Concepts of Connectivity and Human Epileptic Activity

PubMed Central

Lemieux, Louis; Daunizeau, Jean; Walker, Matthew C.

2011-01-01

This review attempts to place the concept of connectivity from increasingly sophisticated neuroimaging data analysis methodologies within the field of epilepsy research. We introduce the more principled connectivity terminology developed recently in neuroimaging and review some of the key concepts related to the characterization of propagation of epileptic activity using what may be called traditional correlation-based studies based on EEG. We then show how essentially similar methodologies, and more recently models addressing causality, have been used to characterize whole-brain and regional networks using functional MRI data. Following a discussion of our current understanding of the neuronal system aspects of the onset and propagation of epileptic discharges and seizures, we discuss the most advanced and ambitious framework to attempt to fully characterize epileptic networks based on neuroimaging data. PMID:21472027

Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits.

PubMed

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; De Maria, Michela; Migliore, Michele; Migliore, Rosanna; Taglialatela, Maurizio

2015-03-04

Mutations in Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3) genes, encoding for voltage-gated K(+) channel subunits underlying the neuronal M-current, have been associated with a wide spectrum of early-onset epileptic disorders ranging from benign familial neonatal seizures to severe epileptic encephalopathies. The aim of the present work has been to investigate the molecular mechanisms of channel dysfunction caused by voltage-sensing domain mutations in Kv7.2 (R144Q, R201C, and R201H) or Kv7.3 (R230C) recently found in patients with epileptic encephalopathies and/or intellectual disability. Electrophysiological studies in mammalian cells transfected with human Kv7.2 and/or Kv7.3 cDNAs revealed that each of these four mutations stabilized the activated state of the channel, thereby producing gain-of-function effects, which are opposite to the loss-of-function effects produced by previously found mutations. Multistate structural modeling revealed that the R201 residue in Kv7.2, corresponding to R230 in Kv7.3, stabilized the resting and nearby voltage-sensing domain states by forming an intricate network of electrostatic interactions with neighboring negatively charged residues, a result also confirmed by disulfide trapping experiments. Using a realistic model of a feedforward inhibitory microcircuit in the hippocampal CA1 region, an increased excitability of pyramidal neurons was found upon incorporation of the experimentally defined parameters for mutant M-current, suggesting that changes in network interactions rather than in intrinsic cell properties may be responsible for the neuronal hyperexcitability by these gain-of-function mutations. Together, the present results suggest that gain-of-function mutations in Kv7.2/3 currents may cause human epilepsy with a severe clinical course, thus revealing a previously unexplored level of complexity in disease pathogenetic mechanisms. Copyright © 2015 the authors 0270-6474/15/353782-12$15.00/0.

De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

PubMed

Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

2014-06-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

Impact of cognitive stimulation on ripples within human epileptic and non-epileptic hippocampus.

PubMed

Brázdil, Milan; Cimbálník, Jan; Roman, Robert; Shaw, Daniel J; Stead, Matt M; Daniel, Pavel; Jurák, Pavel; Halámek, Josef

2015-07-25

Until now there has been no way of distinguishing between physiological and epileptic hippocampal ripples in intracranial recordings. In the present study we addressed this by investigating the effect of cognitive stimulation on interictal high frequency oscillations in the ripple range (80-250 Hz) within epileptic (EH) and non-epileptic hippocampus (NH). We analyzed depth EEG recordings in 10 patients with intractable epilepsy, in whom hippocampal activity was recorded initially during quiet wakefulness and subsequently during a simple cognitive task. Using automated detection of ripples based on amplitude of the power envelope, we analyzed ripple rate (RR) in the cognitive and resting period, within EH and NH. Compared to quiet wakefulness we observed a significant reduction of RR during cognitive stimulation in EH, while it remained statistically marginal in NH. Further, we investigated the direct impact of cognitive stimuli on ripples (i.e. immediately post-stimulus), which showed a transient statistically significant suppression of ripples in the first second after stimuli onset in NH only. Our results point to a differential reactivity of ripples within EH and NH to cognitive stimulation.

Assortative mixing in functional brain networks during epileptic seizures

NASA Astrophysics Data System (ADS)

Bialonski, Stephan; Lehnertz, Klaus

2013-09-01

We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.

Imaging DC MEG Fields Associated with Epileptic Onset

NASA Astrophysics Data System (ADS)

Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

2004-10-01

Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

Global Interactions Analysis of Epileptic ECoG Data

NASA Astrophysics Data System (ADS)

Ortega, Guillermo J.; Sola, Rafael G.; Pastor, Jesús

2007-05-01

Localization of the epileptogenic zone is an important issue in epileptology, even though there is not a unique definition of the epileptic focus. The objective of the present study is to test ultrametric analysis to uncover cortical interactions in human epileptic data. Correlation analysis has been carried out over intraoperative Electro-Corticography (ECoG) data in 2 patients suffering from temporal lobe epilepsy (TLE). Recordings were obtained using a grid of 20 electrodes (5×4) covering the lateral temporal lobe and a strip of either 4 or 8 electrodes at the mesial temporal lobe. Ultrametric analysis was performed in the averaged final correlation matrices. By using the matrix of linear correlation coefficients and the appropriate metric distance between pairs of electrodes time series, we were able to construct Minimum Spanning Trees (MST). The topological connectivity displayed by these trees gives useful and valuable information regarding physiological and pathological information in the temporal lobe of epileptic patients.

Two different mechanisms associated with ripple-like oscillations (100-250 Hz) in the human epileptic subiculum in vitro

PubMed Central

Alvarado-Rojas, C; Huberfeld, G; Baulac, M; Clemenceau, S; Charpier, S; Miles, R; Menendez de la Prida, L; Le Van Quyen, M

2015-01-01

Transient high-frequency oscillations (150-600 Hz) in local field potential generated by human hippocampal and parahippocampal areas have been related to both physiological and pathological processes. The cellular basis and effects of normal and abnormal forms of high-frequency oscillations (HFO) has been controversial. Here, we searched for HFOs in slices of the subiculum prepared from human hippocampal tissue resected for treatment of pharmacoresistant epilepsy. HFOs occurred spontaneously in extracellular field potentials during interictal discharges (IID) and also during pharmacologically induced preictal discharges (PID) preceding ictal-like events. While most of these events might be considered pathological since they invaded the fast ripple band (>250 Hz), others were spectrally similar to physiological ripples (150-250 Hz). Do similar cellular mechanisms underly IID-ripples and PID-ripples? Are ripple-like oscillations a valid proxy of epileptogenesis in human TLE? With combined intra- or juxta-cellular and extracellular recordings, we showed that, despite overlapping spectral components, ripple-like IID and PID oscillations were associated with different cellular and synaptic mechanisms. IID-ripples were associated with rhythmic GABAergic and glutamatergic synaptic potentials with moderate neuronal firing. In contrast, PID-ripples were associated with depolarizing synaptic inputs frequently reaching the threshold for bursting in most cells. Thus ripple-like oscillations (100-250 Hz) in the human epileptic hippocampus are associated with different mechanisms for synchrony reflecting distinct dynamic changes in inhibition and excitation during interictal and pre-ictal states. PMID:25448920

Methods and utility of EEG-fMRI in epilepsy

PubMed Central

Lemieux, Louis; Chaudhary, Umair Javaid

2015-01-01

Brain activity data in general and more specifically in epilepsy can be represented as a matrix that includes measures of electrophysiology, anatomy and behaviour. Each of these sub-matrices has a complex interaction depending upon the brain state i.e., rest, cognition, seizures and interictal periods. This interaction presents significant challenges for interpretation but also potential for developing further insights into individual event types. Successful treatments in epilepsy hinge on unravelling these complexities, and also on the sensitivity and specificity of methods that characterize the nature and localization of underlying physiological and pathological networks. Limitations of pharmacological and surgical treatments call for refinement and elaboration of methods to improve our capability to localise the generators of seizure activity and our understanding of the neurobiology of epilepsy. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI), by potentially circumventing some of the limitations of EEG in terms of sensitivity, can allow the mapping of haemodynamic networks over the entire brain related to specific spontaneous and triggered epileptic events in humans, and thereby provide new localising information. In this work we review the published literature, and discuss the methods and utility of EEG-fMRI in localising the generators of epileptic activity. We draw on our experience and that of other groups, to summarise the spectrum of information provided by an increasing number of EEG-fMRI case-series, case studies and group studies in patients with epilepsy, for its potential role to elucidate epileptic generators and networks. We conclude that EEG-fMRI provides a multidimensional view that contributes valuable clinical information to localize the epileptic focus with potential important implications for the surgical treatment of some patients with drug-resistant epilepsy, and insights into the resting state and cognitive network dynamics. PMID:25853087

The functional organization of human epileptic hippocampus

PubMed Central

Klimes, Petr; Duque, Juliano J.; Brinkmann, Ben; Van Gompel, Jamie; Stead, Matt; St. Louis, Erik K.; Halamek, Josef; Jurak, Pavel

2016-01-01

The function and connectivity of human brain is disrupted in epilepsy. We previously reported that the region of epileptic brain generating focal seizures, i.e., the seizure onset zone (SOZ), is functionally isolated from surrounding brain regions in focal neocortical epilepsy. The modulatory effect of behavioral state on the spatial and spectral scales over which the reduced functional connectivity occurs, however, is unclear. Here we use simultaneous sleep staging from scalp EEG with intracranial EEG recordings from medial temporal lobe to investigate how behavioral state modulates the spatial and spectral scales of local field potential synchrony in focal epileptic hippocampus. The local field spectral power and linear correlation between adjacent electrodes provide measures of neuronal population synchrony at different spatial scales, ∼1 and 10 mm, respectively. Our results show increased connectivity inside the SOZ and low connectivity between electrodes in SOZ and outside the SOZ. During slow-wave sleep, we observed decreased connectivity for ripple and fast ripple frequency bands within the SOZ at the 10 mm spatial scale, while the local synchrony remained high at the 1 mm spatial scale. Further study of these phenomena may prove useful for SOZ localization and help understand seizure generation, and the functional deficits seen in epileptic eloquent cortex. PMID:27030735

Multichannel continuous electroencephalography-functional near-infrared spectroscopy recording of focal seizures and interictal epileptiform discharges in human epilepsy: a review

PubMed Central

Peng, Ke; Pouliot, Philippe; Lesage, Frédéric; Nguyen, Dang Khoa

2016-01-01

Abstract. Functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging technique as it allows noninvasive and long-term monitoring of cortical hemodynamics. Recent work by our group and others has revealed the potential of fNIRS, combined with electroencephalography (EEG), in the context of human epilepsy. Hemodynamic brain responses attributed to epileptic events, such as seizures and interictal epileptiform discharges (IEDs), are routinely observed with a good degree of statistical significance and in concordance with clinical presentation. Recording done with over 100 channels allows sufficiently large coverage of the epileptic focus and other areas. Three types of seizures have been documented: frontal lobe seizures, temporal lobe seizures, and posterior seizures. Increased oxygenation was observed in the epileptic focus in most cases, while rapid but similar hemodynamic variations were identified in the contralateral homologous region. While investigating IEDs, it was shown that their hemodynamic effect is observable with fNIRS, that their response is associated with significant (inhibitive) nonlinearities, and that the sensitivity and specificity of fNIRS to localize the epileptic focus can be estimated in a sample of 40 patients. This paper first reviews recent EEG-fNIRS developments in epilepsy research and then describes applications to the study of focal seizures and IEDs. PMID:26958576

Social behavior impairment in offspring exposed to maternal seizures in utero.

PubMed

Novaes, Gisane Faria; Amado, Debora; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

2012-06-01

Human and animal models have demonstrated that maternal seizures in utero could be deleterious to the development of the offspring. This study focused on the social behavior of offspring exposed to seizures in utero. A pilocarpine model of temporal lobe epilepsy was induced in female Wistar rats that were mated after the first spontaneous seizure. Early after birth, pups from an epileptic mother were reared by a control mother. To evaluate the influence of the adoption process, two other groups were added: rat pups from control mothers cross-fostered with other control mothers, and rat pups reared by their birth mother. Animals exposed to seizures in utero showed impaired social behavior with no signs of anxiety-like behavior. This study demonstrated that epileptic seizures during pregnancy could be harmful to brain development and may increase the risk of developing neurodevelopmental disorders. The mechanisms underlying the abnormalities of social behavior are not well understood, and further studies in this field are warranted.

Genetics of human epilepsies: Continuing progress.

