) in rural Burundi and PPP-$4748 (adjusted to 2006 values) in a German epilepsy centre. Recent studies suggest AEDs are becoming the main contributor to direct costs. The mean indirect costs ranged between 12% and 85% of the total annual costs. Epilepsy is a cost-intensive disorder. A reliable comparison of the different COI
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sander, T.; Schmitz, B.; Janz, D.
1996-02-16
Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conductedmore » in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an {open_quotes}exclusion region{close_quotes} (lod scores below -2) varied from 0.5 cM up to 22 cM on either side of D2OSl9 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence. 50 refs., 1 fig., 1 tab.« less
Surgical Treatment of Epilepsy
Miller, John W.; Hakimian, Shahin
2013-01-01
Purpose of Review: This article outlines indications for neurosurgical treatment of epilepsy, describes the presurgical workup, summarizes surgical approaches, and details expected risks and benefits. Recent Findings: There is class I evidence for the efficacy of temporal lobectomy in treating intractable seizures, and accumulating documentation that successful surgical treatment reverses much of the disability, morbidity, and excess mortality of chronic epilepsy. Summary: Chronic, uncontrolled focal epilepsy causes progressive disability and increased mortality, but these can be reversed with seizure control. Vigorous efforts to stop seizures are warranted. If two well-chosen and tolerated medication trials do not achieve seizure control, an early workup for epilepsy surgery should be arranged. If this workup definitively identifies the brain region from which the seizures arise, and this region can be removed with a low risk of disabling neurologic deficits, neurosurgery will have a much better chance of stopping seizures than further medication trials. PMID:23739107
Temporal Lobe Epilepsy Semiology
Blair, Robert D. G.
2012-01-01
Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone. PMID:22957241
Psychological treatments for epilepsy.
Ramaratnam, S; Baker, G A; Goldstein, L
2003-01-01
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, electroencephalogram (EEG) bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group trial register (11 June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 2, 2003), MEDLINE (on 11 June 2003) and cross references from identified publications. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions
Benson, Ailbhe; O'Toole, Stephanie; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K
2016-09-01
This paper presents the stigma experiences of children with epilepsy (CWE) and their parents and outlines the relationship between CWE's and parents' stigma perceptions, demographic and seizure variables, and epilepsy-related communication within and external to the family. A mixed-method design was employed. In phase one, 33 CWE and 40 parents participated in qualitative interviews. In phase two, 47 CWE and 72 parents completed a cross-sectional survey. CWE and their parents experience felt and enacted stigma via social exclusion, activity restriction, teasing/bullying, internalised negative feelings to epilepsy, concealment of epilepsy and parental stigma-coaching. Higher CWE and parent stigma perceptions were significantly correlated with greater epilepsy concealment from others outside the family and greater negative affect around epilepsy-related communication within the home. As CWE and their parents grapple with epilepsy-related stigma they may inadvertently contribute to the silence encircling epilepsy through diagnosis concealment, stigma-coaching and/or by engaging in limited family dialogue about epilepsy. Healthcare professionals need to be cognisant of broaching the sensitive topic of epilepsy-related stigma during their engagements with families living with epilepsy. Assisting families to appropriately engage in dialogue surrounding epilepsy is likely to improve the psychosocial wellbeing of CWE and their parents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Hermann, B P; Trenerry, M R; Colligan, R C
1996-07-01
We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.
From Classification to Epilepsy Ontology and Informatics
Zhang, Guo-Qiang; Sahoo, Satya S; Lhatoo, Samden D
2012-01-01
Summary The 2010 International League Against Epilepsy (ILAE) classification and terminology commission report proposed a much needed departure from previous classifications to incorporate advances in molecular biology, neuroimaging, and genetics. It proposed an interim classification and defined two key requirements that need to be satisfied. The first is the ability to classify epilepsy in dimensions according to a variety of purposes including clinical research, patient care, and drug discovery. The second is the ability of the classification system to evolve with new discoveries. Multi-dimensionality and flexibility are crucial to the success of any future classification. In addition, a successful classification system must play a central role in the rapidly growing field of epilepsy informatics. An epilepsy ontology, based on classification, will allow information systems to facilitate data-intensive studies and provide a proven route to meeting the two foregoing key requirements. Epilepsy ontology will be a structured terminology system that accommodates proposed and evolving ILAE classifications, the NIH/NINDS Common Data Elements, the ICD systems and explicitly specifies all known relationships between epilepsy concepts in a proper framework. This will aid evidence based epilepsy diagnosis, investigation, treatment and research for a diverse community of clinicians and researchers. Benefits range from systematization of electronic patient records to multi-modal data repositories for research and training manuals for those involved in epilepsy care. Given the complexity, heterogeneity and pace of research advances in the epilepsy domain, such an ontology must be collaboratively developed by key stakeholders in the epilepsy community and experts in knowledge engineering and computer science. PMID:22765502
Illness perception in Chinese adults with epilepsy.
Ji, Haixia; Zhang, Lei; Li, Lunlan; Gong, Guiping; Cao, Zhaolun; Zhang, Jianfeng; Zhou, Nong; Wang, Yu; Tu, Houmian; Wang, Kai
2016-12-01
Epilepsy is among the most common neurological disorders worldwide. Understanding the patient's subjective experience plays an important role in the treatment and rehabilitation of the patient. However, few studies are concerned about the illness perception of Chinese adults with epilepsy. 117 Chinese adults with epilepsy and 87 Chinese adults with chronic liver disease completed the Chinese version of the Revised Illness Perception Questionnaire (CIPQ-R). The Chinese epilepsy patients also completed the Social Support Rating Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ). A comparison about CIPQ-R score between the epilepsy group and chronic liver group was conducted using the independent sample t test. Partial correlation coefficients were calculated among the eight subscales of the CIPQ-R and its associated factors. Results for the CIPQ-R indicated that both the epilepsy patients and the chronic liver disease patients had a moderate belief in their personal control and treatment control over their disorder. Consistent with our hypothesis, patients with epilepsy and those with chronic liver disease perceived their respective disease similarly in terms of timeline and illness coherence. However, epilepsy patients had a higher negative emotional representations level than that we expected when compared to those of the patients suffering from chronic liver disease. Partial correlation analysis in Chinese epilepsy patients showed that the timeline acute/chronic dimension and emotional representations dimension were closely related to the other dimensions of illness perception. Moreover, the illness perception of the patients was significantly associated with social support, coping style, duration of epilepsy, seizure frequency, and the number of antiepileptic drugs. Chinese patients with epilepsy had limited understanding of the illness, and poor belief in personal control and treatment control. They had a negative emotional response to their illness
Melatonin and childhood refractory epilepsy--a pilot study.
Paprocka, Justyna; Dec, Renata; Jamroz, Ewa; Marszał, Elzbieta
2010-09-01
The aim of the study was to assess diurnal melatonin secretion in children with refractory epilepsy (N=74) as compared to children without epileptic seizures (N=37) and to compare melatonin secretion in children with focal and generalized refractory epilepsy. In the study group 4 subgroups were defined: children with focal symptomatic epilepsy, focal cryptogenic epilepsy, generalized symptomatic epilepsy, and generalized cryptogenic epilepsy. Melatonin level was measured every 3 hours using the RIA method. Analysis of diurnal melatonin secretion indicated a lower level of the hormone in patients with refractory epilepsy. The daily rhythm of melatonin secretion in the study group was maintained, with a peak shift of melatonin secretion especially visible in the subgroup with generalized symptomatic refractory epilepsy in the age group between 6 months and 3 years of age. The hypothesis may be formed that a lowered level of melatonin in the study group in relation to the comparison group is the consequence of the natural course of epilepsy or is influenced by antiepileptic drugs.
Epilepsy surgery in context of neurocysticercosis
Singh, Gagandeep; Chowdhary, Ashwani Kumar
2014-01-01
The association between neurocysticercosis (NCC) and epilepsy is well known and NCC is an important risk factor for epileptic seizures in many Taenia solium-endemic regions of the world. However, while the relationship between NCC and epilepsy is well known, the association between NCC and medically refractory (or surgically remediable epilepsy) has received little attention in the past. Our experience and review of the sparse literature available suggests that NCC is causally related to surgically remediable epilepsy albeit uncommonly so and that association derives its underpinnings from several different scenarios: (1) Medically refractory lesional epilepsy, in which seizures arise from the vicinity of the calcified neurocysticercus lesion (CNL), (2) Medically refractory epilepsy with dual pathology type of relationship between the hippocampal sclerosis (HS) and CNL in which both have been unequivocally demonstrated to give rise to independent seizures and (3) Mesial temporal lobe epilepsy due to HS with a distantly-located CNL, which is in itself not epileptogenic. A major point of controversy revolves around whether or not there exists a causal association between the CNL and HS. We believe that an association exists between NCC and HS and the most important factor influencing this association is the location of the CNL. Furthermore, NCC is a risk factor for medically-refractory epilepsy and that this might account for a considerable proportion of the intractable epilepsy population in endemic regions; the association has been largely ignored owing to the lack of availability of presurgical work-up facilities in these regions. Finally, from a clinical standpoint of presurgical evaluation, patients with CNL and HS should be evaluated on a case by case basis owing to disparate settings underlying the association. PMID:24791092
New-onset epilepsy in the elderly.