PubMed

Szepetowski, Pierre

2018-03-01

Numerous epilepsy genes have been identified in the last years, mostly in the (rare) monogenic forms and thanks to the increased availability and the decreased cost of next-generation sequencing approaches. Besides the somehow expected group of epilepsy genes encoding various ion channel subunits (e.g. sodium or potassium channel subunits, or GABA receptors, or glutamate-gated NMDA receptors), more diversity has emerged recently, with novel epilepsy genes encoding proteins playing a wide range of physiological roles at the cellular and molecular levels, such as synaptic proteins, members of the mTOR pathway, or proteins involved in chromatin remodeling. The overall picture is somehow complicated: one given epilepsy gene can be associated with more than one epileptic phenotype, and with variable degrees of severity, from the benign to the severe forms (e.g. epileptic encephalopathies), and with various comorbid conditions such as migraine or autism spectrum of disorders. Conversely, one given epileptic syndrome may be associated with different genes, some of which have obvious links with each other (e.g. encoding different subunits of the same receptor) while other ones have no clear relationships. Also genomic copy number variations have been detected, some of which, albeit rare, may confer high risk to epilepsy. Whereas translation from gene identification to targeted medicine still remains challenging, progress in epilepsy genetics is currently revolutionizing genetic-based diagnosis and genetic counseling. Epilepsy gene identification also represents a key entry point to start in deciphering the underlying pathophysiological mechanisms via the design and the study of the most pertinent cellular and animal models - which may in turn provide proofs-of-principle for future applications in human epilepsies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Localisation of epileptic foci using novel imaging modalities

PubMed Central

De Ciantis, Alessio; Lemieux, Louis

2013-01-01

Purpose of review This review examines recent reports on the use of advanced techniques to map the regions and networks involved during focal epileptic seizure generation in humans. Recent findings A number of imaging techniques are capable of providing new localizing information on the ictal processes and epileptogenic zone. Evaluating the clinical utility of these findings has been mainly performed through post-hoc comparison with the findings of invasive EEG and ictal single-photon emission computed tomography, using postsurgical seizure reduction as the main outcome measure. Added value has been demonstrated in MRI-negative cases. Improved understanding of the human ictiogenic processes and the focus vs. network hypothesis is likely to result from the application of multimodal techniques that combine electrophysiological, semiological, and whole-brain coverage of brain activity changes. Summary On the basis of recent research in the field of neuroimaging, several novel imaging modalities have been improved and developed to provide information about the localization of epileptic foci. PMID:23823464

Mapping and mining interictal pathological gamma (30–100 Hz) oscillations with clinical intracranial EEG in patients with epilepsy

PubMed Central

Smart, Otis; Maus, Douglas; Marsh, Eric; Dlugos, Dennis; Litt, Brian; Meador, Kimford

2012-01-01

Localizing an epileptic network is essential for guiding neurosurgery and antiepileptic medical devices as well as elucidating mechanisms that may explain seizure-generation and epilepsy. There is increasing evidence that pathological oscillations may be specific to diseased networks in patients with epilepsy and that these oscillations may be a key biomarker for generating and indentifying epileptic networks. We present a semi-automated method that detects, maps, and mines pathological gamma (30–100 Hz) oscillations (PGOs) in human epileptic brain to possibly localize epileptic networks. We apply the method to standard clinical iEEG (<100 Hz) with interictal PGOs and seizures from six patients with medically refractory epilepsy. We demonstrate that electrodes with consistent PGO discharges do not always coincide with clinically determined seizure onset zone (SOZ) electrodes but at times PGO-dense electrodes include secondary seizure-areas (SS) or even areas without seizures (NS). In 4/5 patients with epilepsy surgery, we observe poor (Engel Class 4) post-surgical outcomes and identify more PGO-activity in SS or NS than in SOZ. Additional studies are needed to further clarify the role of PGOs in epileptic brain. PMID:23105174

Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

NASA Astrophysics Data System (ADS)

Kim, Suhwan; Jung, Unsang; Baek, Juyoung; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-01-01

Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms.

PubMed

Zhang, Yifan; Xu, Jingwei; Zhang, Kun; Yang, Wei; Li, Bingjin

2018-01-01

Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy". As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

PubMed

Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

2018-01-01

Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Predicting novel histopathological microlesions in human epileptic brain through transcriptional clustering.

PubMed

Dachet, Fabien; Bagla, Shruti; Keren-Aviram, Gal; Morton, Andrew; Balan, Karina; Saadat, Laleh; Valyi-Nagy, Tibor; Kupsky, William; Song, Fei; Dratz, Edward; Loeb, Jeffrey A

2015-02-01

Although epilepsy is associated with a variety of abnormalities, exactly why some brain regions produce seizures and others do not is not known. We developed a method to identify cellular changes in human epileptic neocortex using transcriptional clustering. A paired analysis of high and low spiking tissues recorded in vivo from 15 patients predicted 11 cell-specific changes together with their 'cellular interactome'. These predictions were validated histologically revealing millimetre-sized 'microlesions' together with a global increase in vascularity and microglia. Microlesions were easily identified in deeper cortical layers using the neuronal marker NeuN, showed a marked reduction in neuronal processes, and were associated with nearby activation of MAPK/CREB signalling, a marker of epileptic activity, in superficial layers. Microlesions constitute a common, undiscovered layer-specific abnormality of neuronal connectivity in human neocortex that may be responsible for many 'non-lesional' forms of epilepsy. The transcriptional clustering approach used here could be applied more broadly to predict cellular differences in other brain and complex tissue disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus.

PubMed

Foffani, Guglielmo; Uzcategui, Yoryani G; Gal, Beatriz; Menendez de la Prida, Liset

2007-09-20

Ripples are sharp-wave-associated field oscillations (100-300 Hz) recorded in the hippocampus during behavioral immobility and slow-wave sleep. In epileptic rats and humans, a different and faster oscillation (200-600 Hz), termed fast ripples, has been described. However, the basic mechanisms are unknown. Here, we propose that fast ripples emerge from a disorganized ripple pattern caused by unreliable firing in the epileptic hippocampus. Enhanced synaptic activity is responsible for the irregular bursting of CA3 pyramidal cells due to large membrane potential fluctuations. Lower field interactions and a reduced spike-timing reliability concur with decreased spatial synchronization and the emergence of fast ripples. Reducing synaptically driven membrane potential fluctuations improves both spike-timing reliability and spatial synchronization and restores ripples in the epileptic hippocampus. Conversely, a lower spike-timing reliability, with reduced potassium currents, is associated with ripple shuffling in normal hippocampus. Therefore, fast ripples may reflect a pathological desynchronization of the normal ripple pattern.

Multifractal and wavelet analysis of epileptic seizures

NASA Astrophysics Data System (ADS)

Dick, Olga E.; Mochovikova, Irina A.

The aim of the study is to develop quantitative parameters of human electroencephalographic (EEG) recordings with epileptic seizures. We used long-lasting recordings from subjects with epilepsy obtained as part of their clinical investigation. The continuous wavelet transform of the EEG segments and the wavelet-transform modulus maxima method enable us to evaluate the energy spectra of the segments, to fin lines of local maximums, to gain the scaling exponents and to construct the singularity spectra. We have shown that the significant increase of the global energy with respect to background and the redistribution of the energy over the frequency range are observed in the patterns involving the epileptic activity. The singularity spectra expand so that the degree of inhomogenety and multifractality of the patterns enhances. Comparing the results gained for the patterns during different functional probes such as open and closed eyes or hyperventilation we demonstrate the high sensitivity of the analyzed parameters (the maximal global energy, the width and asymmetry of the singularity spectrum) for detecting the epileptic patterns.

Wavelet analysis of epileptic spikes

NASA Astrophysics Data System (ADS)

Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

2003-05-01

Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

Dynamic Imaging of Coherent Sources Reveals Different Network Connectivity Underlying the Generation and Perpetuation of Epileptic Seizures

PubMed Central

Anwar, Abdul Rauf; Deuschl, Günther; Stephani, Ulrich; Raethjen, Jan; Siniatchkin, Michael

2013-01-01

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis. PMID:24194931

Combined Effects of Feedforward Inhibition and Excitation in Thalamocortical Circuit on the Transitions of Epileptic Seizures

PubMed Central

Fan, Denggui; Duan, Lixia; Wang, Qian; Luan, Guoming

2017-01-01

The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC) to inhibitory neuronal population (IN) which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX). Inspired by this, we proposed a modified computational model by introducing feedforward inhibitory connectivity within thalamocortical circuit, to systematically investigate the combined effects of feedforward inhibition and excitation on transitions of epileptic seizures. We first found that the feedforward excitation can induce the transition from tonic oscillation to spike and wave discharges (SWD) in cortex, i.e., the epileptic tonic-absence seizures, with the fixed weak feedforward inhibition. Thereinto, the phase of absence seizures corresponding to strong feedforward excitation can be further transformed into the clonic oscillations with the increasing of feedforward inhibition, representing the epileptic absence-clonic seizures. We also observed the other fascinating dynamical states, such as periodic 2/3/4-spike and wave discharges, reversed SWD and clonic oscillations, as well as saturated firings. More importantly, we can identify the stable parameter regions representing the tonic-clonic oscillations and SWD discharges of epileptic seizures on the 2-D plane composed of feedforward inhibition and excitation, where the physiologically plausible transition pathways between tonic-clonic and absence seizures can be figured out. These results indicate the functional role of feedforward pathways in controlling epileptic seizures and the modified thalamocortical model may provide a guide for future efforts to mechanistically link feedforward pathways in the pathogenesis of epileptic seizures. PMID:28736520

Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

NASA Astrophysics Data System (ADS)

Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-05-01

Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

Acetylcholine-induced seizure-like activity and modified cholinergic gene expression in chronically epileptic rats.

PubMed

Zimmerman, Gabriel; Njunting, Marleisje; Ivens, Sebastian; Tolner, Else A; Tolner, Elsa; Behrens, Christoph J; Gross, Miriam; Soreq, Hermona; Heinemann, Uwe; Friedman, Alon

2008-02-01

The entorhinal cortex (EC) plays an important role in temporal lobe epilepsy. Under normal conditions, the enriched cholinergic innervation of the EC modulates local synchronized oscillatory activity; however, its role in epilepsy is unknown. Enhanced neuronal activation has been shown to induce transcriptional changes of key cholinergic genes and thus alter cholinergic responses. To examine cholinergic modulations in epileptic tissue we studied molecular and electrophysiological cholinergic responses in the EC of chronically epileptic rats following exposure to pilocarpine or kainic acid. We confirmed that while the total activity of the acetylcholine (ACh)-hydrolysing enzyme, acetylcholinesterase (AChE) was not altered, epileptic rats showed alternative splicing of AChE pre-mRNA transcripts, accompanied by a shift from membrane-bound AChE tetramers to soluble monomers. This was associated with increased sensitivity to ACh application: thus, in control rats, ACh (10-100 microm) induced slow (< 1Hz), periodic events confined to the EC; however, in epileptic rats, ACh evoked seconds-long seizure-like events with initial appearance in the EC, and frequent propagation to neighbouring cortical regions. ACh-induced seizure-like events could be completely blocked by the non-specific muscarinic antagonist, atropine, and were partially blocked by the muscarinic-1 receptor antagonist, pirenzepine; but were not affected by the non-specific nicotinic antagonist, mecamylamine. Epileptic rats presented reduced transcript levels of muscarinic receptors with no evidence of mRNA editing or altered mRNA levels for nicotinic ACh receptors. Our findings suggest that altered cholinergic modulation may initiate seizure events in the epileptic temporal cortex.

Genomics-Guided Precise Anti-Epileptic Drug Development.

PubMed

Delanty, Norman; Cavallleri, Gianpiero

2017-07-01

Traditional antiepileptic drug development approaches have yielded many important clinically valuable anti-epileptic drugs. However, the screening of promising compounds has been naturally agnostic to epilepsy etiology in individual human patients. Now, genomic medicine is changing the way we view human disease. International collaborations are unraveling the many molecular genetic causes of the epilepsies, including the early onset epileptic encephalopathies, and some of the familial focal epilepsies. Further advances in precision diagnostics will be facilitated by ongoing large collaborations and the wider availability of whole exome and whole genome sequencing in clinical practice. Securing a precise molecular diagnosis in some individual patients will pave the way for the advent of precision therapeutics of new and re-purposed compounds in the treatment of the epilepsies. This new approach is already beginning, e.g., with the use of everolimus in patients with tuberous sclerosis complex (and perhaps other mTORopathies), the use of quinidine in some children with KCNT1 mutations, and the use of the ketogenic diet in individuals with GLUT-1 deficiency. This article explores the promise of genomics guided drug development as an approach to complement the more traditional model.

Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats

PubMed Central

Tang, Nou-Ying; Ho, Tin-Yun; Chen, Chao-Hsiang

2017-01-01

Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p.) and subsequently investigated the effect of Uncaria rhynchophylla (UR) and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg). Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons. PMID:28386293

Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats.

PubMed

Tang, Nou-Ying; Lin, Yi-Wen; Ho, Tin-Yun; Cheng, Chin-Yi; Chen, Chao-Hsiang; Hsieh, Ching-Liang

2017-01-01

Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p.) and subsequently investigated the effect of Uncaria rhynchophylla (UR) and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg). Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons.

Quantitative complexity analysis in multi-channel intracranial EEG recordings form epilepsy brains

PubMed Central

Liu, Chang-Chia; Pardalos, Panos M.; Chaovalitwongse, W. Art; Shiau, Deng-Shan; Ghacibeh, Georges; Suharitdamrong, Wichai; Sackellares, J. Chris

2008-01-01

Epilepsy is a brain disorder characterized clinically by temporary but recurrent disturbances of brain function that may or may not be associated with destruction or loss of consciousness and abnormal behavior. Human brain is composed of more than 10 to the power 10 neurons, each of which receives electrical impulses known as action potentials from others neurons via synapses and sends electrical impulses via a sing output line to a similar (the axon) number of neurons. When neuronal networks are active, they produced a change in voltage potential, which can be captured by an electroencephalogram (EEG). The EEG recordings represent the time series that match up to neurological activity as a function of time. By analyzing the EEG recordings, we sought to evaluate the degree of underlining dynamical complexity prior to progression of seizure onset. Through the utilization of the dynamical measurements, it is possible to classify the state of the brain according to the underlying dynamical properties of EEG recordings. The results from two patients with temporal lobe epilepsy (TLE), the degree of complexity start converging to lower value prior to the epileptic seizures was observed from epileptic regions as well as non-epileptic regions. The dynamical measurements appear to reflect the changes of EEG’s dynamical structure. We suggest that the nonlinear dynamical analysis can provide a useful information for detecting relative changes in brain dynamics, which cannot be detected by conventional linear analysis. PMID:19079790

Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

PubMed Central

Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

2010-01-01

We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

Orthomolecular enhancement of human development

NASA Technical Reports Server (NTRS)

Pauling, L.

1978-01-01

The importance of molecules introduced into the human body by the way of foods is emphasized. Examples of orthomolecular therapy are given that range from the control of epileptic seizures, the therapy of mental illness, to the prevention of the common cold.

Perampanel, an antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, for the treatment of epilepsy: studies in human epileptic brain and nonepileptic brain and in rodent models.

PubMed

Zwart, R; Sher, E; Ping, X; Jin, X; Sims, J R; Chappell, A S; Gleason, S D; Hahn, P J; Gardinier, K; Gernert, D L; Hobbs, J; Smith, J L; Valli, S N; Witkin, J M

2014-10-01

Perampanel [Fycompa, 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile hydrate 4:3; Eisai Inc., Woodcliff Lake, NJ] is an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist used as an adjunctive treatment of partial-onset seizures. We asked whether perampanel has AMPA receptor antagonist activity in both the cerebral cortex and hippocampus associated with antiepileptic efficacy and also in the cerebellum associated with motor side effects in rodent and human brains. We also asked whether epileptic or nonepileptic human cortex is similarly responsive to AMPA receptor antagonism by perampanel. In rodent models, perampanel decreased epileptic-like activity in multiple seizure models. However, doses of perampanel that had anticonvulsant effects were within the same range as those engendering motor side effects. Perampanel inhibited native rat and human AMPA receptors from the hippocampus as well as the cerebellum that were reconstituted into Xenopus oocytes. In addition, with the same technique, we found that perampanel inhibited AMPA receptors from hippocampal tissue that had been removed from a patient who underwent surgical resection for refractory epilepsy. Perampanel inhibited AMPA receptor-mediated ion currents from all the tissues investigated with similar potency (IC50 values ranging from 2.6 to 7.0 μM). Cortical slices from the left temporal lobe derived from the same patient were studied in a 60-microelectrode array. Large field potentials were evoked on at least 45 channels of the array, and 10 μM perampanel decreased their amplitude and firing rate. Perampanel also produced a 33% reduction in the branching parameter, demonstrating the effects of perampanel at the network level. These data suggest that perampanel blocks AMPA receptors globally across the brain to account for both its antiepileptic and side-effect profile in rodents and epileptic patients. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Epidemiology of human toxocariasis in northern Italy.

PubMed

Genchi, C; Di Sacco, B; Gatti, S; Sangalli, G; Scaglia, M

1990-12-01

Sera from both clinically healthy adults (2112) and adult patients (471) were tested to assess the main risk factors for Toxocara infection in humans in Northern Italy. The patient group included 257 adult epileptics, 76 Strongyloides stercoralis-infected adult patients and 142 institutionalized mentally retarded adult patients. The overall seroprevalence in healthy population was 3.98%. No significant differences in seroprevalence were observed for sex, residence (urban or rural) or dog ownership, while seroprevalence significantly increased with age (18- greater than 51 years). Highest seroprevalence values were found in outdoor or soil-related workers. The seroprevalence was 4.35% in adult epileptics, 9.21% in Strongyloides stercoralis-infected patients and 14.47%-10.61% among institutionalized mentally retarded patients. These findings suggest that the prevalent source of human toxocariasis is the environmental contamination by infectious eggs of the parasite.

Increased neuronal beta-amyloid precursor protein expression in human temporal lobe epilepsy: association with interleukin-1 alpha immunoreactivity.

PubMed

Sheng, J G; Boop, F A; Mrak, R E; Griffin, W S

1994-11-01

Levels of immunoreactive beta-amyloid precursor protein and interleukin-1 alpha were found to be elevated in surgically resected human temporal lobe tissue from patients with intractable epilepsy compared with postmortem tissue from neurologically unaffected patients (controls). In tissue from epileptics, the levels of the 135-kDa beta-amyloid precursor protein isoform were elevated to fourfold (p < 0.05) those of controls and those of the 130-kDa isoform to threefold (p < 0.05), whereas those of the 120-kDa isoform (p > 0.05) were not different from control values. beta-Amyloid precursor protein-immunoreactive neurons were 16 times more numerous, and their cytoplasm and proximal processes were more intensely immunoreactive in tissue sections from epileptics than controls (133 +/- 12 vs. 8 +/- 3/mm2; p < 0.001). However, neither beta-amyloid precursor protein-immunoreactive dystrophic neurites nor beta-amyloid deposits were found in this tissue. Interleukin-1 alpha-immunoreactive cells (microglia) were three times more numerous in epileptics than in controls (80 +/- 8 vs. 25 +/- 5/mm2; p < 0.001), and these cells were often found adjacent to beta-amyloid precursor protein-immunoreactive neuronal cell bodies. Our findings, together with functions established in vitro for interleukin-1, suggest that increased expression of this protein contributes to the increased levels of beta-amyloid precursor protein in epileptics, thus indicating a potential role for both of these proteins in the neuronal dysfunctions, e.g., hyperexcitability, characteristic of epilepsy.

Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy.

PubMed

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.

EEG-confirmed epileptic activity in a cat with VGKC-complex/LGI1 antibody-associated limbic encephalitis.

PubMed

Pakozdy, Akos; Glantschnigg, Ursula; Leschnik, Michael; Hechinger, Harald; Moloney, Teresa; Lang, Bethan; Halasz, Peter; Vincent, Angela

2014-03-01

A 5-year-old, female client-owned cat presented with acute onset of focal epileptic seizures with orofacial twitching and behavioural changes. Magnetic resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was consistent with ictal epileptic seizure activity. After antiepileptic and additional corticosteroid treatment, the cat recovered and by 10 months of follow-up was seizure-free without any problem. Retrospectively, antibodies to LGI1, a component of the voltage-gated potassium channel-complex, were identified. Feline focal seizures with orofacial involvement have been increasingly recognised in client-owned cats, and autoimmune limbic encephalitis was recently suggested as a possible aetiology. This is the first report of EEG, MRI and long-term follow-up of this condition in cats which is similar to human limbic encephalitis.

A review of epidemiological data on epilepsy, phenobarbital, and risk of liver cancer.

PubMed

La Vecchia, Carlo; Negri, Eva

2014-01-01

Phenobarbital is not genotoxic, but has been related to promotion of liver cancer (as well as inhibition) in rodents. In October 2012, we carried out a systematic literature search in the Medline database and searched reference lists of retrieved publications. We identified 15 relevant papers. Epidemiological data on epileptics/anticonvulsant use and liver cancer were retrieved from eight reports from seven cohort (record linkage) studies of epileptics, and data on phenobarbital use from a pharmacy-based record linkage investigation of patients treated with phenobarbital (three reports), plus a case-control study nested in one of the cohort studies and including information on phenobarbital use. Of the studies of cancer in epileptics, two showed no excess risk of liver cancer. A long-term (1933-1984) Danish cohort study of epileptics found relative risks (RRs) of 4.7 [95% confidence interval (CI) 3.2-6.8] of liver cancer and of 2.2 (95% CI 1.2-3.5) of biliary tract cancers. Such apparent excess risks could, however, be largely or completely attributed to thorotrast, a contrast medium used in the past in epileptic patients for cerebral angiography. A Finnish cohort study of epileptics obtained an RR of 1.7 (95% CI 1.2-2.4). Such an apparent excess risk, however, was not related to phenobarbital or to any specific anticonvulsant drug. The long-term follow-up of two UK cohorts found some excess risk of liver cancer among severe, but not among mild, epileptics. Some excess risk of liver cancer was also found in cohort studies of patients hospitalized for epilepsy in Sweden and Taiwan, in the absence, however, of association with any specific drugs. A UK General Practice database, comparing epileptics treated with valproate with unexposed ones, found a very low incidence of liver cancer. Of the studies of cancer in patients treated with phenobarbital, a large US pharmacy-based cohort investigation showed no excess risk of liver cancer. In a case-control study, nested in the Danish cohort of epileptics, no association was observed between phenobarbital and liver cancer among patients who had not received thorotrast (RR=1.0 for liver and 0.8 for biliary tract cancers). Thus, some, although not all, studies reported excess risk of all cancers and liver cancer in severe, but not in milder epileptics. There is no evidence of a specific role of phenobarbital in human liver cancer risk, but data on the topic are limited.

Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling.

PubMed

Soriano, Jaymar; Kubo, Takatomi; Inoue, Takao; Kida, Hiroyuki; Yamakawa, Toshitaka; Suzuki, Michiyasu; Ikeda, Kazushi

2017-10-01

Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain's normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored.

Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling

PubMed Central

Inoue, Takao; Kida, Hiroyuki; Yamakawa, Toshitaka; Suzuki, Michiyasu

2017-01-01

Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain’s normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored. PMID:28981509

Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.

PubMed

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.

Investigating Neuromagnetic Brain Responses against Chromatic Flickering Stimuli by Wavelet Entropies

PubMed Central

Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

2009-01-01

Background Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Methodology/Principal Findings Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Conclusions/Significance Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations. PMID:19779630

Investigating neuromagnetic brain responses against chromatic flickering stimuli by wavelet entropies.

PubMed

Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

2009-09-25

Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations.

Measurement of Local Partial Pressure of Oxygen in the Brain Tissue under Normoxia and Epilepsy with Phosphorescence Lifetime Microscopy.

PubMed

Zhang, Cong; Bélanger, Samuel; Pouliot, Philippe; Lesage, Frédéric

2015-01-01

In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure.

A signal processing based analysis and prediction of seizure onset in patients with epilepsy

PubMed Central

Namazi, Hamidreza; Kulish, Vladimir V.

2016-01-01

One of the main areas of behavioural neuroscience is forecasting the human behaviour. Epilepsy is a central nervous system disorder in which nerve cell activity in the brain becomes disrupted, causing seizures or periods of unusual behaviour, sensations and sometimes loss of consciousness. An estimated 5% of the world population has epileptic seizure but there is not any method to cure it. More than 30% of people with epilepsy cannot control seizure. Epileptic seizure prediction, refers to forecasting the occurrence of epileptic seizures, is one of the most important but challenging problems in biomedical sciences, across the world. In this research we propose a new methodology which is based on studying the EEG signals using two measures, the Hurst exponent and fractal dimension. In order to validate the proposed method, it is applied to epileptic EEG signals of patients by computing the Hurst exponent and fractal dimension, and then the results are validated versus the reference data. The results of these analyses show that we are able to forecast the onset of a seizure on average of 25.76 seconds before the time of occurrence. PMID:26586477

Methionine increases BDNF DNA methylation and improves memory in epilepsy.

PubMed

Parrish, R Ryley; Buckingham, Susan C; Mascia, Katherine L; Johnson, Jarvis J; Matyjasik, Michal M; Lockhart, Roxanne M; Lubin, Farah D

2015-04-01

Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus. Using the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model. We found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade. Our findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

Classification of epileptic seizures using wavelet packet log energy and norm entropies with recurrent Elman neural network classifier.

PubMed

Raghu, S; Sriraam, N; Kumar, G Pradeep

2017-02-01

Electroencephalogram shortly termed as EEG is considered as the fundamental segment for the assessment of the neural activities in the brain. In cognitive neuroscience domain, EEG-based assessment method is found to be superior due to its non-invasive ability to detect deep brain structure while exhibiting superior spatial resolutions. Especially for studying the neurodynamic behavior of epileptic seizures, EEG recordings reflect the neuronal activity of the brain and thus provide required clinical diagnostic information for the neurologist. This specific proposed study makes use of wavelet packet based log and norm entropies with a recurrent Elman neural network (REN) for the automated detection of epileptic seizures. Three conditions, normal, pre-ictal and epileptic EEG recordings were considered for the proposed study. An adaptive Weiner filter was initially applied to remove the power line noise of 50 Hz from raw EEG recordings. Raw EEGs were segmented into 1 s patterns to ensure stationarity of the signal. Then wavelet packet using Haar wavelet with a five level decomposition was introduced and two entropies, log and norm were estimated and were applied to REN classifier to perform binary classification. The non-linear Wilcoxon statistical test was applied to observe the variation in the features under these conditions. The effect of log energy entropy (without wavelets) was also studied. It was found from the simulation results that the wavelet packet log entropy with REN classifier yielded a classification accuracy of 99.70 % for normal-pre-ictal, 99.70 % for normal-epileptic and 99.85 % for pre-ictal-epileptic.

High-performance liquid chromatography-tandem mass spectrometry method for the determination of perampanel, a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist in human plasma.

PubMed

Mano, Yuji; Takenaka, Osamu; Kusano, Kazutomi

2015-03-25

Perampanel (Fycompa(®)) is a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist registered for the adjunctive treatment of patients (≥12 years) with refractory partial onset seizures. In order to support clinical trials, as well as therapeutic drug monitoring, a sensitive bioanalytical method for the determination of perampanel concentrations in human plasma was established and validated using liquid chromatography with tandem mass spectrometry. Perampanel and an internal standard were extracted from human plasma (100 μL) by liquid extraction using methyl t-butyl ether, then evaporated and reconstituted. The chromatographic separation was conducted on a C8 column with isocratic elution at a flow rate of 0.2 mL/min. The established method showed linearity in the range 0.25-200 ng/mL with correlation coefficients of >0.99 that could be extended 10-fold as validated by dilution integrity analyses. No significant endogenous peaks were detected in the elution of analytes in blank human plasma and no significant matrix effect was observed. The intra- and inter-batch reproducibility analyses demonstrated accuracy and precision within the acceptance criteria. To check the impact of anti-epileptic drugs on the perampanel assay, accuracy, precision, and specificity were assessed in the presence of 14 anti-epileptic drugs. No anti-epileptic drugs at clinically relevant levels showed a significant impact on the perampanel assay. Copyright © 2014 Elsevier B.V. All rights reserved.

Altered metabolomic-genomic signature: A potential noninvasive biomarker of epilepsy.

PubMed

Wu, Helen C; Dachet, Fabien; Ghoddoussi, Farhad; Bagla, Shruti; Fuerst, Darren; Stanley, Jeffrey A; Galloway, Matthew P; Loeb, Jeffrey A

2017-09-01

This study aimed to identify noninvasive biomarkers of human epilepsy that can reliably detect and localize epileptic brain regions. Having noninvasive biomarkers would greatly enhance patient diagnosis, patient monitoring, and novel therapy development. At the present time, only surgically invasive, direct brain recordings are capable of detecting these regions with precision, which severely limits the pace and scope of both clinical management and research progress in epilepsy. We compared high versus low or nonspiking regions in nine medically intractable epilepsy surgery patients by performing integrated metabolomic-genomic-histological analyses of electrically mapped human cortical regions using high-resolution magic angle spinning proton magnetic resonance spectroscopy, cDNA microarrays, and histological analysis. We found a highly consistent and predictive metabolite logistic regression model with reduced lactate and increased creatine plus phosphocreatine and choline, suggestive of a chronically altered metabolic state in epileptic brain regions. Linking gene expression, cellular, and histological differences to these key metabolites using a hierarchical clustering approach predicted altered metabolic vascular coupling in the affected regions. Consistently, these predictions were validated histologically, showing both neovascularization and newly discovered, millimeter-sized microlesions. Using a systems biology approach on electrically mapped human cortex provides new evidence for spatially segregated, metabolic derangements in both neurovascular and synaptic architecture in human epileptic brain regions that could be a noninvasively detectable biomarker of epilepsy. These findings both highlight the immense power of a systems biology approach and identify a potentially important role that magnetic resonance spectroscopy can play in the research and clinical management of epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Measurement of Local Partial Pressure of Oxygen in the Brain Tissue under Normoxia and Epilepsy with Phosphorescence Lifetime Microscopy

PubMed Central

Zhang, Cong; Bélanger, Samuel; Pouliot, Philippe; Lesage, Frédéric

2015-01-01

In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure. PMID:26305777

[Clinical analysis of 322 cases of non-epileptic cerebral palsy].