Vu, Lily Chi; Piccenna, Loretta; Kwan, Patrick; O'Brien, Terence J
2018-06-01
People who are 60 years old and older have the highest incidence of developing new-onset epilepsy. The increase of the ageing population has resulted in a greater number of patients with new-onset epilepsy or at risk of developing the condition. Previously published review articles regarding epilepsy in older patients have had a broad focus, including people who were diagnosed with epilepsy in childhood or in middle age. This review focuses on the causes, treatment, prognosis and psychosocial impact of new-onset epilepsy in people aged 60 years and over. Following a search of the medical electronic databases and relevant references, we identified 22 studies overall that met the inclusion criteria. Only four randomised clinical trials (RCTs) were identified comparing different antiepileptic drug treatments in this population, demonstrating that newer generation antiepileptic drugs, e.g. lamotrigine and levetiracetam, were generally better tolerated. One uncontrolled study provided promising evidence of good outcomes and safety for surgical resection as a treatment for people with uncontrolled seizures. Five studies reported that people 60 years and over with new-onset epilepsy have significant cognitive impairments, e.g. memory, and psychological issues including depression, anxiety and fatigue. We found that there is very limited evidence to guide treatment in people with Alzheimer's disease and epilepsy. The specific features of new-onset epilepsy in this target population significantly influences the choice of treatment. Cognitive and psychiatric screening before treatment may be useful for management. Two studies with proposed guidelines were identified, but no formal clinical practice guidelines exist for this special population to assist with appropriate management. There is a need for more RCTs that investigate effective treatments with limited side effects. More research studies on the psychosocial effects of new onset epilepsy, and long-term outcomes, for
Neurostimulation as a promising epilepsy therapy.
Lin, Yicong; Wang, Yuping
2017-12-01
The revolution in theory, swift technological developments, and invention of new devices have driven tremendous progress in neurostimulation as a third-line treatment for epilepsy. Over the past decades, neurostimulation took its place in the field of epilepsy as an advanced treatment technique and opened up a new world. Numerous animal studies have proven the physical efficacy of stimulation of the brain and peripheral nerves. Based on this optimistic fundamental research, new advanced techniques are being explored in clinical practice. Over the past century, drawing on the benefits brought about by vagus nerve stimulation for the treatment of epilepsy, various new neurostimulation modalities have been developed to control seizures. Clinical studies including case reports, case series, and clinical trials have been booming in the past several years. This article gives a comprehensive review of most of these clinical studies. In addition to highlighting the advantages of neurostimulation for the treatment of epilepsy, concerns with this modality and future development directions are also discussed. The biggest advantage of neurostimulation over pharmacological treatments for epilepsy is the modulation of the epilepsy network by delivering stimuli at a specific target or the "hub." Conversely, however, a lack of knowledge of epilepsy networks and the mechanisms of neurostimulation may hinder further development. Therefore, theoretical research on the mechanism of epileptogenesis and epilepsy networks is needed in the future. Within the multiple modalities of neuromodulation, the final choice should be made after full discussion with a multidisciplinary team at a presurgical conference. Furthermore, the establishment of a neurostimulation system with standardized parameters and rigorous guidelines is another important issue. To achieve this goal, a worldwide collaboration of epilepsy centers is also suggested in the future.
Reduced Language Connectivity in Pediatric Epilepsy
Leigh N., Sepeta; Louise J., Croft; Lauren A., Zimmaro; Elizabeth S., Duke; Virginia K., Terwilliger; Benjamin E., Yerys; Xiaozhen., You; Chandan J., Vaidya; William D., Gaillard; Madison M., Berl
2014-01-01
Objective Functional connectivity (FC) among language regions is decreased in adults with epilepsy compared to controls, but less is known about FC in children with epilepsy. We sought to determine if language FC is reduced in pediatric epilepsy, and examined clinical factors that associate with language FC in this population. Methods We assessed FC during an age-adjusted language task in children with left-hemisphere focal epilepsy (n=19) compared to controls (n=19). Time series data were extracted for three left ROIs and their right homologues: inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and Wernicke's area (WA) using SPM8. Associations between FC and factors such as cognitive performance, language dominance, and epilepsy duration were assessed. Results Children with epilepsy showed decreased interhemispheric connectivity compared to controls, particularly between core left language regions (IFG, WA) and their right hemisphere homologues, as well as decreased intrahemispheric right frontal FC. Increased intrahemispheric FC between left IFG and left WA was a positive predictor of language skills overall, and naming ability in particular. FC of language areas was not affected by language dominance, as the effects remained when only examining study participants with left language dominance. Overall FC did not differ according to duration of epilepsy or age of onset. Significance FC during a language task is reduced in children, similar to findings in adults. In specific, children with left focal epilepsy demonstrated decreased interhemispheric FC in temporal and frontal language connections and decreased intrahemispheric right frontal FC. These differences were present near the onset of epilepsy. Greater FC between left language centers is related to better language ability. Our results highlight that connectivity of language areas has a developmental pattern and is related to cognitive ability. PMID:25516399
Prevalence of epilepsy in rural Kansas.
Ablah, Elizabeth; Hesdorffer, Dale C; Liu, Yi; Paschal, Angelia M; Hawley, Suzanne; Thurman, David; Hauser, W Allen
2014-05-01
To determine the prevalence of active epilepsy in two southeastern rural Kansas counties. Medical records were abstracted from the emergency rooms, out- and inpatient services and clinics of 9 hospitals, from 10 doctors' offices, and 1 nursing home in and surrounding the two counties. Letters were mailed from hospitals and doctors' offices to invite their potentially eligible patients to participate in an interview. Medical record information and the interview, when available, were used for the final determination of active epilepsy, seizure type, etiology, syndrome, age, and gender in consensus conferences. Prevalence of epilepsy was calculated, and capture-recapture methodology, which estimates prevalence based on what is known about the population, was employed to assess active epilepsy in the two counties. This study identified 404 individuals with active prevalent epilepsy who visited at least one of the 20 facilities during the observation period. The overall prevalence of active epilepsy was 7.2 per 1000. The seizure type for 71.3% of prevalent cases was unknown; among the 76 cases with known and classifiable seizure type, 55.3% had focal with secondary generalized seizures. Among the 222 cases with classifiable etiology, 53.1% were idiopathic/cryptogenic. About 75% (n=301) were captured at only one center, 72% (n=75) of the remaining 103 patients were captured at two centers, and 28 patients were identified at three or more centers. The capture-recapture assessment yielded an estimation of 982 prevalent patients. The overall estimated prevalence of epilepsy in the two Kansas counties using capture-recapture was 17 per 1000. The crude prevalence of epilepsy, using medical record survey methods, was similar to, but on the high end, of other total population prevalence studies in the United States. The capture-recapture assessment suggested that epilepsy prevalence might be considerably higher than the crude prevalence. Copyright © 2014 Elsevier B.V. All
Adenosinergic signaling in epilepsy.
Boison, Detlev
2016-05-01
Despite the introduction of at least 20 new antiepileptic drugs (AEDs) into clinical practice over the past decades, about one third of all epilepsies remain refractory to conventional forms of treatment. In addition, currently used AEDs have been developed to suppress neuronal hyperexcitability, but not necessarily to address pathogenic mechanisms involved in epilepsy development or progression (epileptogenesis). For those reasons endogenous seizure control mechanisms of the brain may provide alternative therapeutic opportunities. Adenosine is a well characterized endogenous anticonvulsant and seizure terminator of the brain. Several lines of evidence suggest that endogenous adenosine-mediated seizure control mechanisms fail in chronic epilepsy, whereas therapeutic adenosine augmentation effectively prevents epileptic seizures, even those that are refractory to conventional AEDs. New findings demonstrate that dysregulation of adenosinergic mechanisms are intricately involved in the development of epilepsy and its comorbidities, whereas adenosine-associated epigenetic mechanisms may play a role in epileptogenesis. The first goal of this review is to discuss how maladaptive changes of adenosinergic mechanisms contribute to the expression of seizures (ictogenesis) and the development of epilepsy (epileptogenesis) by focusing on pharmacological (adenosine receptor dependent) and biochemical (adenosine receptor independent) mechanisms as well as on enzymatic and transport based mechanisms that control the availability (homeostasis) of adenosine. The second goal of this review is to highlight innovative adenosine-based opportunities for therapeutic intervention aimed at reconstructing normal adenosine function and signaling for improved seizure control in chronic epilepsy. New findings suggest that transient adenosine augmentation can have lasting epigenetic effects with disease modifying and antiepileptogenic outcome. This article is part of the Special Issue entitled
Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe
2015-01-01
Study Objectives: The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Methods and Results: Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Conclusions: Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. Citation: Baiardi S, Vandi S, Pizza F, Alvisi L, Toscani L, Zambrelli E, Tinuper P, Mayer G, Plazzi G. Narcolepsy type 1 and
Rosenberg, Evan C; Patra, Pabitra H; Whalley, Benjamin J
2017-05-01
The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB 1 R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB 1 R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant
Angamo, Eskedar Ayele; ul Haq, Rizwan; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe; Kovács, Richard
2017-08-23
Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K⁺] O ) were recorded in parallel with tissue pO₂ and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO₂ following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K⁺] O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism.
Angamo, Eskedar Ayele; Haq, Rizwan ul; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe
2017-01-01
Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K+]O) were recorded in parallel with tissue pO2 and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO2 following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K+]O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism. PMID:28832554
Sahoo, Satya S.; Zhang, Guo-Qiang; Lhatoo, Samden D.
2013-01-01
Summary The epilepsy community increasingly recognizes the need for a modern classification system that can also be easily integrated with effective informatics tools. The 2010 reports by the United States President's Council of Advisors on Science and Technology (PCAST) identified informatics as a critical resource to improve quality of patient care, drive clinical research, and reduce the cost of health services. An effective informatics infrastructure for epilepsy, which is underpinned by a formal knowledge model or ontology, can leverage an ever increasing amount of multimodal data to improve (1) clinical decision support, (2) access to information for patients and their families, (3) easier data sharing, and (4) accelerate secondary use of clinical data. Modeling the recommendations of the International League Against Epilepsy (ILAE) classification system in the form of an epilepsy domain ontology is essential for consistent use of terminology in a variety of applications, including electronic health records systems and clinical applications. In this review, we discuss the data management issues in epilepsy and explore the benefits of an ontology-driven informatics infrastructure and its role in adoption of a “data-driven” paradigm in epilepsy research. PMID:23647220
Richard, Annie E; Scheffer, Ingrid E; Wilson, Sarah J
2017-04-01
Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p<0.001), but only reduced ToM in ASD-relatives (p<0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability. Copyright © 2017 Elsevier Ltd. All rights reserved.
Microglia-Neuron Communication in Epilepsy.
Eyo, Ukpong B; Murugan, Madhuvika; Wu, Long-Jun
2017-01-01
Epilepsy has remained a significant social concern and financial burden globally. Current therapeutic strategies are based primarily on neurocentric mechanisms that have not proven successful in at least a third of patients, raising the need for novel alternative and complementary approaches. Recent evidence implicates glial cells and neuroinflammation in the pathogenesis of epilepsy with the promise of targeting these cells to complement existing strategies. Specifically, microglial involvement, as a major inflammatory cell in the epileptic brain, has been poorly studied. In this review, we highlight microglial reaction to experimental seizures, discuss microglial control of neuronal activities, and propose the functions of microglia during acute epileptic phenotypes, delayed neurodegeneration, and aberrant neurogenesis. Future research that would help fill in the current gaps in our knowledge includes epilepsy-induced alterations in basic microglial functions, neuro-microglial interactions during chronic epilepsy, and microglial contribution to developmental seizures. Studying the role of microglia in epilepsy could inform therapies to better alleviate the disease. GLIA 2016;65:5-18. © 2016 Wiley Periodicals, Inc.
Kerr, Mike; Linehan, Christine; Thompson, Rose; Mula, Marco; Gil-Nagal, Antonio; Zuberi, Sameer M; Glynn, Mike
2014-12-01
This White Paper builds on the publication of the International League Against Epilepsy (ILAE) and International Bureau for Epilepsy (IBE) report "Listening for a change-medical and social needs of people with intellectual disability who have epilepsy" (Listening for a change the medical and social needs of people with epilepsy and intellectual disability, ILAE, 2013). The Paper presents an overview of the recommendations of the report, which aim to improve the health and social care of this important population of people with epilepsy worldwide. Actions in four domains are indicated: (1) the development of standards and initiatives that would enhance diagnosis, pathways to investigation, and treatment; (2) the development of guidelines for treatment, specifically best practice in the management of antiepileptic drugs including rescue medication; (3) the development of standards for primary care, multidisciplinary teamwork, and clinical consultations, with emphasis on the need to enhance communication and improve access to information; and (4) the enhancement of links among different stakeholders including medical services, educational establishments, employment services, organizations providing opportunities for social engagement, and family members. The breadth of needs of this population is a challenge to the epilepsy world, spanning all the professional groupings, care providers, and the research modalities in epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
Monaghan, M M; Menegola, M; Vacher, H; Rhodes, K J; Trimmer, J S
2008-10-15
Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.
Parahippocampal epilepsy with subtle dysplasia: A cause of "imaging negative" partial epilepsy.
Pillay, Neelan; Fabinyi, Gavin C A; Myles, Terry S; Fitt, Gregory J; Berkovic, Samuel F; Jackson, Graeme D
2009-12-01
Lesion-negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging-negative frontal or temporal lobe epilepsy. We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T(1)- and T(2)-weighted images with relative preservation of the gray-white matter boundary on T(1)-weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure-free (one has occasional auras only, follow-up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. In patients with lesion-negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.
Epilepsy. NICHCY Disability Fact Sheet #6
ERIC Educational Resources Information Center
National Dissemination Center for Children with Disabilities, 2010
2010-01-01
Epilepsy is a seizure disorder. According to the Epilepsy Foundation of America, a seizure happens when a brief, strong surge of electrical activity affects part or all of the brain. About three million Americans have epilepsy. Of the 200,000 new cases diagnosed each year, nearly 45,000 are children and adolescents. Following a brief story of a…
Left hemisphere predominance of pilocarpine-induced rat epileptiform discharges
2009-01-01
Background The left cerebral hemisphere predominance in human focal epilepsy has been observed in a few studies, however, there is no related systematic study in epileptic animal on hemisphere predominance. The main goal of this paper is to observe if the epileptiform discharges (EDs) of Pilocarpine-induced epileptic rats could present difference between left hemisphere and right hemisphere or not. Methods The electrocorticogram (ECoG) and electrohippocampogram (EHG) from Pilocarpine-induced epileptic rats were recorded and analyzed using Synchronization likelihood (SL) in order to determine the synchronization relation between different brain regions, then visual check and cross-correlation analysis were adopted to evaluate if the EDs were originated more frequently from the left hemisphere than the right hemisphere. Results The data show that the synchronization between left-EHG and right-EHG, left-ECoG and left-EHG, right-ECoG and right-EHG, left-ECoG and right-ECoG, are significantly strengthened after the brain functional state transforms from non-epileptiform discharges to continuous-epileptiform discharges(p < 0.05). When the state transforms from continuous EDs to periodic EDs, the synchronization is significantly weakened between left-ECoG and left-EHG, left-EHG and right-EHG (p < 0.05). Visual check and the time delay (τ) based cross-correlation analysis finds that 10 out of 13 EDs have a left predominance (77%) and 3 out of 13 EDs are right predominance (23%). Conclusion The results suggest that the left hemisphere may be more prone to EDs in the Pilocarpine-induced rat epilepsy model and implicate that the left hemisphere might play an important role in epilepsy states transition. PMID:19948024
Epilepsy Genetics—Past, Present, and Future
Poduri, Annapurna; Lowenstein, Daniel
2014-01-01
Human epilepsy is a common and heterogeneous condition in which genetics play an important etiological role. We begin by reviewing the past history of epilepsy genetics, a field that has traditionally included studies of pedigrees with epilepsy caused by defects in ion channels and neurotransmitters. We highlight important recent discoveries that have expanded the field beyond the realm of channels and neurotransmitters and that have challenged the notion that single genes produce single disorders. Finally, we project toward an exciting future for epilepsy genetics as large-scale collaborative phenotyping studies come face to face with new technologies in genomic medicine. PMID:21277190
Health care resource utilization in patients with active epilepsy.
Kurth, Tobias; Lewis, Barbara E; Walker, Alexander M
2010-05-01
To evaluate health care resource utilization (HRU) in active epilepsy. Thomson-Reuters insurance databases included 14 million persons in 2005-2007. We extracted information for individuals with insurance claims suggestive of epilepsy. Using iterative expert classification, we sorted patients by type of epilepsy. For each type we calculated prevalence and HRU. A distance analysis identified closely similar types, and a principal components analysis revealed dimensions of variation in HRU. The prevalence of active epilepsy was 3.4 per 1,000. Most common diagnoses among 46,847 patients were generalized convulsive epilepsy (33.3%) and complex partial seizures (24.8%). Patients averaged 10 physician visits per year, 24 diagnostic tests/procedures per year, >30 drug dispensings per year, and <1 emergency room (ER) visit per year, the minority of each of these being related to epilepsy. Female patients generally had more HRU, and HRU increased with age. Patients were hospitalized most frequently for disorders other than epilepsy. HRU was similar for most epilepsy types, excepting grand mal status, epilepsia partialis continua, and infantile spasms. The first principal components of HRU variation was nonepilepsy HRU, followed by components of epilepsy-related medications, other epilepsy/emergency care, and epilepsy visits/diagnostic procedures. The prevalence of active epilepsy in the United States is substantially less than the prevalence of any history of recurrent seizure. Nonepilepsy-related HRU dominated HRU in epilepsy patients and was the principal source of variation. There is a core set of epilepsy diagnoses, the HRU patterns of which are indistinguishable, whereas patients with grand mal status, epilepsia partialis continua, and infantile spasms all have distinct patterns. To provide more specific insights into the economic impact of the condition, studies of HRU in epilepsy should make a distinction about epilepsy-related and unrelated care.
Mansouri, Alireza; Alhadid, Kenda; Valiante, Taufik A
2015-09-01
We report sudden unexpected death in epilepsy (SUDEP) following resective epilepsy surgery in two patients who had been documented as seizure free. One patient had been weaned off of anticonvulsants and was leading a normal life. The other patient had discontinued only one anticonvulsant but had recently started working night shifts. Following resective epilepsy surgery, one of the major objectives among patients, caregivers, and the healthcare team is to safely wean patients off anticonvulsant medications. The main concern regarding anticonvulsant withdrawal is seizure recurrence. While SUDEP following surgical resection has been reported, to our knowledge, there have been no confirmed cases in patients who have been seizure free. Considering the patients reported here, and given that there are no concrete guidelines for the safe withdrawal of anticonvulsants following epilepsy surgery, the discontinuation of anticonvulsants should be considered carefully and must be accompanied by close monitoring and counseling of patients regarding activities that lower seizure threshold, even after successful epilepsy surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.