PubMed

Zhu, Deng-Na; Wang, Jun; Jia, Yan-Jie; Niu, Guo-Hui; Sun, Li; Xiong, Hua-Chun; Zhai, Hong-Yin; Chen, Hai; Li, Lin-Chen

2010-12-01

To study the clinical features of non-epileptic seizures associated with cerebral palsy (CP) in children. A total of 1 198 children with CP (age: 9 months to 6 years) were enrolled. The children with paroxysmal events were monitored by 24 hrs video-EEG (VEEG) to make sure the seizures were epileptic or non-epileptic. The symptoms, age, CP types and EEG features were observed in children with non-epileptic CP. Five hundred and seventy-eight children (48.24%) presented paroxysmal events. The seizures were epileptic in 231 children (19.28%) and non-epileptic in 322 cases (26.88%). In the 322 cases of non-epileptic CP, the paroxysmal events were of various kinds, including non-epileptic seizure tonic, seizure shake head, shrug shoulder or head hypsokinesis, cry or scream, panic attacks, sleep myoclonic and stereotyped movement. One hundred and fifty-eight (49.1%) out of the 322 children demonstrated nonspecific EEG abnormalities. One hundred and eleven children (34.5%) were misdiagnosed as epilepsy in primary hospitals. The CP children less than one year old showed higher frequency of non-epileptic seizures than the age groups over 1 year and 3 to 6 years. The frequency of non-epileptic seizures was the highest in children with spastic CP (168 cases, 52.2%), followed by dyskinetic CP (69 cases, 21.4%) and mixed type CP (65 cases, 20.2%). The paroxysmal events in children with CP partially are non-epileptic seizures and it is important to differentiate non-epileptic from epileptic seizures. The frequencies of non-epileptic seizures may be associated with a child's age and CP type.

A new epileptic seizure classification based exclusively on ictal semiology.

PubMed

Lüders, H; Acharya, J; Baumgartner, C; Benbadis, S; Bleasel, A; Burgess, R; Dinner, D S; Ebner, A; Foldvary, N; Geller, E; Hamer, H; Holthausen, H; Kotagal, P; Morris, H; Meencke, H J; Noachtar, S; Rosenow, F; Sakamoto, A; Steinhoff, B J; Tuxhorn, I; Wyllie, E

1999-03-01

Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic syndromes, particularly focal epileptic syndromes. Modern advances in diagnostic technology, particularly in neuroimaging and molecular biology, now permit better definitions of epileptic syndromes. At the same time detailed studies showed that there does not necessarily exist a one-to-one relationship between epileptic seizures or electroclinical complexes and epileptic syndromes. These developments call for the reintroduction of an epileptic seizure classification based exclusively on clinical semiology, similar to the seizure classifications which were used by neurologists before the introduction of the modern diagnostic methods. This classification of epileptic seizures should always be complemented by an epileptic syndrome classification based on all the available clinical information (clinical history, neurological exam, ictal semiology, EEG, anatomical and functional neuroimaging, etc.). Such an approach is more consistent with mainstream clinical neurology and would avoid the current confusion between the classification of epileptic seizures (which in the International Seizure Classification is actually a classification of electroclinical complexes) and the classification of epileptic syndromes.

Sleeping in fits and starts: a practical guide to distinguishing nocturnal epilepsy from sleep disorders.

PubMed

Derry, Christopher P

2014-12-01

Accurately diagnosing sleep-related events, and particularly distinguishing nocturnal frontal lobe seizures from other sleep disorders such as parasomnias, can be challenging. This article reviews the differential diagnosis of paroxysmal events from sleep, epileptic and non-epileptic, considers important diagnostic points in the history, and evaluates the role of investigations in this setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Electroencephalography and epileptology in the 20th century].

PubMed

Karbowski, K

1995-12-05

In 1875, Caton was already able to detect cerebral electric currents during experimental studies in animals. In 1914, Cybulski and Jeleńska-Macieszyna reported on the increase of current-intensity during a focal motor epileptic seizure. In 1929 in Jena, Berger revolutionized the study of epilepsy with his paper on the human electroencephalogram 'Uber das Elektrenkephalogramm des Menschen'. His discovery and further publications as well as later works of numerous researchers, especially F. and E. Gibbs, Lennox, Penfield and Jasper, made it possible to distinguish different forms of 'little' epileptic seizures and to separate them from nonepileptic paroxysmal disorders. New epileptic syndromes could be singled out, as e.g. the symptomatic epilepsy of childhood with variable clinical manifestations of seizures and slow spike-wave complexes in the EEG (Lennox-Gastaut syndrome) or the benign partial epilepsy of childhood with centrotemporal EEG spikes. In these fields, as well as for the epileptic seizures in newborns and babies and for the differentiation between epileptic and nonepileptic twilight states in later stages of life, the EEG remains an indispensable tool in the CT and MRI era. It also contributes largely to the diagnosis of nonepileptic cerebral illness such as herpes simplex encephalitis, subacute sclerosing panencephalitis van Bogaert and Creutzfeldt-Jakob disease. Since the introduction of phenobarbital by Hauptmann in 1912, the palet of effective drugs against epilepsy, such as phenytoin, carbamazepine, valproate and benzodiazepines used for status-epilepticus treatment, became essentially larger. The value of newer substances (vigabatrin, progabide, gabapentin, lamotrigin) can't be estimated actually.(ABSTRACT TRUNCATED AT 250 WORDS)

Model-guided control of hippocampal discharges by local direct current stimulation.

PubMed

Mina, Faten; Modolo, Julien; Recher, Fanny; Dieuset, Gabriel; Biraben, Arnaud; Benquet, Pascal; Wendling, Fabrice

2017-05-10

Neurostimulation is an emerging treatment for drug-resistant epilepsies when surgery is contraindicated. Recent clinical results demonstrate significant seizure frequency reduction in epileptic patients, however the mechanisms underlying this therapeutic effect are largely unknown. This study aimed at gaining insights into local direct current stimulation (LDCS) effects on hyperexcitable tissue, by i) analyzing the impact of electrical currents locally applied on epileptogenic brain regions, and ii) characterizing currents achieving an "anti-epileptic" effect (excitability reduction). First, a neural mass model of hippocampal circuits was extended to accurately reproduce the features of hippocampal paroxysmal discharges (HPD) observed in a mouse model of epilepsy. Second, model predictions regarding current intensity and stimulation polarity were confronted to in vivo mice recordings during LDCS (n = 8). The neural mass model was able to generate realistic hippocampal discharges. Simulation of LDCS in the model pointed at a significant decrease of simulated HPD (in duration and occurrence rate, not in amplitude) for cathodal stimulation, which was successfully verified experimentally in epileptic mice. Despite the simplicity of our stimulation protocol, these results contribute to a better understanding of clinical benefits observed in epileptic patients with implanted neurostimulators. Our results also provide further support for model-guided design of neuromodulation therapy.

Topological properties of flat electroencephalography's state space

NASA Astrophysics Data System (ADS)

Ken, Tan Lit; Ahmad, Tahir bin; Mohd, Mohd Sham bin; Ngien, Su Kong; Suwa, Tohru; Meng, Ong Sie

2016-02-01

Neuroinverse problem are often associated with complex neuronal activity. It involves locating problematic cell which is highly challenging. While epileptic foci localization is possible with the aid of EEG signals, it relies greatly on the ability to extract hidden information or pattern within EEG signals. Flat EEG being an enhancement of EEG is a way of viewing electroencephalograph on the real plane. In the perspective of dynamical systems, Flat EEG is equivalent to epileptic seizure hence, making it a great platform to study epileptic seizure. Throughout the years, various mathematical tools have been applied on Flat EEG to extract hidden information that is hardly noticeable by traditional visual inspection. While these tools have given worthy results, the journey towards understanding seizure process completely is yet to be succeeded. Since the underlying structure of Flat EEG is dynamic and is deemed to contain wealthy information regarding brainstorm, it would certainly be appealing to explore in depth its structures. To better understand the complex seizure process, this paper studies the event of epileptic seizure via Flat EEG in a more general framework by means of topology, particularly, on the state space where the event of Flat EEG lies.

Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with Disinhibition

NASA Astrophysics Data System (ADS)

Fan, Denggui; Liu, Suyu; Wang, Qingyun

2016-11-01

Epileptic absence seizure characterized by the typical 2-4 Hz spike-wave discharges (SWD) are known to arise due to the physiologically abnormal interactions within the thalamocortical network. By introducing a second inhibitory neuronal population in the cortical system, here we propose a modified thalamocortical field model to mathematically describe the occurrences and transitions of SWD under the mutual functions between cortex and thalamus, as well as the disinhibitory modulations of SWD mediated by the two different inhibitory interneuronal populations. We first show that stimulation can induce the recurrent seizures of SWD in the modified model. Also, we demonstrate the existence of various types of firing states including the SWD. Moreover, we can identify the bistable parametric regions where the SWD can be both induced and terminated by stimulation perturbations applied in the background resting state. Interestingly, in the absence of stimulation disinhibitory functions between the two different interneuronal populations can also both initiate and abate the SWD, which suggests that the mechanism of disinhibition is comparable to the effect of stimulation in initiating and terminating the epileptic SWD. Hopefully, the obtained results can provide theoretical evidences in exploring dynamical mechanism of epileptic seizures.

The GABAB receptor agonist, baclofen, contributes to three distinct varieties of amnesia in the human brain - A detailed case report.

PubMed

Zeman, Adam; Hoefeijzers, Serge; Milton, Fraser; Dewar, Michaela; Carr, Melanie; Streatfield, Claire

2016-01-01

We describe a patient in whom long-term, therapeutic infusion of the selective gamma-amino-butyric acid type B (GABAB) receptor agonist, baclofen, into the cerebrospinal fluid (CSF) gave rise to three distinct varieties of memory impairment: i) repeated, short periods of severe global amnesia, ii) accelerated long-term forgetting (ALF), evident over intervals of days and iii) a loss of established autobiographical memories. This pattern of impairment has been reported in patients with temporal lobe epilepsy (TLE), in particular the subtype of Transient Epileptic Amnesia (TEA). The amnesic episodes and accelerated forgetting remitted on withdrawal of baclofen, while the autobiographical amnesia (AbA) persisted. This exceptional case highlights the occurrence of 'non-standard' forms of human amnesia, reflecting the biological complexity of memory processes. It suggests a role for GABAB signalling in the modulation of human memory over multiple time-scales and hints at its involvement in 'epileptic amnesia'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of pseudosinusoidal epileptic seizure segments in the neonatal EEG by cascading a rule-based algorithm with a neural network.

PubMed

Karayiannis, Nicolaos B; Mukherjee, Amit; Glover, John R; Ktonas, Periklis Y; Frost, James D; Hrachovy, Richard A; Mizrahi, Eli M

2006-04-01

This paper presents an approach to detect epileptic seizure segments in the neonatal electroencephalogram (EEG) by characterizing the spectral features of the EEG waveform using a rule-based algorithm cascaded with a neural network. A rule-based algorithm screens out short segments of pseudosinusoidal EEG patterns as epileptic based on features in the power spectrum. The output of the rule-based algorithm is used to train and compare the performance of conventional feedforward neural networks and quantum neural networks. The results indicate that the trained neural networks, cascaded with the rule-based algorithm, improved the performance of the rule-based algorithm acting by itself. The evaluation of the proposed cascaded scheme for the detection of pseudosinusoidal seizure segments reveals its potential as a building block of the automated seizure detection system under development.

Lack of pathogenic mutations in SOS1 gene in phenytoin-induced gingival overgrowth patients.

PubMed

Margiotti, Katia; Pascolini, Giulia; Consoli, Federica; Guida, Valentina; Di Bonaventura, Carlo; Giallonardo, Anna Teresa; Pizzuti, Antonio; De Luca, Alessandro

2017-08-01

Gingival overgrowth is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers. One of the main drugs associated with gingival overgrowth is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. It has been shown that mutation of human SOS1 gene is responsible for a rare hereditary gingival fibromatosis type 1, a benign gingival overgrowth. The aim of the present study is to evaluate the possible contribution of SOS1 mutation to gingival overgrowth-related phenotype. We selected and screened for mutations a group of 24 epileptic patients who experienced significant gingival overgrowth following phenytoin therapy. Mutation scanning was carried out by denaturing high-performance liquid chromatography analysis of the entire coding region of the SOS1 gene. Novel identified variants were analyzed in-silico by using Alamut Visual mutation interpretation software, and comparison with normal control group was done. Mutation scanning of the entire coding sequence of SOS1 gene identified seven intronic variants and one new exonic substitution (c.138G>A). The seven common intronic variants were not considered to be of pathogenic importance. The exonic substitution c.138G>A was found to be absent in 100 ethnically matched normal control chromosomes, but was not expected to have functional significance based on prediction bioinformatics tools. This study represents the first mutation analysis of the SOS1 gene in phenytoin-induced gingival overgrowth epileptic patients. Present results suggest that obvious pathogenic mutations in the SOS1 gene do not represent a common mechanism underlying phenytoin-induced gingival overgrowth in epileptic patients; other mechanisms are likely to be involved in the pathogenesis of this drug-induced phenotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multimodal effective connectivity analysis reveals seizure focus and propagation in musicogenic epilepsy.