Mortality risks in new-onset childhood epilepsy.
Berg, Anne T; Nickels, Katherine; Wirrell, Elaine C; Geerts, Ada T; Callenbach, Petra M C; Arts, Willem F; Rios, Christina; Camfield, Peter R; Camfield, Carol S
2013-07-01
Estimate the causes and risk of death, specifically seizure related, in children followed from onset of epilepsy and to contrast the risk of seizure-related death with other common causes of death in the population. Mortality experiences from 4 pediatric cohorts of newly diagnosed patients were combined. Causes of death were classified as seizure related (including sudden unexpected death [SUDEP]), natural causes, nonnatural causes, and unknown. Of 2239 subjects followed up for >30 000 person-years, 79 died. Ten subjects with lethal neurometabolic conditions were ultimately excluded. The overall death rate (per 100 000 person-years) was 228; 743 in complicated epilepsy (with associated neurodisability or underlying brain condition) and 36 in uncomplicated epilepsy. Thirteen deaths were seizure-related (10 SUDEP, 3 other), accounting for 19% of all deaths. Seizure-related death rates were 43 overall, 122 for complicated epilepsy, and 14 for uncomplicated epilepsy. Death rates from other natural causes were 159, 561, and 9, respectively. Of 48 deaths from other natural causes, 37 were due to pneumonia or other respiratory complications. Most excess death in young people with epilepsy is not seizure-related. Mortality is significantly higher compared with the general population in children with complicated epilepsy but not uncomplicated epilepsy. The SUDEP rate was similar to or higher than sudden infant death syndrome rates. In uncomplicated epilepsy, sudden and seizure-related death rates were similar to or higher than rates for other common causes of death in young people (eg, accidents, suicides, homicides). Relating the risk of death in epilepsy to familiar risks may facilitate discussions of seizure-related mortality with patients and families.
Current Surgical Options for Patients with Epilepsy.
Rasul, Fahid T; Bal, Jarnail; Pereira, Erlick A; Tisdall, Martin; Themistocleous, Marios; Haliasos, Nikolaos
2017-01-01
Surgery for epilepsy dates back to 1886 and has undergone significant developments. Today it is considered a key treatment modality in patients who are resistant to pharmacological intervention. It improves seizure control, cognition and quality of life. New technologies, advances in surgical technique and progress in scientific research underlie the expansion of surgery in epilepsy treatment. Effectiveness of surgical treatment depends on several factors including the type of epilepsy, the underlying pathology and the localisation of the epileptogenic zone. Timely referral to an experienced epilepsy surgery centre is important to allow the greatest chance of seizure control and to minimise associated morbidity and mortality. Following referral, patients undergo thorough presurgical investigation to evaluate their suitability for surgery. The commonest form of epilepsy treated by surgery is mesial temporal lobe sclerosis and there is Class I evidence for the medium-term efficacy of temporal lobe resection from two randomised control trials. Various other forms of epilepsy are now considered for resective and neuromodulatory surgical intervention due to favourable results. In this article, the authors review the current status of surgical treatment for epilepsy including the presurgical evaluation of patients, surgical techniques and the future directions in epilepsy surgery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Epidemiology of epilepsy in developing countries.
Senanayake, N.; Román, G. C.
1993-01-01
Epilepsy is an important health problem in developing countries, where its prevalence can be up to 57 per 1000 population. This article reviews the epidemiology of epilepsy in developing countries in terms of its incidence, prevalence, seizure type, mortality data, and etiological factors. The prevalence of epilepsy is particularly high in Latin America and in several African countries, notably Liberia, Nigeria, and the United Republic of Tanzania. Parasitic infections, particularly neurocysticercosis, are important etiological factors for epilepsy in many of these countries. Other reasons for the high prevalence include intracranial infections of bacterial or viral origin, perinatal brain damage, head injuries, toxic agents, and hereditary factors. Many of these factors are, however, preventable or modifiable, and the introduction of appropriate measures to achieve this could lead to a substantial decrease in the incidence of epilepsy in developing countries. PMID:8490989
Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep-Wake Physiology.
Thomas, Alexia M; Schwartz, Michael D; Saxe, Michael D; Kilduff, Thomas S
2017-01-01
Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared electroencephalogram (EEG) and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD). Male contactin-associated protein-like 2 (Cntnap2) knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, electromyogram, body temperature, and locomotor activity. Animals were subjected to a test battery for ASD-related behaviors, followed by 24-hr EEG recordings that were analyzed for sleep-wake parameters and subjected to spectral analysis. Cntnap2 KO rats exhibited severe motor seizures, hyperactivity, and increased consolidation of wakefulness and REM sleep. By contrast, Cntnap2 KO mice demonstrated absence seizure-like events, hypoactivity, and wake fragmentation. Although seizures observed in Cntnap2 KO rats were more similar to those in CDFE patients than in KO mice, neither model fully recapitulated the full spectrum of disease symptoms. However, KOs in both species had reduced spectral power in the alpha (9-12 Hz) range during wake, suggesting a conserved EEG biomarker. Deletion of Cntnap2 impacts similar behaviors and EEG measures in rats and mice, but with profound differences in nature and phenotypic severity. These observations highlight the importance of cross-species comparisons to understand conserved gene functions and the limitations of single- species models to provide translational insights relevant to human diseases. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.
Epilepsy and art: Windows into complexity and comorbidities.
Schachter, Steven C
2016-04-01
The views of artists with epilepsy as expressed through their art provide unique opportunities to gain understanding of the experiences of living with epilepsy and related comorbidities. This paper provides a glimpse into art collected from an international group of artists with epilepsy, focusing on ictal and postictal experiences, psychiatric comorbidities, and social aspects of epilepsy. The art serves to enhance understanding among clinicians and neuroscientists of what it means to have epilepsy as well as to reduce misunderstanding and stigma among the public. It may also inspire neuroscientists to further explore the underlying neurological basis to the rich tapestries of ictal, postictal, and interictal experiences of persons with epilepsy. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". Copyright © 2015 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Arshad, Saadia; Winterhalder, Robert; Underwood, Lisa; Kelesidi, Katerina; Chaplin, Eddie; Kravariti, Eugenia; Anagnostopoulos, Dimitrios; Bouras, Nick; McCarthy, Jane; Tsakanikos, Elias
2011-01-01
Although epilepsy is particularly common among people with intellectual disability (ID) it remains unclear whether it is associated with an increased likelihood of co-morbid psychopathology. We therefore investigated rates of mental health problems and other clinical characteristics in patients with ID and epilepsy (N=156) as compared to patients…
Foley, Jeannine; Burnham, Veronica; Tedoldi, Meghan; Danial, Nika N; Yellen, Gary
2018-01-01
Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1 -/- model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1 -/- and Kcna1 -/- Bad -/- double knockout mice to assess survival and seizure severity. We found that Kcna1 -/- Bad -/- mice outlived Kcna1 -/- mice by approximately 2 weeks. Kcna1 -/- Bad -/- mice also spent significantly less time in seizure than Kcna1 -/- mice on P24 and the day of death, showing that BadKO provides seizure resistance in a genetic model of chronic epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Owolabi, Lukman Femi; Shehu, Naziru Muhammad; Owolabi, Shakirah Desola
2014-01-01
Introduction Students living with epilepsy still find themselves confronted with social barriers that prevent them from academic achievements. Objective The aim of this study was to evaluate knowledge and attitudes of school teachers and to determine the factors associated with good knowledge and positive attitude among nursery, primary and secondary school teachers in Kano, Northwestern Nigeria. Methods A 20-item validated semi-structured questionnaire was self-administered to 200 teachers, selected through multistage sampling technique, in Kano, Northwestern Nigeria. Results The respondents comprised 124 (62%) males and 76(38%) females. Their age ranged between 17 and 55 with a median age of 26 years. All the respondents have heard or read about epilepsy, 13% have had students with epilepsy in their classes before, fifty one (25.5%) of them would object to having an epileptic child in their class. To one hundred and seventy one (85.5%) all seizures were convulsive, 81% of them admitted to not havingadequate knowledge of the initial procedure should their student develop epileptic seizure, 60% believed that epileptic student should be separated from non-epileptic students in the classroom and 44.5% of them preferred alternative medicine. Overall, fifty nine (29.5%) teachers had fair to good knowledge about epilepsy. and one hundred and sixty four (82%) had positive attitude to students with epilepsy. Statistically significant association was found between level of education attained by the respondents and good knowledge about epilepsy as well as between female gender and good attitude. However, none of the variables was statistically significant predictor of knowledge or attitude among the respondents. Conclusion There was low level of knowledge and misconceptions about epilepsy but fair attitude towards epileptic students in Northwestern Nigeria. Higher level of education of the teachers was significantly associated with good attitude. PMID:25489360
Owolabi, Lukman Femi; Shehu, Naziru Muhammad; Owolabi, Shakirah Desola
2014-01-01
Students living with epilepsy still find themselves confronted with social barriers that prevent them from academic achievements. The aim of this study was to evaluate knowledge and attitudes of school teachers and to determine the factors associated with good knowledge and positive attitude among nursery, primary and secondary school teachers in Kano, Northwestern Nigeria. A 20-item validated semi-structured questionnaire was self-administered to 200 teachers, selected through multistage sampling technique, in Kano, Northwestern Nigeria. The respondents comprised 124 (62%) males and 76(38%) females. Their age ranged between 17 and 55 with a median age of 26 years. All the respondents have heard or read about epilepsy, 13% have had students with epilepsy in their classes before, fifty one (25.5%) of them would object to having an epileptic child in their class. To one hundred and seventy one (85.5%) all seizures were convulsive, 81% of them admitted to not having adequate knowledge of the initial procedure should their student develop epileptic seizure, 60% believed that epileptic student should be separated from non-epileptic students in the classroom and 44.5% of them preferred alternative medicine. Overall, fifty nine (29.5%) teachers had fair to good knowledge about epilepsy. and one hundred and sixty four (82%) had positive attitude to students with epilepsy. Statistically significant association was found between level of education attained by the respondents and good knowledge about epilepsy as well as between female gender and good attitude. However, none of the variables was statistically significant predictor of knowledge or attitude among the respondents. There was low level of knowledge and misconceptions about epilepsy but fair attitude towards epileptic students in Northwestern Nigeria. Higher level of education of the teachers was significantly associated with good attitude.
Tchekalarova, Jana D; Ivanova, Natasha; Atanasova, Dimitrina; Pechlivanova, Daniela M; Lazarov, Nikolai; Kortenska, Lidia; Mitreva, Rumiana; Lozanov, Valentin; Stoynev, Alexander
2016-08-01
Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT1 receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT1 receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT1 receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT1 receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT1 receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy.
Modi, Avani C; Schmidt, Matthew; Smith, Aimee W; Turnier, Luke; Glaser, Noah; Wade, Shari L
2017-07-01
Youth with epilepsy exhibit significant deficits in executive functioning (EF), yet there are few interventions to improve EF for adolescents. The aims of the current study were to develop an individually-tailored intervention, called Epilepsy Journey, to improve aspects of EF through an iterative, patient-centered process including focus groups and usability testing. Five adolescents and caregivers participated in focus groups. This input was used to develop ten learning modules based on subscales of the Behavioral Rating Inventory of Executive Functions and key issues that may impact EF in adolescents. Six adolescents participated in usability testing and a usability expert conducted a heuristic evaluation. Demographic information, chart reviews and measures of EF were also completed. Focus group participants and their parents reported difficulties with memory, attention, organization, monitoring, initiation, impulsivity, emotional control, sleep, awareness in schools and managing stress. They also identified successful strategies to address memory and organizational difficulties. Usability testing of the resultant Epilepsy Journey modules revealed problems with navigation and identified features that promoted usability, including progress bars and interactive modules. Program modifications were made after each usability trial resulting in a relatively brief, interactive and readily navigable program. Perceived utility was high with all but one participant. Participants rated the content as helpful and indicated they would recommend Epilepsy Journey to others. Feedback from the focus group and usability testing yielded a feasible, acceptable, relevant and user-friendly web-based intervention for adolescents with epilepsy. The Epilepsy Journey program will be further tested in an open pilot with adolescents with epilepsy and associated EF deficits. Copyright © 2017 Elsevier Inc. All rights reserved.
Lua, Pei Lin; Neni, Widiasmoro Selamat
2012-12-01
Telemedicine innovations, including short message service (SMS), have been used to address a range of health concerns in a variety of settings. Practical, safe, and cost-effective, this simple tool can also potentially improve patients' understanding toward their own diseases via knowledge enhancement. This study was designed to develop and assess the feasibility and acceptability of an SMS-based epilepsy educational program for epilepsy patients. This was a prospective randomized interventional study. Epilepsy outpatients from three general hospitals in East Coast Peninsular Malaysia received the SMS-based mobile epilepsy educational system (MEES) for a 3-month period. In total, 51 patients completed the study (median age, 25.0 years; 51.0% female; 92.2% Malay; 56.9% single; education level, 70.6% ≤SPM/Cambridge O-level equivalent; 25.5% supportive workers; monthly income, 58.8% ≤MYR 500.0/USD 158.5). Approximately 86.0% of the patients owned at least a mobile phone. The total cost of SMS delivery was economically affordable (MYR 3.08/USD 0.98 per patient). Overall, 74.0% agreed that MEES was either very or quite useful. It is encouraging that the majority of patients have offered positive comments and favorable opinions specifically toward epilepsy education (94.0%), drug-taking reminder (90.0%), and clinic appointment reminder (88.0%). It was also reported that 88.2% of the participants would recommend MEES to other people with epilepsy. The current study adds to the growing evidence suggesting that a greater investment in telemedicine programs involving SMS would be both feasible and well received by patients and could be a potentially valuable approach to increase access and effectiveness of epilepsy care.
Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.
Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin
2016-11-01
First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.
Rusbridge, Clare; Long, Sam; Jovanovik, Jelena; Milne, Marjorie; Berendt, Mette; Bhatti, Sofie F M; De Risio, Luisa; Farqhuar, Robyn G; Fischer, Andrea; Matiasek, Kaspar; Muñana, Karen; Patterson, Edward E; Pakozdy, Akos; Penderis, Jacques; Platt, Simon; Podell, Michael; Potschka, Heidrun; Stein, Veronika M; Tipold, Andrea; Volk, Holger A
2015-08-28
Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature.There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6-7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed.
Postictal in situ MRS brain lactate in the rat kindling model.
Maton, B M; Najm, I M; Wang, Y; Lüders, H O; Ng, T C
1999-12-10
To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.
Lowenstein, Daniel H
2011-10-01
Daniel H Lowenstein, MD, is the Robert B and Ellinor Aird Professor and Vice-Chairman of Neurology, Director of the Epilepsy Center, and Director of Physician-Scientist Education and Training at the University of California, San Francisco (UCSF). He received his BA in Mathematics from the University of Colorado and MD from Harvard Medical School. He completed his neurology residency training at UCSF. Dr Lowenstein is a clinician-scientist who has studied both basic science and clinical aspects of epilepsy. In recent years, he has been an organizer of a large-scale, international effort to study the complex genetics of epilepsy, known as the Epilepsy Phenome/Genome Project. He has been actively involved in advancing the cause of epilepsy at the national and international level. Dr Lowenstein served as President of the American Epilepsy Society from 2003 to 2004 and the National Institute of Neurological Diseases and Stroke (NINDS) Advisory Council from 2000 to 2004, and has overseen the development of the NINDS Epilepsy Research Benchmarks since their inception in 2000.
Addressing the burden of epilepsy: Many unmet needs.
Beghi, Ettore
2016-05-01
Epilepsy is a heterogeneous clinical condition characterized by recurrent unprovoked seizures, their causes and complications. The incidence, prevalence and mortality of epilepsy vary with age, place and time contributing to a variable extent to the burden of the disease. Diagnostic misclassification may have strong impact on personal and societal reflections of the disease in light of its clinical manifestations and the need for chronic treatment. Epilepsy accounts for a significant proportion of the world's disease burden ranking fourth after tension-type headache, migraine and Alzheimer disease. Among neurological diseases, it accounts for the highest disability-adjusted life year rates both in men and in women. Although epilepsy is self-remitting in up to 50% of cases, variable long-term prognostic patterns can be identified based on the response to the available treatments. Epilepsy carries an overall increased risk of premature mortality with variable estimates across countries. Premature mortality predominates in patients aged less than 50 years, with epilepsies due to structural/metabolic conditions, with generalized tonic-clonic seizures, and seizures not remitting under treatment. Among deaths directly attributable to epilepsy or seizures, included are sudden unexpected death in epilepsy (SUDEP), status epilepticus, accidents, drowning, unintentional injuries, and suicide. Somatic and psychiatric disorders prevail in patients with epilepsy than in people without epilepsy. Asthma, migraine and cerebral tumors tend to occur more frequently in younger adults while cardiovascular disorders, stroke, dementia and meningioma predominate in the elderly. As being a fairly common clinical condition affecting all ages and requiring long-term (sometimes lifelong) treatment, epilepsy carries high health care costs for the society. Direct costs peak in the first year after diagnosis and then vary according to the severity of the disease, the response to treatment, and
[Images of epilepsy in Shakespeare].
Breuer, Horst
2002-01-01
Epilepsy and the "falling sickness" are mentioned three times in Shakespeare, in Julius Caesar, I.ii, Othello, IV.i., and figuratively in King Lear, II.ii. The present article surveys these passages in the context of modern research findings, literary as well as medico-historical. It adds further material from Renaissance texts and concludes that epilepsy is an omnibus term for a variety of symptoms and pathological conditions, and that Shakespeare's idea of epilepsy is closer to popular stereotypes than has hitherto been assumed.
[Mood disorders and epilepsy surgery: A review].
Yrondi, A; Arbus, C; Valton, L; Schmitt, L
2017-04-01
Historically, there is a strong link between depression and epilepsy. Patients with epilepsy are four to five times more likely to develop a depressive syndrome. It seems that the link between epilepsy and depression is bidirectional. There is little data on mood disorders secondary to epilepsy surgery. The goal of epilepsy surgery is to reduce the number and frequency of attacks, which in turn would allow improvements in mood disorders and cognitive impairment. A systematic search of the international literature was performed using the bibliographic search engines PubMed and Embase. The following MESH terms were used: epilepsy surgery AND (depression OR depressive disorder OR mood disorder). We also used the "related articles" of PubMed, bibliography surveys, conference abstracts and Google Scholar to identify additional relevant papers. Of the 130 studies found by the systematic search, 112 are excluded because they did not take into account the mood disorders secondary to epilepsy surgery. Fifteen studies are included in this review of the literature with a case study. Depression is the psychopathological condition that is the most frequently studied. According to several studies, the prevalence of depression is approximately 30% with nearly 70% of cases diagnosed during the first three months following epilepsy surgery. The majority of patients presented depressive symptoms during the first 3 to 12months after epilepsy surgery. In these studies, the risk of developing depression is correlated with the existence of previous depressive elements relative to the epilepsy surgery. A small number of studies reported cases of de novo depression. Studies have shown a correlation between very good to excellent control of epileptic seizures and a persistent improvement of mood disorders. It would seem that depressive symptoms post-surgery are more common when the surgical intervention concerns the temporal lobe and in particular mesial resections. There are only very
Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe
2015-11-15
The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. © 2015 American Academy of Sleep Medicine.