PubMed

Klamer, Silke; Rona, Sabine; Elshahabi, Adham; Lerche, Holger; Braun, Christoph; Honegger, Jürgen; Erb, Michael; Focke, Niels K

2015-06-01

Dynamic causal modeling (DCM) is a method to non-invasively assess effective connectivity between brain regions. 'Musicogenic epilepsy' is a rare reflex epilepsy syndrome in which seizures can be elicited by musical stimuli and thus represents a unique possibility to investigate complex human brain networks and test connectivity analysis tools. We investigated effective connectivity in a case of musicogenic epilepsy using DCM for fMRI, high-density (hd-) EEG and MEG and validated results with intracranial EEG recordings. A patient with musicogenic seizures was examined using hd-EEG/fMRI and simultaneous '256-channel hd-EEG'/'whole head MEG' to characterize the epileptogenic focus and propagation effects using source analysis techniques and DCM. Results were validated with invasive EEG recordings. We recorded one seizure with hd-EEG/fMRI and four auras with hd-EEG/MEG. During the seizures, increases of activity could be observed in the right mesial temporal region as well as bilateral mesial frontal regions. Effective connectivity analysis of fMRI and hd-EEG/MEG indicated that right mesial temporal neuronal activity drives changes in the frontal areas consistently in all three modalities, which was confirmed by the results of invasive EEG recordings. Seizures thus seem to originate in the right mesial temporal lobe and propagate to mesial frontal regions. Using DCM for fMRI, hd-EEG and MEG we were able to correctly localize focus and propagation of epileptic activity and thereby characterize the underlying epileptic network in a patient with musicogenic epilepsy. The concordance between all three functional modalities validated by invasive monitoring is noteworthy, both for epileptic activity spread as well as for effective connectivity analysis in general. Copyright © 2015 Elsevier Inc. All rights reserved.

Mapping Epileptic Activity: Sources or Networks for the Clinicians?

PubMed Central

Pittau, Francesca; Mégevand, Pierre; Sheybani, Laurent; Abela, Eugenio; Grouiller, Frédéric; Spinelli, Laurent; Michel, Christoph M.; Seeck, Margitta; Vulliemoz, Serge

2014-01-01

Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity. PMID:25414692

Patterns of human local cerebral glucose metabolism during epileptic seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

1982-10-01

Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

Human sexual behavior related to pathology and activity of the brain.

PubMed

Komisaruk, Barry R; Rodriguez Del Cerro, Maria Cruz

2015-01-01

Reviewed in this chapter are: (1) correlations among human sexual behavior, brain pathology, and brain activity, including caveats regarding the interpretation of "cause and effect" among these factors, and the degree to which "hypersexuality" and reported changes in sexual orientation correlated with brain pathology are uniquely sexual or are attributable to a generalized disinhibition of brain function; (2) the effects, in some cases inhibitory, in others facilitatory, on sexual behavior and motivation, of stroke, epileptic seizures, traumatic brain injury, and brain surgery; and (3) insights into sexual motivation and behavior recently gained from functional brain imaging research and its interpretive limitations. We conclude from the reviewed research that the neural orchestra underlying the symphony of human sexuality comprises, rather than brain "centers," multiple integrated brain systems, and that there are more questions than answers in our understanding of the control of human sexual behavior by the brain - a level of understanding that is still in embryonic form. © 2015 Elsevier B.V. All rights reserved.

Spatiotemporal source analysis in scalp EEG vs. intracerebral EEG and SPECT: a case study in a 2-year-old child.

PubMed

Aarabi, A; Grebe, R; Berquin, P; Bourel Ponchel, E; Jalin, C; Fohlen, M; Bulteau, C; Delalande, O; Gondry, C; Héberlé, C; Moullart, V; Wallois, F

2012-06-01

This case study aims to demonstrate that spatiotemporal spike discrimination and source analysis are effective to monitor the development of sources of epileptic activity in time and space. Therefore, they can provide clinically useful information allowing a better understanding of the pathophysiology of individual seizures with time- and space-resolved characteristics of successive epileptic states, including interictal, preictal, postictal, and ictal states. High spatial resolution scalp EEGs (HR-EEG) were acquired from a 2-year-old girl with refractory central epilepsy and single-focus seizures as confirmed by intracerebral EEG recordings and ictal single-photon emission computed tomography (SPECT). Evaluation of HR-EEG consists of the following three global steps: (1) creation of the initial head model, (2) automatic spike and seizure detection, and finally (3) source localization. During the source localization phase, epileptic states are determined to allow state-based spike detection and localization of underlying sources for each spike. In a final cluster analysis, localization results are integrated to determine the possible sources of epileptic activity. The results were compared with the cerebral locations identified by intracerebral EEG recordings and SPECT. The results obtained with this approach were concordant with those of MRI, SPECT and distribution of intracerebral potentials. Dipole cluster centres found for spikes in interictal, preictal, ictal and postictal states were situated an average of 6.3mm from the intracerebral contacts with the highest voltage. Both amplitude and shape of spikes change between states. Dispersion of the dipoles was higher in the preictal state than in the postictal state. Two clusters of spikes were identified. The centres of these clusters changed position periodically during the various epileptic states. High-resolution surface EEG evaluated by an advanced algorithmic approach can be used to investigate the spatiotemporal characteristics of sources located in the epileptic focus. The results were validated by standard methods, ensuring good spatial resolution by MRI and SPECT and optimal temporal resolution by intracerebral EEG. Surface EEG can be used to identify different spike clusters and sources of the successive epileptic states. The method that was used in this study will provide physicians with a better understanding of the pathophysiological characteristics of epileptic activities. In particular, this method may be useful for more effective positioning of implantable intracerebral electrodes. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Genetics Home Reference: early infantile epileptic encephalopathy 1

MedlinePlus

... infantile epileptic encephalopathy 1 Early infantile epileptic encephalopathy 1 Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Early infantile epileptic encephalopathy 1 (EIEE1) is ...

Cyclooxygenase system contributes to the maintenance of post convulsive period of epileptic phenomena in the genetically epileptic El mice.

PubMed

Okada, Kazumasa; Yamashita, Uki; Tsuji, Sadatoshi

2006-09-01

Recent studies have shown that cytokines and cyclooxygenase (COX)-2 are up-regulated in the brain of human epilepsy patients and animal models of epilepsy. We investigated the effect of inflammatory responses induced by intramuscular injection of turpentine on the epileptic phenomenon in genetically epileptic El mice. As parameters of epileptic seizure, seizure threshold (number of toss-ups to induce convulsion), duration of actual convulsion and duration of post actual convulsive period (period from the offset of convulsion to full recovery) were evaluated. The post actual convulsive period was prolonged without any change of seizure threshold or duration of actual convulsion 24 h after turpentine injection. Although pretreatment with indomethacin for one week did not change the seizure parameters, indomethacin suppressed the prolongation of the post actual convulsive period induced by turpentine. The mRNA expression of IL-1beta, IL-6 and COX-2 in the cerebral cortex was detected by RT-PCR. There was no difference in the mRNA expression in the cerebral cortex before and 24 h after seizure. The mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex were up-regulated 24 h after turpentine injection. On the other hand, the up-regulated mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex after turpentine treatment were not suppressed by indomethacin. These results suggest that prostaglandins induced with COX-2 in the cerebral cortex seem to play an important role in the maintenance of the post convulsive period, but not in induction and maintenance of the actual convulsive state.

Development of a multichannel optical system for differential cortical measurement

NASA Astrophysics Data System (ADS)

Maki, Atsushi; Yamashita, Yuichi; Watanabe, Eiju; Koizumi, Hideaki

1997-08-01

A prototype system based on intensity-modulation spectroscopy (IMS) was produced with the goal of developing 'optoencephalography' as a new instrument for clinical application and for investigating human brain functions. This system can use dual wavelengths (787 and 827 nm) to simultaneously measure reflectances at 8 measurement positions on the human head. Using the system, we measured the changes in blood circulation and oxygenation changes caused by epileptic seizures and specific brain functions. The former measurements were made simultaneously with tests to determine the epileptic focus by using single-photon-emission computed tomography (SPECT) and electrodes set in the brian. Four measurement positions were fixed in each temporal region. The areas where cerebral blood flow increased, as observed by SPECT, corresponded to the positions where the regional cerebral blood volume (rCBV) increased, as measured by the IMS system. Furthermore, the timing of the epileptic seizures, as measured by the depth-electrodes, corresponded to the timing of the increase in rCBV measured by the prototype system. Our measurements of changes in blood circulation as a result of brain functions were made for motor functions to compare the differences between the right and left hemisphere in how they respond to specific functions. Four measurement positions were set in bilateral motor areas. Significant differences in blood circulation in connection with brain activities were observed between the right and left hemispheres.

Stability of Synchronization Clusters and Seizurability in Temporal Lobe Epilepsy

PubMed Central

Palmigiano, Agostina; Pastor, Jesús; García de Sola, Rafael; Ortega, Guillermo J.

2012-01-01

Purpose Identification of critical areas in presurgical evaluations of patients with temporal lobe epilepsy is the most important step prior to resection. According to the “epileptic focus model”, localization of seizure onset zones is the main task to be accomplished. Nevertheless, a significant minority of epileptic patients continue to experience seizures after surgery (even when the focus is correctly located), an observation that is difficult to explain under this approach. However, if attention is shifted from a specific cortical location toward the network properties themselves, then the epileptic network model does allow us to explain unsuccessful surgical outcomes. Methods The intraoperative electrocorticography records of 20 patients with temporal lobe epilepsy were analyzed in search of interictal synchronization clusters. Synchronization was analyzed, and the stability of highly synchronized areas was quantified. Surrogate data were constructed and used to statistically validate the results. Our results show the existence of highly localized and stable synchronization areas in both the lateral and the mesial areas of the temporal lobe ipsilateral to the clinical seizures. Synchronization areas seem to play a central role in the capacity of the epileptic network to generate clinical seizures. Resection of stable synchronization areas is associated with elimination of seizures; nonresection of synchronization clusters is associated with the persistence of seizures after surgery. Discussion We suggest that synchronization clusters and their stability play a central role in the epileptic network, favoring seizure onset and propagation. We further speculate that the stability distribution of these synchronization areas would differentiate normal from pathologic cases. PMID:22844524

Computational models of epilepsy.

PubMed

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.

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants.

PubMed

Talat, Mohamed A; Ahmed, Anwar; Mohammed, Lamia

2015-10-01

To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1 ± 3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. The mean zinc level was 60.1 ± 22.6 ug/dl in the cases, and 102.1 ± 18 ug/dl in the controls (p<0.001). The mean copper level was 180.1 ± 32.4 ug/dl in cases compared with 114.5 ± 18.5 ug/dl in controls (p<0.001). Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients.

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

PubMed Central

Talat, Mohamed A.; Ahmed, Anwar; Mohammed, Lamia

2015-01-01

Objective: To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. Methods: A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. Results: The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001). Conclusion: Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients. PMID:26492112

Dynamic Granger-Geweke causality modeling with application to interictal spike propagation

PubMed Central

Lin, Fa-Hsuan; Hara, Keiko; Solo, Victor; Vangel, Mark; Belliveau, John W.; Stufflebeam, Steven M.; Hamalainen, Matti S.

2010-01-01

A persistent problem in developing plausible neurophysiological models of perception, cognition, and action is the difficulty of characterizing the interactions between different neural systems. Previous studies have approached this problem by estimating causal influences across brain areas activated during cognitive processing using Structural Equation Modeling and, more recently, with Granger-Geweke causality. While SEM is complicated by the need for a priori directional connectivity information, the temporal resolution of dynamic Granger-Geweke estimates is limited because the underlying autoregressive (AR) models assume stationarity over the period of analysis. We have developed a novel optimal method for obtaining data-driven directional causality estimates with high temporal resolution in both time and frequency domains. This is achieved by simultaneously optimizing the length of the analysis window and the chosen AR model order using the SURE criterion. Dynamic Granger-Geweke causality in time and frequency domains is subsequently calculated within a moving analysis window. We tested our algorithm by calculating the Granger-Geweke causality of epileptic spike propagation from the right frontal lobe to the left frontal lobe. The results quantitatively suggested the epileptic activity at the left frontal lobe was propagated from the right frontal lobe, in agreement with the clinical diagnosis. Our novel computational tool can be used to help elucidate complex directional interactions in the human brain. PMID:19378280

[Video electroencephalographic diagnosis of epileptic and non-epileptic paroxysmal episodes in infants and children at the pre-school age].

PubMed

Pérez-Jiménez, Angeles; García-Fernández, Marta; Santiago, M del Mar; Fournier-Del Castillo, M Concepción

2012-05-21

The main usefulness of video electroencephalographic (video-EEG) monitoring lies in the fact that it allows proper classification of the type of epileptic seizure and epileptic syndrome, identification of minor seizures, location of the epileptogenic zone and differentiation between epileptic seizures and non-epileptic paroxysmal manifestations (NEPM). In infants and pre-school age children, the clinical signs with which epileptic seizures are expressed differ to those of older children, seizures with bilateral motor signs such as epileptic spasms, tonic and myoclonic seizures predominate, and seizures with interruption of activity or hypomotor seizures, and no prominent automatisms are observed. In children with focal epilepsies, focal and generalised signs are often superposed, both clinically and in the EEG. NEPM may be benign transitory disorders or they can be episodic symptoms of different neurological or psychopathological disorders. NEPM are often observed in children with mental retardation, neurological compromise or autism spectrum disorders, who present epileptic seizures and epileptiform abnormalities in the baseline EEG. It then becomes necessary to determine which episodes correspond to epileptic seizures and which do not. The NEPM that are most frequently registered in the video-EEG in infants and pre-school age children are unexpected sudden motor contractions ('spasms'), introspective tendencies, motor stereotypic movements and paroxysmal sleep disorders.

Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus.

PubMed

Isokawa, M

1996-05-01

1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to give rise to epileptic excitation in chronically seizure-prone hippocampus.

Weather as a risk factor for epileptic seizures: A case-crossover study.

PubMed

Rakers, Florian; Walther, Mario; Schiffner, Rene; Rupprecht, Sven; Rasche, Marius; Kockler, Michael; Witte, Otto W; Schlattmann, Peter; Schwab, Matthias

2017-07-01

Most epileptic seizures occur unexpectedly and independently of known risk factors. We aimed to evaluate the clinical significance of patients' perception that weather is a risk factor for epileptic seizures. Using a hospital-based, bidirectional case-crossover study, 604 adult patients admitted to a large university hospital in Central Germany for an unprovoked epileptic seizure between 2003 and 2010 were recruited. The effect of atmospheric pressure, relative air humidity, and ambient temperature on the onset of epileptic seizures under temperate climate conditions was estimated. We found a close-to-linear negative correlation between atmospheric pressure and seizure risk. For every 10.7 hPa lower atmospheric pressure, seizure risk increased in the entire study population by 14% (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.01-1.28). In patients with less severe epilepsy treated with one antiepileptic medication, seizure risk increased by 36% (1.36, 1.09-1.67). A high relative air humidity of >80% increased seizure risk in the entire study population by up to 48% (OR 1.48, 95% CI 1.11-1.96) 3 days after exposure in a J-shaped association. High ambient temperatures of >20°C decreased seizure risk by 46% in the overall study population (OR 0.54, 95% CI 0.32-0.90) and in subgroups, with the greatest effects observed in male patients (OR 0.33, 95% CI 0.14-0.74). Low atmospheric pressure and high relative air humidity are associated with an increased risk for epileptic seizures, whereas high ambient temperatures seem to decrease seizure risk. Weather-dependent seizure risk may be accentuated in patients with less severe epilepsy. Our results require further replication across different climate regions and cohorts before reliable clinical recommendations can be made. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Fibromyalgia and seizures.