Epilepsy: habilitation and rehabilitation.
Marks, Warren A; Hernandez, Angel; Gabriel, Marsha
2003-06-01
Rehabilitation represents not only a distinct field of medicine, but also a philosophical and practical treatment approach that can be applied to a variety of chronic disorders. Neurology encompasses many chronic disorders, making it ideal for the application of rehabilitation principles in daily practice. Epilepsy offers a unique opportunity to incorporate rehabilitation principles into the management of a complex medical disorder. Epilepsy is an evolving disease process that changes with the maturation of the central nervous system. The rehabilitative model provides the framework for a dynamic treatment plan to meet the changing needs of the child with epilepsy through the social and developmental changes of childhood, adolescence, and adulthood. The development of epilepsy may complicate the recovery from many acute and chronic conditions that affect the central nervous system. The rehabilitation process must address these many aspects of the disease process and its sequelae. This makes neurologists uniquely qualified to manage the rehabilitation team. The impact of the therapeutic milieu on the recovery process may be as important as any specific medical or surgical intervention.
Diagnosing and treating depression in epilepsy.
Elger, Christian E; Johnston, Samantha A; Hoppe, Christian
2017-01-01
At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress ("burden of epilepsy") explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Primer Part 1-The building blocks of epilepsy genetics.
Helbig, Ingo; Heinzen, Erin L; Mefford, Heather C
2016-06-01
This is the first of a two-part primer on the genetics of the epilepsies within the Genetic Literacy Series of the Genetics Commission of the International League Against Epilepsy. In Part 1, we cover the foundations of epilepsy genetics including genetic epidemiology and the range of genetic variants that can affect the risk for developing epilepsy. We discuss various epidemiologic study designs that have been applied to the genetics of the epilepsies including population studies, which provide compelling evidence for a strong genetic contribution in many epilepsies. We discuss genetic risk factors varying in size, frequency, inheritance pattern, effect size, and phenotypic specificity, and provide examples of how genetic risk factors within the various categories increase the risk for epilepsy. We end by highlighting trends in epilepsy genetics including the increasing use of massive parallel sequencing technologies. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Febrile Infection-Related Epilepsy Syndrome (FIRES): An Overview of Treatment and Recent Patents.
Hon, Kam Lun E Lun; Leung, Alexander K C; Torres, Alcy R
2018-05-08
New-onset refractory status epilepticus (NORSE) refers to a clinical presentation in a patient without active epilepsy or other existing relevant neurological disorder, with new onset of refractory status epilepticus in the absence of a clear acute or active structural, metabolic, or toxic cause. Febrile infection-related epilepsy syndrome (FIRES) is a subset of NORSE that requires a febrile infection between 24 hours and 2 weeks prior to the onset of refractory status epilepticus, with or without fever at the onset of status epilepticus, and with no restriction to the age of the patient. The literature on FIRES is scarce. This article reviews the pathophysiology, clinical features, and various treatment modalities in the treatment of FIRES. A Medline/Pubmed search was conducted using Clinical Queries with the key terms "febrile infection-related epilepsy syndrome", "FIRES", "new-onset refractory status epilepticus" and "NORSE". The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "FIRES", "NORSE" and "febrile epilepsy syndrome" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. FIRES almost invariably begins with a mild nonspecific febrile illness in an otherwise healthy individual. Twenty four hours to two weeks later, seizures begin and quickly become very frequent and worsen, becoming status epilepticus. Seizures can be simple motor, complex partial or secondary generalized. The exact etiology is no known. It is possible that the syndrome is caused by an inflammatory or autoimmune mechanism. Seizures in FIRES are notoriously very difficult to treat. Treatment modalities include, among others, various antiepileptic drugs, ketogenic diet, intravenous corticosteroids, intravenous immunoglobulin, and burst-suppression coma. Outcome is poor; most children are left with significant cognitive disability
[Sleep disorders and epilepsy].
Aoki, Ryo; Ito, Hiroshi
2014-05-01
It has been reported that patients with epilepsy often have insomnia and/or daytime sleepiness; the symptomatologic features differ in seizure types. Not only the administration of anti-epileptics, but also inappropriate sleep hygiene cause daytime sleepiness. In subjective assessment of sleepiness, we need to pay attention if it can correctly assess or not. The prevalence of obstructive sleep apnea in patients with epilepsy is approximately 10-30%. Sleep apnea deteriorates the seizure control because of worsen sleep condition by sleep apnea, especially in elderly patients. Some researchers report that continuous positive airway pressure was effective for seizure control. Patients with epilepsy occasionally have REM sleep behavior disorder as comorbidity. Examination using polysomnography is required for differential diagnosis.
Attention deficits in children with epilepsy: Preliminary findings.
Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica
2017-02-01
Attention difficulties are a common clinical complaint among children with epilepsy. We aimed to compare a range of attentional abilities between groups of children with two common epilepsy syndromes, Temporal Lobe Epilepsy (TLE) and Idiopathic Generalized Epilepsy (IGE), and to healthy controls. We also investigated whether epilepsy factors (laterality of seizure focus, epilepsy onset, duration, and severity) were related to attentional abilities. Multiple dimensions of attention (selective, sustained, and divided attention and attentional control) were assessed directly with standardized neuropsychological measures in 101 children aged 6-16years (23 children with TLE, 20 with IGE and 58 healthy controls). Attention was also assessed indirectly, via a parent-report measure. Children with TLE performed worse than children with IGE (p=0.013) and healthy controls (p<0.001) on a test of attentional control, but no between-group differences were apparent on tests of other attentional abilities. Compared to healthy controls, greater attention problems were reported by parents of children with TLE (p=0.006) and IGE (p=0.012). Left-hemisphere seizure focus and greater epilepsy severity were associated with poorer attentional control and sustained-divided attention, respectively, but no other epilepsy factors were associated with attentional abilities. These findings suggest that children with localization-related epilepsy, but not generalized epilepsy, may be at risk of deficits in attentional control. Interventions aimed at improving attentional control may be targeted at children with localization-related epilepsy, particularly those with a left-hemisphere seizure focus, who appear to be particularly susceptible to this type of attentional deficit. Copyright © 2016 Elsevier Inc. All rights reserved.
Epidemiologic study of epilepsy in young Singaporean men.
Kun, L N; Ling, L W; Wah, Y W; Lian, T T
1999-10-01
This survey of 20,542 Singaporean men born in 1974 studied the clinical features of young men diagnosed with epilepsy on preenlistment screening. All male citizens in Singapore are medically screened at age 18 years before enlistment for compulsory military service. Patients suspected to have epilepsy are then referred to government hospitals for further management. We interviewed the patients and their parents and reviewed their hospital records. Eighty-nine patients with epilepsy were identified, indicating a lifetime prevalence of 4.9/1,000 males by age 18 years. The lifetime prevalence of epilepsy among Chinese, Malays, and Indians were 5.2, 2.8, and 6.4/1,000, respectively; these differences were not statistically significant. The mean age of seizure onset was 11.1 years. Generalized seizures (65.2%) were commoner than partial seizures (34.8%); common seizure types included generalized tonic-clonic seizures (52.8%), complex partial seizures with secondary generalization (24.7%), and myoclonic seizures (5.6%). Common epileptic syndromes included temporal lobe epilepsy (16.9%), juvenile myoclonic epilepsy (5.6%), and frontal lobe epilepsy (2.2%). Eighty-four (94.4%) patients sought medical treatment, and seven (7.9%) patients sought additional traditional treatment. Although 70 (78.7%) patients responded to medication, 14 (15.7%) patients remained refractory to treatment. The lifetime prevalence of epilepsy in young Singaporean men was 4.9/1,000. The majority (65.2%) had generalized seizures. Temporal lobe epilepsy was the commonest (16.9%) defined epilepsy syndrome. More patients with epilepsy (94.4%) sought medical treatment, although 15.7% remained refractory to medication.
Dendritic ion channelopathy in acquired epilepsy
Poolos, Nicholas P.; Johnston, Daniel
2012-01-01
Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577
Cendes, Fernando; Theodore, William H.; Brinkmann, Benjamin H.; Sulc, Vlastimil; Cascino, Gregory D.
2017-01-01
Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454
Rosenberg, Evan C; Tsien, Richard W; Whalley, Benjamin J; Devinsky, Orrin
2015-10-01
Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.
Anesthesia-induced epilepsy: causes and treatment.
Zhao, Xiaojuan; Wang, Xuefeng
2014-09-01
Epilepsy is a type of chronic brain disease that results from an abnormally high synchronization of neuronal discharge. The typical clinical features of epilepsy are paroxysms and transient and stereotyped brain dysfunction. Many cases of epileptic seizures occurring during anesthesia have been reportedx. Recently, risk assessment of epileptic seizures during surgery and anesthesia has gained increasing attention. In this review, we systematically summarize the influence of anesthesia on epileptic seizures; the types, durations and frequencies of seizures related to anesthesia; and the epidemiology, prevention, treatment and prognosis of epilepsy. We also explore the possible mechanism of epilepsy and provide guidance for anesthesia during surgeries.