PubMed

Tatum, William O; Langston, Michael E; Acton, Emily K

2016-06-01

The purpose of this case-matched study was to determine how frequently fibromyalgia is associated with different paroxysmal neurological disorders and explore the utility of fibromyalgia as a predictor for the diagnosis of psychogenic non-epileptic seizures. The billing diagnosis codes of 1,730 new, non-selected patient encounters were reviewed over a three-year period for an epileptologist in a neurology clinic to identify all patients with historical diagnoses of fibromyalgia. The frequency with which epileptic seizures, psychogenic non-epileptic seizures, and physiological non-epileptic events were comorbid with fibromyalgia was assessed. Age and gender case-matched controls were used for a between-group comparison. Wilcoxon tests were used to analyse interval data, and Chi-square was used to analyse categorical data (p<0.05). Fibromyalgia was retrospectively identified in 95/1,730 (5.5%) patients in this cohort. Females represented 95% of the fibromyalgia sample (age: 53 years; 95% CI: 57, 51). Forty-three percent of those with fibromyalgia had a non-paroxysmal, neurological primary clinical diagnosis, most commonly chronic pain. Paroxysmal events were present in 57% of fibromyalgia patients and 54% of case-matched controls. Among patients with fibromyalgia and paroxysmal disorders, 11% had epileptic seizures, 74% had psychogenic non-epileptic seizures, and 15% had physiological non-epileptic events, compared to case-matched controls with 37% epileptic seizures, 51% psychogenic non-epileptic events, and 12% physiological non-epileptic events (p = 0.009). Fibromyalgia was shown to be a predictor for the diagnosis of psychogenic non-epileptic seizures in patients with undifferentiated paroxysmal spells. However, our results suggest that the specificity and sensitivity of fibromyalgia as a marker for psychogenic non-epileptic seizures in a mixed general neurological population of patients is less than previously described.

Magnetic resonance features of the feline hippocampus in epileptic and non-epileptic cats: a blinded, retrospective, multi-observer study.

PubMed

Claßen, Anne Christine; Kneissl, Sibylle; Lang, Johann; Tichy, Alexander; Pakozdy, Akos

2016-08-11

Hippocampal necrosis in cats has been reported to be associated with epileptic seizures. Magnetic resonance imaging (MRI) features of temporal lobe (TL) abnormalities in epileptic cats have been described but MR images from epileptic and non-epileptic individuals have not yet been systematically compared. TL abnormalities are highly variable in shape, size and signal, and therefore may lead to varying evaluations by different specialists. The aim of this study was to investigate whether there were differences in the appearance of the TL between epileptic and non-epileptic cats, and whether there were any relationships between TL abnormalities and seizure semiologies or other clinical findings. We also investigated interobserver agreement among three specialists. The MR images of 46 cats were reviewed independently by three observers, who were blinded to patient data, examination findings and the review of the other observers. Images were evaluated using a multiparametric scoring system developed for this study. Mann-Whitney U-tests and chi-square were used to analyse the differences between observers' evaluations. The kappa coefficient (k) and Fleiss' kappa coefficient were used to quantify interobserver agreement. The overall interobserver agreement was moderate to good (k =0.405 to 0.615). The MR scores between epileptic and non-epileptic cats did not differ significantly. However, there was a significant difference between the MR scores of epileptic cats with and without orofacial involvement according to all three observers. Likewise, MR scores of cats with cluster seizures were higher than those of cats without clusters. Cats presenting with recurrent epileptic seizures with orofacial involvement are more likely to have hippocampal pathologies, which suggests that TL abnormalities are not merely unspecific epileptic findings, but are associated with a certain type of epilepsy. TL signal alterations are more likely to be detected on FLAIR sequences. In contrast to severe changes in the TL which were described similarly among specialists, mild TL abnormalities may be difficult to interpret, thus leading to different assessments among observers.

Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials

PubMed Central

Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

2014-01-01

The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm2 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant’s left middle temporal gyrus. In this participant, spectral power in 0.3–10 Hz, 20–55 Hz, and 125–250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly and reliably detect human seizures. PMID:24663490

[Drawing of the family and of the human figure: a comparative study between children with epilepsy and a control group].

PubMed

Gomes-Correia, A

In this study our aim was to get to know children with epilepsy through their drawings. In this case the drawings of the human figure and the family were chosen. The population which was studied included 32 children: 16 of these children had epilepsy and the 16 others were the control group. From the comparison performed between these two groups of children it was found that in relation to family drawings children with epilepsy tend more to draw their own family than children in the control group. As for the drawing of the human figure and the global analysis of the body figure it was found that the mental age of the isolated character and the higher level character drawn by epileptic children was inferior to chronological age, while the reverse was true in the drawings of the control group. In relation to the analysis of structural cohesion in the representation of the body it was found that hands were absent in the drawings of epileptic children.

Nonlinear analyses of interictal EEG map the brain interdependences in human focal epilepsy

NASA Astrophysics Data System (ADS)

Quyen, Michel Le Van; Martinerie, Jacques; Adam, Claude; Varela, Francisco J.

1999-03-01

The degree of interdependence between intracranial electroencephalographic (EEG) channels was investigated in epileptic patients with temporal lobe seizures during interictal (between seizures) periods. With a novel method to characterize nonlinear cross-predictability, that is, the predictability of one channel using another channel as data base, we demonstrated here a possibility to extract information on the spatio-temporal organization of interactions between multichannel recording sites. This method determines whether two channels contain common activity, and often, whether one channel contains activity induced by the activity of the other channel. In particular, the technique and the comparison with surrogate data demonstrated that transient large-scale nonlinear entrainments by the epileptogenic region can be identified, this with or without epileptic activity. Furthermore, these recurrent activities related with the epileptic foci occurred in well-defined spatio-temporal patterns. This suggests that the epileptogenic region can exhibit very subtle influences on other brain regions during an interictal period and raises the possibility that the cross-predictability analysis of interictal data may be used as a significant aid in locating epileptogenic foci.

[Research advances in circadian rhythm of epileptic seizures].

PubMed

Yang, Wen-Qi; Li, Hong

2017-01-01

The time phase of epileptic seizures has attracted more and more attention. Epileptic seizures have their own circadian rhythm. The same type of epilepsy has different seizure frequencies in different time periods and states (such as sleeping/awakening state and natural day/night cycle). The circadian rhythm of epileptic seizures has complex molecular and endocrine mechanisms, and currently there are several hypotheses. Clarification of the circadian rhythm of epileptic seizures and prevention and administration according to such circadian rhythm can effectively control seizures and reduce the adverse effects of drugs. The research on the circadian rhythm of epileptic seizures provides a new idea for the treatment of epilepsy.

Brain Regions Underlying Word Finding Difficulties in Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Trebuchon-Da Fonseca, Agnes; Guedj, Eric; Alario, F-Xavier; Laguitton, Virginie; Mundler, Olivier; Chauvel, Patrick; Liegeois-Chauvel, Catherine

2009-01-01

Word finding difficulties are often reported by epileptic patients with seizures originating from the language dominant cerebral hemisphere, for example, in temporal lobe epilepsy. Evidence regarding the brain regions underlying this deficit comes from studies of peri-operative electro-cortical stimulation, as well as post-surgical performance.…

Differentiating epileptic from non-epileptic high frequency intracerebral EEG signals with measures of wavelet entropy.

PubMed

Mooij, Anne H; Frauscher, Birgit; Amiri, Mina; Otte, Willem M; Gotman, Jean

2016-12-01

To assess whether there is a difference in the background activity in the ripple band (80-200Hz) between epileptic and non-epileptic channels, and to assess whether this difference is sufficient for their reliable separation. We calculated mean and standard deviation of wavelet entropy in 303 non-epileptic and 334 epileptic channels from 50 patients with intracerebral depth electrodes and used these measures as predictors in a multivariable logistic regression model. We assessed sensitivity, positive predictive value (PPV) and negative predictive value (NPV) based on a probability threshold corresponding to 90% specificity. The probability of a channel being epileptic increased with higher mean (p=0.004) and particularly with higher standard deviation (p<0.0001). The performance of the model was however not sufficient for fully classifying the channels. With a threshold corresponding to 90% specificity, sensitivity was 37%, PPV was 80%, and NPV was 56%. A channel with a high standard deviation of entropy is likely to be epileptic; with a threshold corresponding to 90% specificity our model can reliably select a subset of epileptic channels. Most studies have concentrated on brief ripple events. We showed that background activity in the ripple band also has some ability to discriminate epileptic channels. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A subharmonic dynamical bifurcation during in vitro epileptiform activity

NASA Astrophysics Data System (ADS)

Perez Velazquez, Jose L.; Khosravani, Houman

2004-06-01

Epileptic seizures are considered to result from a sudden change in the synchronization of firing neurons in brain neural networks. We have used an in vitro model of status epilepticus (SE) to characterize dynamical regimes underlying the observed seizure-like activity. Time intervals between spikes or bursts were used as the variable to construct first-return interpeak or interburst interval plots, for studying neuronal population activity during the transition to seizure, as well as within seizures. Return maps constructed for a brief epoch before seizures were used for approximating the local system dynamics during that time window. Analysis of the first-return maps suggests that intermittency is a dynamical regime underlying the observed epileptic activity. This type of analysis may be useful for understanding the collective dynamics of neuronal populations in the normal and pathological brain.

Temporal-spatial characteristics of phase-amplitude coupling in electrocorticogram for human temporal lobe epilepsy.

PubMed

Zhang, Ruihua; Ren, Ye; Liu, Chunyan; Xu, Na; Li, Xiaoli; Cong, Fengyu; Ristaniemi, Tapani; Wang, YuPing

2017-09-01

Neural activity of the epileptic human brain contains low- and high-frequency oscillations in different frequency bands, some of which have been used as reliable biomarkers of the epileptogenic brain areas. However, the relationship between the low- and high-frequency oscillations in different cortical areas during the period from pre-seizure to post-seizure has not been completely clarified. We recorded electrocorticogram data from the temporal lobe and hippocampus of seven patients with temporal lobe epilepsy. The modulation index based on the Kullback-Leibler distance and the phase-amplitude coupling co-modulogram were adopted to quantify the coupling strength between the phase of low-frequency oscillations (0.2-10Hz) and the amplitude of high-frequency oscillations (11-400Hz) in different seizure epochs. The time-varying phase-amplitude modulogram was used to analyze the phase-amplitude coupling pattern during the entire period from pre-seizure to post-seizure in both the left and right temporal lobe and hippocampus. Channels with strong modulation index were compared with the seizure onset channels identified by the neurosurgeons and the resection channels in the clinical surgery. The phase-amplitude coupling strength (modulation index) increased significantly in the mid-seizure epoch and decrease significantly in seizure termination and post-seizure epochs (p<0.001). The strong phase-amplitude-modulating low- and high-frequency oscillations in the mid-seizure epoch were mainly δ, θ, and α oscillations and γ and ripple oscillations, respectively. The phase-amplitude modulation and strength varied among channels and was asymmetrical in the left and right temporal cortex and hippocampus. The "fall-max" phase-amplitude modulation pattern, i.e., high-frequency amplitudes were largest in the low-frequency phase range [-π, 0], which corresponded to the falling edges of low-frequency oscillations, appeared in the middle period of the seizures at epileptic focus channels. Channels with strong modulation index appeared on the corresponding left or right temporal cortex of surgical resection and overlapped with the clinical resection zones in all patients. The "fall-max" pattern between the phase of low-frequency oscillation and amplitude of high-frequency oscillation that appeared in the middle period of the seizures is a reliable biomarker in epileptogenic cortical areas. The modulation index can be used as a good tool for lateralization and localization for the epileptic focus in patients with epilepsy. Phase-amplitude coupling can provide meaningful reference for accurate resection of epileptogenic focus and provide insight into the underlying neural dynamics of the epileptic seizure in patients with temporal lobe epilepsy. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy

PubMed Central

Franco-Villanueva, Ana; Romancheck, Christian; Morano, Rachel L.; Smith, Brittany L.; Packard, Benjamin A.; Danzer, Steve C.; Herman, James P.

2018-01-01

Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy. PMID:29795651

Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy.

PubMed

Wulsin, Aynara C; Franco-Villanueva, Ana; Romancheck, Christian; Morano, Rachel L; Smith, Brittany L; Packard, Benjamin A; Danzer, Steve C; Herman, James P

2018-01-01

Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy.

Evaluating whole genome sequence data from the Genetic Absence Epilepsy Rat from Strasbourg and its related non-epileptic strain

PubMed Central

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

Neural Dynamics Underlying Target Detection in the Human Brain

PubMed Central

Bansal, Arjun K.; Madhavan, Radhika; Agam, Yigal; Golby, Alexandra; Madsen, Joseph R.

2014-01-01

Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses. PMID:24553944

Methodological standards for in vitro models of epilepsy and epileptic seizures. A TASK1-WG4 report of the AES/ILAE Translational Task Force of the ILAE.

PubMed

Raimondo, Joseph V; Heinemann, Uwe; de Curtis, Marco; Goodkin, Howard P; Dulla, Chris G; Janigro, Damir; Ikeda, Akio; Lin, Chou-Ching K; Jiruska, Premysl; Galanopoulou, Aristea S; Bernard, Christophe

2017-11-01

In vitro preparations are a powerful tool to explore the mechanisms and processes underlying epileptogenesis and ictogenesis. In this review, we critically review the numerous in vitro methodologies utilized in epilepsy research. We provide support for the inclusion of detailed descriptions of techniques, including often ignored parameters with unpredictable yet significant effects on study reproducibility and outcomes. In addition, we explore how recent developments in brain slice preparation relate to their use as models of epileptic activity. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Phosphatase inhibitors remove the run-down of γ-aminobutyric acid type A receptors in the human epileptic brain

PubMed Central

Palma, E.; Ragozzino, D. A.; Di Angelantonio, S.; Spinelli, G.; Trettel, F.; Martinez-Torres, A.; Torchia, G.; Arcella, A.; Di Gennaro, G.; Quarato, P. P.; Esposito, V.; Cantore, G.; Miledi, R.; Eusebi, F.

2004-01-01

The properties of γ-aminobutyric acid (GABA) type A receptors (GABAA receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABAA receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat α1β2γ2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABAA receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABAA receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABAA-receptor β1, β2, β3, and γ2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABAA receptors. Blockage of phosphatases stabilizes the TLE GABAA receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy. PMID:15218107

Study on localization of epileptic focus based on causality analysis

NASA Astrophysics Data System (ADS)

Shan, Shaojie; Li, Hanjun; Tang, Xiaoying

2018-05-01

In this paper, we considered that the ECoG signal contain abundant pathological information, which can be used for the localization of epileptic focus before epileptic seizures in 1-2 mins. In order to validate this hypothesis, cutting the ECoG into three stages: before seizure, seizure and after seizure, then through using Granger causality algorithm, PSI causality algorithm, Transfer Entropy causality algorithm at different stages of epilepsy ECoG, we were able to do the causality analysis of ECoG data. The results have shown that there is significant difference with the causality value of the epileptic focus area in before seizure, seizure and after seizure. An increase is in the causality value of each channel during epileptic seizure. After epileptic seizure, the causality between the channels showed a downward trend, but the difference was not obvious. The difference of the causality provides a reliable technical method to assist the clinical diagnosis of epileptic focus.

Source localization of temporal lobe epilepsy using PCA-LORETA analysis on ictal EEG recordings.

PubMed

Stern, Yaki; Neufeld, Miriam Y; Kipervasser, Svetlana; Zilberstein, Amir; Fried, Itzhak; Teicher, Mina; Adi-Japha, Esther

2009-04-01

Localizing the source of an epileptic seizure using noninvasive EEG suffers from inaccuracies produced by other generators not related to the epileptic source. The authors isolated the ictal epileptic activity, and applied a source localization algorithm to identify its estimated location. Ten ictal EEG scalp recordings from five different patients were analyzed. The patients were known to have temporal lobe epilepsy with a single epileptic focus that had a concordant MRI lesion. The patients had become seizure-free following partial temporal lobectomy. A midinterval (approximately 5 seconds) period of ictal activity was used for Principal Component Analysis starting at ictal onset. The level of epileptic activity at each electrode (i.e., the eigenvector of the component that manifest epileptic characteristic), was used as an input for low-resolution tomography analysis for EEG inverse solution (Zilberstain et al., 2004). The algorithm accurately and robustly identified the epileptic focus in these patients. Principal component analysis and source localization methods can be used in the future to monitor the progression of an epileptic seizure and its expansion to other areas.

The antiepileptic effect of Centella asiatica on the activities of Na+/K+, Mg2+ and Ca2+-ATPases in rat brain during pentylenetetrazol–induced epilepsy

PubMed Central

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

Knowledge and attitude of epilepsy among secondary schools students (epileptic and non-epileptic) in Assiut city Egypt.

PubMed

Shehata, Ghaydaa A; Mahran, Dalia G

2011-06-01

This study was designed to assess knowledge and attitude with respect to epilepsy among secondary school students (epileptic and none) in Assiut city, Egypt. A cross sectional study was applied among secondary school students in Assiut city, Egypt. A 13-item questionnaire was self administered by 2226 students who selected randomly. All students either epileptic or non-epileptic had been heard about epilepsy. Only 7.1% of epileptic students and 8.5% of non-epileptic students thought that the epilepsy is a brain disease. Out of 2198 non-epileptic students, 28.4% thought that person with epilepsy (PWE) should not marry and 92% of them refused to marry from PWE. The correct knowledge of epilepsy was significantly positive correlated with positive attitude towards PWE. However, students still feel persons with epilepsy are stigmatized and are different from others. Secondary school students in Egypt have a vague knowledge about the etiology of epilepsy. Misconceptions about and negative attitudes towards epilepsy are unexpectedly high among those students. Copyright © 2011 Elsevier B.V. All rights reserved.

Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.

PubMed

Coughlin, Curtis R; Scharer, Gunter H; Friederich, Marisa W; Yu, Hung-Chun; Geiger, Elizabeth A; Creadon-Swindell, Geralyn; Collins, Abigail E; Vanlander, Arnaud V; Coster, Rudy Van; Powell, Christopher A; Swanson, Michael A; Minczuk, Michal; Van Hove, Johan L K; Shaikh, Tamim H

2015-08-01

Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations in either mitochondrial DNA or POLG are often present, other nuclear defects in mitochondrial DNA replication and protein translation have been associated with a severe epileptic encephalopathy. We identified a proband with an epileptic encephalopathy, complex movement disorder and a combined mitochondrial respiratory chain enzyme deficiency. The child presented with neurological regression, complex movement disorder and intractable seizures. A combined deficiency of mitochondrial complexes I, III and IV was noted in liver tissue, along with increased mitochondrial DNA content in skeletal muscle. Incomplete assembly of complex V, using blue native polyacrylamide gel electrophoretic analysis and complex I, using western blotting, suggested a disorder of mitochondrial transcription or translation. Exome sequencing identified compound heterozygous mutations in CARS2, a mitochondrial aminoacyl-tRNA synthetase. Both mutations affect highly conserved amino acids located within the functional ligase domain of the cysteinyl-tRNA synthase. A specific decrease in the amount of charged mt-tRNA(Cys) was detected in patient fibroblasts compared with controls. Retroviral transfection of the wild-type CARS2 into patient skin fibroblasts led to the correction of the incomplete assembly of complex V, providing functional evidence for the role of CARS2 mutations in disease aetiology. Our findings indicate that mutations in CARS2 result in a mitochondrial translational defect as seen in individuals with mitochondrial epileptic encephalopathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Inhibition of p38 mitogen-activated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats.

PubMed

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.

Frequency domain beamforming of magnetoencephalographic beta band activity in epilepsy patients with focal cortical dysplasia.

PubMed

Heers, Marcel; Hirschmann, Jan; Jacobs, Julia; Dümpelmann, Matthias; Butz, Markus; von Lehe, Marec; Elger, Christian E; Schnitzler, Alfons; Wellmer, Jörg

2014-09-01

Spike-based magnetoencephalography (MEG) source localization is an established method in the presurgical evaluation of epilepsy patients. Focal cortical dysplasias (FCDs) are associated with focal epileptic discharges of variable morphologies in the beta frequency band in addition to single epileptic spikes. Therefore, we investigated the potential diagnostic value of MEG-based localization of spike-independent beta band (12-30Hz) activity generated by epileptogenic lesions. Five patients with FCD IIB underwent MEG. In one patient, invasive EEG (iEEG) was recorded simultaneously with MEG. In two patients, iEEG succeeded MEG, and two patients had MEG only. MEG and iEEG were evaluated for epileptic spikes. Two minutes of iEEG data and MEG epochs with no spikes as well as MEG epochs with epileptic spikes were analyzed in the frequency domain. MEG oscillatory beta band activity was localized using Dynamic Imaging of Coherent Sources. Intralesional beta band activity was coherent between simultaneous MEG and iEEG recordings. Continuous 14Hz beta band power correlated with the rate of interictal epileptic discharges detected in iEEG. In cases where visual MEG evaluation revealed epileptic spikes, the sources of beta band activity localized within <2cm of the epileptogenic lesion as shown on magnetic resonance imaging. This result held even when visually marked epileptic spikes were deselected. When epileptic spikes were detectable in iEEG but not MEG, MEG beta band activity source localization failed. Source localization of beta band activity has the potential to contribute to the identification of epileptic foci in addition to source localization of visually marked epileptic spikes. Thus, this technique may assist in the localization of epileptic foci in patients with suspected FCD. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparing maximum autonomic activity of psychogenic non-epileptic seizures and epileptic seizures using heart rate variability.

PubMed

Jeppesen, Jesper; Beniczky, Sándor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

2016-04-01

The semiology of psychogenic non-epileptic seizures (PNES) can resemble epileptic seizures, and differentiation between epileptic seizures with no EEG-correlate and PNES can be challenging even for trained experts. Therefore, there has been a search for a quantitative measure, other than EEG and semiology that could distinguish PNES from epileptic seizures. We used ECG to measure heart rate variability (HRV) in order to compare maximum autonomic activity of epileptic seizures and PNES. These comparisons could potentially serve as biomarkers for distinguishing these types of clinical episodes. Forty-nine epileptic seizures from 17 patients and 24 PNES from 7 patients with analyzable ECG were recorded during long-term video-EEG monitoring. Moving windows of 100 R-R intervals throughout each seizure were used to find maximum values of Cardiac Sympathetic Index (CSI) (sympathetic tonus) and minimum values of Cardiac Vagal Index (CVI), Root-Mean-Square-of-Successive-Differences (RMSSD) and HF-power (parasympathetic tonus). In addition, non-seizure recordings of each patient were used to compare HRV-parameters between the groups. The maximum CSI for epilepsy seizures were higher than PNES (P=0.015). The minimum CVI, minimum RMSSD and HF-power did not show significant difference between epileptic seizures and PNES (P=0.762; P=0.152; P=0.818). There were no statistical difference of non-seizure HRV-parameters between the PNES and epilepsy patients. We found the maximum sympathetic activity accompanying the epileptic seizures to be higher, than that during the PNES. However, the great variation of autonomic response within both groups makes it difficult to use these HRV-measures as a sole measurement in distinguishing epileptic seizures from PNES. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.

PubMed

Xiang, Yan; Li, Zhi-Xiao; Zhang, Ding-Yu; He, Zhi-Gang; Hu, Ji; Xiang, Hong-Bing

2017-01-01

It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.

Probing voltage sensing domain of KCNQ2 channel as a potential target to combat epilepsy: a comparative study.

PubMed

Mehta, Pakhuri; Srivastava, Shubham; Choudhary, Bhanwar Singh; Sharma, Manish; Malik, Ruchi

2017-12-01

Multidrug resistance along with side-effects of available anti-epileptic drugs and unavailability of potent and effective agents in submicromolar quantities presents the biggest therapeutic challenges in anti-epileptic drug discovery. The molecular modeling techniques allow us to identify agents with novel structures to match the continuous urge for its discovery. KCNQ2 channel represents one of the validated targets for its therapy. The present study involves identification of newer anti-epileptic agents by means of a computer-aided drug design adaptive protocol involving both structure-based virtual screening of Asinex library using homology model of KCNQ2 and 3D-QSAR based virtual screening with docking analysis, followed by dG bind and ligand efficiency calculations with ADMET studies, of which 20 hits qualified all the criterions. The best ligands of both screenings with least potential for toxicity predicted computationally were then taken for molecular dynamic simulations. All the crucial amino acid interactions were observed in hits of both screenings such as Glu130, Arg207, Arg210 and Phe137. Robustness of docking protocol was analyzed through Receiver operating characteristic (ROC) curve values 0.88 (Area under curve AUC = 0.87) in Standard Precision and 0.84 (AUC = 0.82) in Extra Precision modes. Novelty analysis indicates that these compounds have not been reported previously as anti-epileptic agents.

Daytime encopresis associated with gland mal epileptic seizures: case report.

PubMed

Oyatsi, D P

2005-08-01

Sphincteric incontinence of stool and urine are not unusual features of generalised epileptic seizures. Isolated secondary encopresis as a manifestation of an epileptic seizure is unusual. This report is of, a four year old boy, with daytime secondary non-retentive encopresis. The onset of encopresis was preceded by several episodes of nocturnal generalised tonic clonic epileptic seizures. An electroencephalogram showed features consistent with complex partial seizures. He was commenced on anti-epileptic treatment with phenytoin sodium, and by the third day of treatment, the patient had achieved stool control.

Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

PubMed Central

Major, Sebastian; Pannek, Heinz-Wolfgang; Woitzik, Johannes; Scheel, Michael; Wiesenthal, Dirk; Martus, Peter; Winkler, Maren K.L.; Hartings, Jed A.; Fabricius, Martin; Speckmann, Erwin-Josef; Gorji, Ali

2012-01-01

Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating channels initiates spreading depression of brain activity. In contrast, epileptic seizures show modest ion translocation and sustained depolarization below the inactivation threshold for action potential generating channels. Such modest sustained depolarization allows synchronous, highly frequent neuronal firing; ictal epileptic field potentials being its electrocorticographic and epileptic seizure its clinical correlate. Nevertheless, Leão in 1944 and Van Harreveld and Stamm in 1953 described in animals that silencing of brain activity induced by spreading depolarization changed during minimal electrical stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We here report on such spreading convulsions in monopolar subdural recordings in 2 of 25 consecutive aneurismal subarachnoid haemorrhage patients in vivo and neocortical slices from 12 patients with intractable temporal lobe epilepsy in vitro. The in vitro results suggest that γ-aminobutyric acid-mediated inhibition protects from spreading convulsions. Moreover, we describe arterial pulse artefacts mimicking epileptic field potentials in three patients with subarachnoid haemorrhage that ride on the slow potential peak. Twenty-one of the 25 subarachnoid haemorrhage patients (84%) had 656 spreading depolarizations in contrast to only three patients (12%) with 55 ictal epileptic events isolated from spreading depolarizations. Spreading depolarization frequency and depression periods per 24 h recording episodes showed an early and a delayed peak on Day 7. Patients surviving subarachnoid haemorrhage with poor outcome at 6 months showed significantly higher total and peak numbers of spreading depolarizations and significantly longer total and peak depression periods during the electrocorticographic monitoring than patients with good outcome. In a semi-structured telephone interview 3 years after the initial haemorrhage, 44% of the subarachnoid haemorrhage survivors had developed late post-haemorrhagic seizures requiring anti-convulsant medication. In those patients, peak spreading depolarization number had been significantly higher [15.1 (11.4–30.8) versus 7.0 (0.8–11.2) events per day, P = 0.045]. In summary, monopolar recordings here provided unequivocal evidence of spreading convulsions in patients. Hence, practically all major pathological cortical network events in animals have now been observed in people. Early spreading depolarizations may indicate a risk for late post-haemorrhagic seizures. PMID:22120143

Behavioral alterations in the pilocarpine model of temporal lobe epilepsy in mice.