Familial mesial temporal lobe epilepsy maps to chromosome 4q13.2-q21.3.
Hedera, P; Blair, M A; Andermann, E; Andermann, F; D'Agostino, D; Taylor, K A; Chahine, L; Pandolfo, M; Bradford, Y; Haines, J L; Abou-Khalil, B
2007-06-12
To report results of linkage analysis in a large family with autosomal dominant (AD) familial mesial temporal lobe epilepsy (FMTLE). Although FMTLE is a heterogeneous syndrome, one important subgroup is characterized by a relatively benign course, absence of antecedent febrile seizures, and absence of hippocampal sclerosis. These patients have predominantly simple partial seizures (SPS) and infrequent complex partial seizures (CPS), and intense and frequent déjà vu phenomenon may be the only manifestation of this epilepsy syndrome. No linkage has been described in this form of FMTLE. We identified a four-generation kindred with several affected members meeting criteria for FMTLE and enrolled 21 individuals who gave informed consent. Every individual was personally interviewed and examined; EEG and MRI studies were performed on three affected subjects. DNA was extracted from every enrolled individual. We performed a genome-wide search using an 8 cM panel and fine mapping was performed in the regions with a multipoint lod score >1. We sequenced the highest priority candidate genes. Inheritance was consistent with AD mode with reduced penetrance. Eleven individuals were classified as affected with FMTLE and we also identified two living asymptomatic individuals who had affected offspring. Seizure semiologies included predominantly SPS with déjà vu feeling, infrequent CPS, and rare secondarily generalized tonic-clonic seizures. No structural abnormalities, including hippocampal sclerosis, were detected on MRI performed on three individuals. Genetic analysis detected a group of markers with lod score >3 on chromosome 4q13.2-q21.3 spanning a 7 cM region. No ion channel genes are predicted to be localized within this locus. We sequenced all coding exons of sodium bicarbonate cotransporter (SLC4A) gene, which plays an important role in tissue excitability, and cyclin I (CCNI), because of its role in the cell migration and possibility of subtle cortical abnormalities
Psychological treatments for epilepsy.
Ramaratnam, S; Baker, G A; Goldstein, L H
2005-10-19
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group's Specialized Register (July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), and MEDLINE (1966 to March 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. One small study of galvanic skin response biofeedback reported significant reduction in seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety
The experience of living with adult-onset epilepsy.
Kılınç, Stephanie; van Wersch, Anna; Campbell, Carol; Guy, Alison
2017-08-01
The incidence and prevalence of adults diagnosed with epilepsy is higher compared to those diagnosed in childhood, yet the experience of living with adult-onset epilepsy has rarely been examined. Hence, the current study took a phenomenological approach to examining the experience of living with epilepsy following diagnosis in adulthood. Semi-structured interviews were conducted with 39 people from across the UK, diagnosed with epilepsy between the ages of eighteen and sixty, at two points in time, six months apart. Phenomenological analysis identified three central themes: the unpredictability of seizure occurrence; the ripple effect; and re-evaluating the future. Despite the accepted consensus in the epilepsy literature that living and coping with epilepsy becomes more difficult the older a person is diagnosed, the current findings indicated that this is inadequate. Rather, it is more suitable to consider that those living with adult-onset epilepsy have a specific experience of the condition and particular support needs, given that they once lived their lives as people without epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.
Genetic Forms of Epilepsies and other Paroxysmal Disorders
Olson, Heather E.; Poduri, Annapurna; Pearl, Phillip L.
2016-01-01
Genetic mechanisms explain the pathophysiology of many forms of epilepsy and other paroxysmal disorders such as alternating hemiplegia of childhood, familial hemiplegic migraine, and paroxysmal dyskinesias. Epilepsy is a key feature of well-defined genetic syndromes including Tuberous Sclerosis Complex, Rett syndrome, Angelman syndrome, and others. There is an increasing number of singe gene causes or susceptibility factors associated with several epilepsy syndromes, including the early onset epileptic encephalopathies, benign neonatal/infantile seizures, progressive myoclonus epilepsies, genetic generalized and benign focal epilepsies, epileptic aphasias, and familial focal epilepsies. Molecular mechanisms are diverse, and a single gene can be associated with a broad range of phenotypes. Additional features, such as dysmorphisms, head size, movement disorders, and family history may provide clues to a genetic diagnosis. Genetic testing can impact medical care and counseling. We discuss genetic mechanisms of epilepsy and other paroxysmal disorders, tools and indications for genetic testing, known genotype-phenotype associations, the importance of genetic counseling, and a look towards the future of epilepsy genetics. PMID:25192505
Academic Outcomes in Individuals With Childhood-Onset Epilepsy: Mediating Effects of Working Memory.
Danguecan, Ashley N; Smith, Mary Lou
2017-08-01
Academic difficulties are common in children with epilepsy, although little is known about the effect of various seizure-related and cognitive variables. Given that persistent seizures may negatively impact academics, and that working memory is predictive of academic abilities, we examined the effects of recent seizures and working memory on word reading, spelling, and arithmetic in pediatric epilepsy. We hypothesized that persistent seizures would be associated with lower working memory ability, which would in turn result in poorer academic performance. Our sample consisted of 91 children with epilepsy being treated at the Hospital for Sick Children in Toronto, Canada, who underwent neuropsychological testing between 2002 and 2009 to help determine surgical candidacy. Four to 11 years later, follow-up testing was conducted on both surgical (n=61) and non-surgical (n=30) patients. Seizure status was defined by the presence or absence of seizures within the preceding 12 months. 5000 bias-corrected bootstrap resamples with replacement were used to calculate the 95% confidence intervals (CIs) for the indirect effect of seizure status on academics through working memory, controlling for baseline academic functioning. Persistent seizures were associated with reduced working memory, which was in turn associated with lower reading (B=-4.64, 95% CI [-10.21, -1.30]), spelling (B=-7.09, 95% CI [-13.97, -2.56], and arithmetic scores (B=-8.04, 95% CI [-13.66, -3.58] at follow-up. For children with intractable epilepsy, working memory deficits present a significant barrier to the development of academic skills. Working memory interventions may be a helpful adjunct to academic remediation in this population to facilitate academic progress. (JINS, 2017, 23, 594-604).
Diagnosis of Epilepsy and Related Episodic Disorders.
St Louis, Erik K; Cascino, Gregory D
2016-02-01
This review identifies the diverse and variable clinical presentations associated with epilepsy that may create challenges in diagnosis and treatment. Epilepsy has recently been redefined as a disease characterized by one or more seizures with a relatively high recurrence risk (ie, 60% or greater likelihood). The implication of this definition for therapy is that antiepileptic drug therapy may be initiated following a first seizure in certain situations.EEG remains the most commonly used study in the evaluation of people with epilepsy. Routine EEG may assist in diagnosis, classification of seizure type(s), identification of treatment, and monitoring the efficacy of therapy. Video-EEG monitoring permits seizure classification, assessment of psychogenic nonepileptic seizures, and evaluation of candidacy for epilepsy surgery. MRI is pivotal in elucidating the etiology of the seizure disorder and in suggesting the localization of seizure onset. This article reviews the new International League Against Epilepsy practical clinical definition for epilepsy and the differential diagnosis of other physiologic paroxysmal spells, including syncope, parasomnias, transient ischemic attacks, and migraine, as well as psychogenic nonepileptic seizures. The initial investigational approaches to new-onset epilepsy are considered, including neuroimaging and neurophysiologic investigations with interictal and ictal video-EEG. Neurologists should maintain a high index of suspicion for epilepsy when children or adults present with a single paroxysmal spell or recurrent episodic events.
Tabatabaei, Sayed Shahaboddin; Delbari, Ahmad; Salman-Roghani, Reza; Shahgholi, Leili; Fadayevatan, Reza; Mokhber, Naghmeh; Lokk, Johan
2013-08-01
The incidences of seizures and epilepsy in the population show a peak after 60 years of age. Due to the lack of reported clinical aspects of seizure and epilepsy in the older patients in our region in Iran, this study was conducted to describe the clinical manifestation, etiology, differential diagnosis, and epilepsy subtypes of epilepsy and seizure. A cross-sectional retrospective study was performed on all consecutively elderly seizure and epilepsy patients, referred to the Epilepsy Association in the city of Qom, Iran over a 10-year period. A total of 466 patients aged >60 years were admitted. 31 % of the patients had epilepsy or seizure and 69 % of them had non-epileptic events. The most prevalent differential diagnoses in the beginning were syncope and cardiovascular disorders. The most frequent clinical symptom of epilepsy was generalized tonic-clonic seizures (75 %). The most common cause of seizure was systemic metabolic disorder (27 %). In epileptic elderly patients, no cause was ascertained for 38 % and the most frequently observed pathological factors were cerebrovascular diseases, which accounted for 24 %. The most common type of epileptic seizure was generalized epileptic seizures (75 %). 10 % of elderly epileptic patients suffered from status epilepticus, which was primarily caused by anoxia. Despite the rising rate and potentially profound physical and psychosocial effects of seizures and epilepsy, these disorders have received surprisingly little research focus and attention in Iran. Referring older patients to a specialist or a specialist epilepsy center allows speedy assessment, appropriate investigation and treatment, and less likely to miss the diagnosis.
Psychosocial factors associated with stigma in adults with epilepsy.
Smith, Gigi; Ferguson, Pamela L; Saunders, Lee L; Wagner, Janelle L; Wannamaker, Braxton B; Selassie, Anbesaw W
2009-11-01
Living Well with Epilepsy II called for further attention to stigma and its impact on people with epilepsy. In response, the South Carolina Health Outcomes Project on Epilepsy (SC HOPE) is examining the relationship between socioeconomic status, epilepsy severity, health care utilization, and quality of life in persons diagnosed with epilepsy. The current analysis quantifies perceived stigma reported by adults with epilepsy in relation to demographic, seizure-related, health, and psychosocial factors. It was found that reported levels of stigma were associated with interactions of seizure worry and employment status, self-efficacy and social support, and quality care and age at seizure onset. This information may be used to target and develop evidence-based interventions for adults with epilepsy at high risk for perceived stigma, as well as to inform epilepsy research in self-management.
Family and sexual life in people with epilepsy.
Mameniškienė, Rūta; Guk, Jevgenija; Jatužis, Dalius
2017-01-01
Having epilepsy is much more than having seizures. Epilepsy can have a severe negative effect on quality of life, affecting social relationships, academic achievement, housing, employment, and the ability to live and function independently. We undertook a cross-sectional study in a tertiary epilepsy center in Lithuania, aiming to assess the influence of epilepsy and aspects relating to epilepsy (employment, stigma, anxiety) on patients and their families, and to estimate their quality of family life and sexual functioning. We asked patients to complete a questionnaire about their socio-demographic situation, their seizure types and antiepileptic medications, and their quality of family and sexual life. Our results confirmed that epilepsy seriously influences family life. One third of our patients are lonely and half are childless. Epilepsy leads to difficulty in finding a job, especially for men, and unemployment affects their status in the family. People with epilepsy are uncomfortable interacting with those of the opposite sex and tend to conceal their medical condition from their partner. One third have sexual dysfunction, yet only a quarter of them seek professional help. There is a clear need to improve self-confidence and to reduce social stigma in people with epilepsy, and to encourage them to discuss their problems with specialists. Copyright © 2016 Elsevier Inc. All rights reserved.
Physical activity and epilepsy: proven and predicted benefits.
Arida, Ricardo M; Cavalheiro, Esper A; da Silva, Antonio C; Scorza, Fulvio A
2008-01-01
Epilepsy is a common disease found in 2% of the population, affecting people from all ages. Unfortunately, persons with epilepsy have previously been discouraged from participation in physical activity and sports for fear of inducing seizures or increasing seizure frequency. Despite a shift in medical recommendations toward encouraging rather than restricting participation, the stigma remains and persons with epilepsy continue to be less active than the general population. For this purpose, clinical and experimental studies have analysed the effect of physical exercise on epilepsy. Although there are rare cases of exercise-induced seizures, studies have shown that physical activity can decrease seizure frequency, as well as lead to improved cardiovascular and psychological health in people with epilepsy. The majority of physical activities or sports are safe for people with epilepsy to participate in with special attention to adequate seizure control, close monitoring of medications, and preparation of family or trainers. The evidence shows that patients with good seizure control can participate in both contact and non-contact sports without harmfully affecting seizure frequency. This article reviews the risks and benefits of physical activity in people with epilepsy, discusses sports in which persons with epilepsy may participate, and describes the positive effect of physical exercise in experimental models of epilepsy.
Sherman, Elisabeth M S; Brooks, Brian L; Fay-McClymont, Taryn B; MacAllister, William S
2012-06-01
The Wechsler Intelligence Scale for Children - Fourth Edition is the most widely used intelligence quotient (IQ) test in use today. However, despite numerous studies on IQ in childhood epilepsy, data exist almost exclusively from prior editions of the test, and no studies to date provide information on the sensitivity of specific WISC-IV scores (full-scale IQ [FSIQ], index, and subtest scores) to epilepsy-related cognitive impairments. The goal of this study was to determine the relative sensitivity of WISC-IV index and subscale scores in detecting cognitive problems in a group of clinically referred children with epilepsy compared to matched controls, and to define the relationship among WISC-IV scales, demographic factors, and epilepsy-related variables. WISC-IV data for children with epilepsy and high seizure burden were obtained from the Alberta Children's Hospital (ACH) and the New York University Comprehensive Epilepsy Center (NYU), two tertiary care medical centers for pediatric epilepsy. All children were clinically referred and received a standard assessment including WISC-IV. Matched controls were obtained from the WISC-IV Canadian and American standardization samples. WISC-IV scores from 212 children were included: 106 children with epilepsy (46 girls, 60 boys; mean age 11.0 years, standard deviation [SD] 3.1; parental education 14.5 years, SD 2.8), and 106 controls matched for age, gender, ethnicity, and parental education. Of the children with epilepsy, 44 had a clearly lateralized focus on electroencephalography (EEG) involving either the right or left hemisphere (26 left, 18 right). FSIQ for the epilepsy group was significantly lower than for controls, and 36.8% of children had IQs compatible with intellectual disability (FSIQ < 70), versus <1% of controls. In children with epilepsy, Working Memory and Processing Speed Index scores were lower than those for Verbal Comprehension and Perceptual Reasoning (p < 0.01). At the subtest level, scores for
Ali, Amza
2018-04-01
Epilepsy is a frequently misunderstood and highly stigmatized condition. Major treatment gaps exist across the world, most so in areas of financial constraint. Classification permits the best approaches to treatment and to ascertaining prognosis. The International League Against Epilepsy's new classification system emphasizes clinical aspects and utilizes all available resources to determine whether it is a focal or generalized epilepsy. The most important tools are a careful history, clinical examination, electroencephalography, and appropriate neuroimaging. Inadequate, delayed, and incomplete evaluation may lead to misdiagnosis and costly mismanagement. Treatment is generally pharmacological, with approximately 20 to 30% of patients eventually proving refractory to medications and thus becoming potential surgical candidates. The type of epilepsy, age, gender, comorbidities, drug interactions, and drug cost are important factors in choosing an antiepileptic drug (AED). The teratogenic potential of some AEDs, weight gain, and menstrual hormone-related issues are important considerations in women. The impact of AEDs on bone health is critical in all age groups, particularly in the elderly. Psychiatric problems, mostly depression and anxiety, can have a great impact on seizure control and overall quality of life. Finally, effective partnerships and collaborations can bring resources, both human and financial, to regions that would otherwise find it impossible to effect change on their own. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Rosenberg, Evan C.; Patra, Pabitra H.; Whalley, Benjamin J.
2017-01-01
The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB1R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB1R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant
Mathew, Jobin; Balakrishnan, Savitha; Antony, Sherin; Abraham, Pretty Mary; Paulose, C S
2012-02-24
Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.
Healthcare utilization and costs in adults with stable and uncontrolled epilepsy.
Cramer, Joyce A; Wang, Zhixiao J; Chang, Eunice; Powers, Annette; Copher, Ronda; Cherepanov, Dasha; Broder, Michael S
2014-02-01
Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p<.02). A greater proportion of patients with uncontrolled epilepsy had ≥1 hospitalization or emergency department visit (p<.001). Patients with uncontrolled epilepsy had a greater mean length of hospital stay and more physician office visits (p<.034). After adjustment, the odds of hospitalization (OR: 1.8, any diagnosis; 2.2, epilepsy-related) and emergency department visit (OR: 1.6, any diagnosis; 1.9, epilepsy-related) were greater for patients with uncontrolled epilepsy. Annual overall ($23,238 vs. $13,839) and epilepsy-related ($12,399 vs. $5511) costs were higher in patients with uncontrolled epilepsy and remained higher after adjustment (p<.001). Patients with uncontrolled epilepsy use more services and incur higher costs compared with those with stable epilepsy. Epilepsy-related costs accounted for <50% of the total costs, suggesting that comorbid conditions and
Neni, Widiasmoro Selamat
2012-01-01
Abstract Background: Telemedicine innovations, including short message service (SMS), have been used to address a range of health concerns in a variety of settings. Practical, safe, and cost-effective, this simple tool can also potentially improve patients' understanding toward their own diseases via knowledge enhancement. This study was designed to develop and assess the feasibility and acceptability of an SMS-based epilepsy educational program for epilepsy patients. Subjects and Methods: This was a prospective randomized interventional study. Epilepsy outpatients from three general hospitals in East Coast Peninsular Malaysia received the SMS-based mobile epilepsy educational system (MEES) for a 3-month period. Results: In total, 51 patients completed the study (median age, 25.0 years; 51.0% female; 92.2% Malay; 56.9% single; education level, 70.6% ≤SPM/Cambridge O-level equivalent; 25.5% supportive workers; monthly income, 58.8% ≤MYR 500.0/USD 158.5). Approximately 86.0% of the patients owned at least a mobile phone. The total cost of SMS delivery was economically affordable (MYR 3.08/USD 0.98 per patient). Overall, 74.0% agreed that MEES was either very or quite useful. It is encouraging that the majority of patients have offered positive comments and favorable opinions specifically toward epilepsy education (94.0%), drug-taking reminder (90.0%), and clinic appointment reminder (88.0%). It was also reported that 88.2% of the participants would recommend MEES to other people with epilepsy. Conclusions: The current study adds to the growing evidence suggesting that a greater investment in telemedicine programs involving SMS would be both feasible and well received by patients and could be a potentially valuable approach to increase access and effectiveness of epilepsy care. PMID:23078181