PubMed

Gröticke, Ina; Hoffmann, Katrin; Löscher, Wolfgang

2007-10-01

Psychiatric disorders frequently occur in patients with epilepsy, but the relationship between epilepsy and psychopathology is poorly understood. Frequent comorbidities in epilepsy patients comprise major depression, anxiety disorders, psychosis and cognitive dysfunction. Animal models of epilepsy, such as the pilocarpine model of acquired epilepsy, are useful to study the relationship between epilepsy and behavioral dysfunctions. However, despite the advantages of mice in studying the genetic underpinning of behavioral alterations in epilepsy, mice have only rarely been used to characterize behavioral correlates of epilepsy. This prompted us to study the behavioral and cognitive alterations developing in NMRI mice in the pilocarpine model of epilepsy, using an anxiety test battery as well as tests for depression, drug-induced psychosis, spatial memory, and motor functions. In order to ensure the occurrence of status epilepticus (SE) and decrease mortality, individual dosing of pilocarpine was performed by ramping up the dose until onset of SE. This protocol was used for studying the consequences of SE, i.e. hippocampal damage, incidence of epilepsy with spontaneous recurrent seizures, and behavioral alterations. SE was terminated by diazepam after either 60, 90 or 120 min. All mice that survived SE developed epilepsy, but the severity of hippocampal damage varied depending on SE length. In all anxiety tests, except the elevated plus maze test, epileptic mice exhibited significant increases of anxiety-related behavior. Surprisingly, a decrease in depression-like behavior was observed in the forced swimming and tail suspension tests. Furthermore, epileptic mice were less sensitive than controls to most of the behavioral effects induced by MK-801 (dizocilpine). Learning and memory were impaired in epileptic mice irrespective of SE duration. Thus, the pilocarpine-treated mice seem to reflect several of the behavioral and cognitive disturbances that are associated with epilepsy in humans. This makes these animals an ideal model to study the neurobiological mechanisms underlying the association between epilepsy and psychopathology.

[Occupational health problems in epileptics].

PubMed

Romankow, Jacek

2005-01-01

From the point of view of occupational medicine some questions are important for epileptics; amongst others: falling, behavior during the paroxysm, shift work dependence of attack, behaviour after an epileptic episode. Occupational capacity depends on the process of epileptic episodes and their frequency. The development of neurology has rendered numerous cures from epilepsy, but the the occupational stigma is difficult in many professions--electrical engineering, working with machinery, milling machines and others. In some professions a care must be taken when hiring epileptics--for instance professions with a fall hazard, jobs connected with public transport or involving crane or excavator operation.

Epileptic seizure detection in EEG signal with GModPCA and support vector machine.

PubMed

Jaiswal, Abeg Kumar; Banka, Haider

2017-01-01

Epilepsy is one of the most common neurological disorders caused by recurrent seizures. Electroencephalograms (EEGs) record neural activity and can detect epilepsy. Visual inspection of an EEG signal for epileptic seizure detection is a time-consuming process and may lead to human error; therefore, recently, a number of automated seizure detection frameworks were proposed to replace these traditional methods. Feature extraction and classification are two important steps in these procedures. Feature extraction focuses on finding the informative features that could be used for classification and correct decision-making. Therefore, proposing effective feature extraction techniques for seizure detection is of great significance. Principal Component Analysis (PCA) is a dimensionality reduction technique used in different fields of pattern recognition including EEG signal classification. Global modular PCA (GModPCA) is a variation of PCA. In this paper, an effective framework with GModPCA and Support Vector Machine (SVM) is presented for epileptic seizure detection in EEG signals. The feature extraction is performed with GModPCA, whereas SVM trained with radial basis function kernel performed the classification between seizure and nonseizure EEG signals. Seven different experimental cases were conducted on the benchmark epilepsy EEG dataset. The system performance was evaluated using 10-fold cross-validation. In addition, we prove analytically that GModPCA has less time and space complexities as compared to PCA. The experimental results show that EEG signals have strong inter-sub-pattern correlations. GModPCA and SVM have been able to achieve 100% accuracy for the classification between normal and epileptic signals. Along with this, seven different experimental cases were tested. The classification results of the proposed approach were better than were compared the results of some of the existing methods proposed in literature. It is also found that the time and space complexities of GModPCA are less as compared to PCA. This study suggests that GModPCA and SVM could be used for automated epileptic seizure detection in EEG signal.

Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma

PubMed Central

Engel, Tobias; Murphy, Brona M.; Hatazaki, Seiji; Jimenez-Mateos, Eva M.; Concannon, Caoimhin G.; Woods, Ina; Prehn, Jochen H. M.; Henshall, David C.

2010-01-01

The functional significance of neuronal death for pathogenesis of epilepsy and the underlying molecular mechanisms thereof remain incompletely understood. The p53 transcription factor has been implicated in seizure damage, but its target genes and the influence of cell death under its control on epilepsy development are unknown. In the present study, we report that status epilepticus (SE) triggered by intra-amygdala kainic acid in mice causes rapid p53 accumulation and subsequent hippocampal damage. Expression of p53-up-regulated mediator of apoptosis (Puma), a proapoptotic Bcl-2 homology domain 3-only protein under p53 control, was increased within a few hours of SE. Induction of Puma was blocked by pharmacologic inhibition of p53, and hippocampal damage was also reduced. Puma induction was also blocked in p53-deficient mice subject to SE. Compared to Puma-expressing mice, Puma-deficient mice had significantly smaller hippocampal lesions after SE. Long-term, continuous telemetric EEG monitoring revealed a ∼60% reduction in the frequency of epileptic seizures in the Puma-deficient mice compared to Puma-expressing mice. These are the first data showing genetic deletion of a proapoptotic protein acting acutely to influence neuronal death subsequently alters the phenotype of epilepsy in the long-term, supporting the concept that apoptotic pathway activation is a trigger of epileptogenesis.—Engel, T., Murphy, B. M., Hatazaki, S., Jimenez-Mateos, E. M., Concannon, C. G., Woods, I., Prehn, J. H. M., Henshall, D. C. Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma. PMID:19890018

SPECT measurements with /sup 99m/Tc-HM-PAO in focal epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryding, E.; Rosen, I.; Elmqvist, D.

1988-12-01

The ability of SPECT measurements with (/sup 99m/Tc)-HM-PAO (Ceretec) to find the location of the epileptic focus was studied in patients under consideration for neurosurgical treatment for therapy-resistant focal epilepsy. The location of low (/sup 99m/Tc)-HM-PAO uptake regions found at interictal measurements, and of high (/sup 99m/Tc)-HM-PAO uptake regions found at ictal measurements, was compared to the findings of extensive ictal and interictal EEG examinations, and to the results of CT and MRT. While EEG revealed focal epileptic activity in all of the 14 patients, SPECT showed regional abnormalities in 13 (93%). CT and MRT showed abnormal findings in 30%.

The quantitative measurement of consciousness during epileptic seizures.

PubMed

Nani, Andrea; Cavanna, Andrea E

2014-01-01

The assessment of consciousness is a fundamental element in the classification of epileptic seizures. It is, therefore, of great importance for clinical practice to develop instruments that enable an accurate and reliable measurement of the alteration of consciousness during seizures. Over the last few years, three psychometric scales have been specifically proposed to measure ictal consciousness: the Ictal Consciousness Inventory (ICI), the Consciousness Seizure Scale (CSS), and the Responsiveness in Epilepsy Scale--versions I and II (RES-I and RES-II). The ICI is a self-report psychometric instrument which retrospectively assesses ictal consciousness along the dimensions of the level/arousal and contents/awareness. The CSS has been used by clinicians to quantify the impairment of consciousness in order to establish correlations with the brain mechanisms underlying alterations of consciousness during temporal lobe seizures. The most recently developed observer-rated instrument is the RES-I, which has been used to assess responsiveness during epileptic seizures in patients undergoing video-EEG. The implementation of standardized psychometric tools for the assessment of ictal consciousness can complement clinical observations and contribute to improve accuracy in seizure classification. © 2013.

Nonlinear analysis of EEG for epileptic seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hively, L.M.; Clapp, N.E.; Daw, C.S.

1995-04-01

We apply chaotic time series analysis (CTSA) to human electroencephalogram (EEG) data. Three epoches were examined: epileptic seizure, non-seizure, and transition from non-seizure to seizure. The CTSA tools were applied to four forms of these data: raw EEG data (e-data), artifact data (f-data) via application of a quadratic zero-phase filter of the raw data, artifact-filtered data (g- data) and that was the residual after subtracting f-data from e-data, and a low-pass-filtered version (h-data) of g-data. Two different seizures were analyzed for the same patient. Several nonlinear measures uniquely indicate an epileptic seizure in both cases, including an abrupt decrease inmore » the time per wave cycle in f-data, an abrupt increase in the Kolmogorov entropy and in the correlation dimension for e-h data, and an abrupt increase in the correlation dimension for e-h data. The transition from normal to seizure state also is characterized by distinctly different trends in the nonlinear measures for each seizure and may be potential seizure predictors for this patient. Surrogate analysis of e-data shows that statistically significant nonlinear structure is present during the non-seizure, transition , and seizure epoches.« less

Dynamic analysis of heartbeat rate signals of epileptics using multidimensional phase space reconstruction approach

NASA Astrophysics Data System (ADS)

Su, Zhi-Yuan; Wu, Tzuyin; Yang, Po-Hua; Wang, Yeng-Tseng

2008-04-01

The heartbeat rate signal provides an invaluable means of assessing the sympathetic-parasympathetic balance of the human autonomic nervous system and thus represents an ideal diagnostic mechanism for detecting a variety of disorders such as epilepsy, cardiac disease and so forth. The current study analyses the dynamics of the heartbeat rate signal of known epilepsy sufferers in order to obtain a detailed understanding of the heart rate pattern during a seizure event. In the proposed approach, the ECG signals are converted into heartbeat rate signals and the embedology theorem is then used to construct the corresponding multidimensional phase space. The dynamics of the heartbeat rate signal are then analyzed before, during and after an epileptic seizure by examining the maximum Lyapunov exponent and the correlation dimension of the attractors in the reconstructed phase space. In general, the results reveal that the heartbeat rate signal transits from an aperiodic, highly-complex behaviour before an epileptic seizure to a low dimensional chaotic motion during the seizure event. Following the seizure, the signal trajectories return to a highly-complex state, and the complex signal patterns associated with normal physiological conditions reappear.

Multiphoton fluorescence imaging of NADH to quantify metabolic changes in epileptic tissue in vitro

NASA Astrophysics Data System (ADS)

Chia, Thomas H.; Zinter, Joseph; Spencer, Dennis D.; Williamson, Anne; Levene, Michael J.

2007-02-01

A powerful advantage of multiphoton microscopy is its ability to image endogenous fluorophores such as the ubiquitous coenzyme NADH in discrete cellular populations. NADH is integral in both oxidative and non-oxidative cellular metabolism. NADH loses fluorescence upon oxidation to NAD +; thus changes in NADH fluorescence can be used to monitor metabolism. Recent studies have suggested that hypo metabolic astrocytes play an important role in cases of temporal lobe epilepsy (TLE). Current theories suggest this may be due to defective and/or a reduced number of mitochondria or dysfunction of the neuronal-astrocytic metabolic coupling. Measuring NADH fluorescence changes following chemical stimulation enables the quantification of the cellular distribution of metabolic anomalies in epileptic brain tissue compared to healthy tissue. We present what we believe to be the first multiphoton microscopy images of NADH from the human brain. We also present images of NADH fluorescence from the hippocampus of the kainate-treated rat TLE model. In some experiments, human and rat astrocytes were selectively labeled with the fluorescent dye sulforhodamine 101 (SR101). Our results demonstrate that multiphoton microscopy is a powerful tool for assaying the metabolic pathologies associated with temporal lobe epilepsy in humans and in rodent models.

Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

PubMed

Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

2014-11-05

Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy

PubMed Central

Kovačević, Jovana; Maroteaux, Gregoire; Schut, Desiree; Loos, Maarten; Dubey, Mohit; Pitsch, Julika; Remmelink, Esther; Koopmans, Bastijn; Crowley, James; Cornelisse, L Niels; Sullivan, Patrick F; Schoch, Susanne; Toonen, Ruud F; Stiedl, Oliver; Verhage, Matthijs

2018-01-01

Abstract De novo heterozygous mutations in STXBP1/Munc18-1 cause early infantile epileptic encephalopathies (EIEE4, OMIM #612164) characterized by infantile epilepsy, developmental delay, intellectual disability, and can include autistic features. We characterized the cellular deficits for an allelic series of seven STXBP1 mutations and developed four mouse models that recapitulate the abnormal EEG activity and cognitive aspects of human STXBP1-encephalopathy. Disease-causing STXBP1 variants supported synaptic transmission to a variable extent on a null background, but had no effect when overexpressed on a heterozygous background. All disease variants had severely decreased protein levels. Together, these cellular studies suggest that impaired protein stability and STXBP1 haploinsufficiency explain STXBP1-encephalopathy and that, therefore, Stxbp1+/− mice provide a valid mouse model. Simultaneous video and EEG recordings revealed that Stxbp1+/− mice with different genomic backgrounds recapitulate the seizure/spasm phenotype observed in humans, characterized by myoclonic jerks and spike-wave discharges that were suppressed by the antiepileptic drug levetiracetam. Mice heterozygous for Stxbp1 in GABAergic neurons only, showed impaired viability, 50% died within 2–3 weeks, and the rest showed stronger epileptic activity. c-Fos staining implicated neocortical areas, but not other brain regions, as the seizure foci. Stxbp1+/− mice showed impaired cognitive performance, hyperactivity and anxiety-like behaviour, without altered social behaviour. Taken together, these data demonstrate the construct, face and predictive validity of Stxbp1+/− mice and point to protein instability, haploinsufficiency and imbalanced excitation in neocortex, as the underlying mechanism of STXBP1-encephalopathy. The mouse models reported here are valid models for development of therapeutic interventions targeting STXBP1-encephalopathy. PMID:29538625

Functional neuroimaging in epileptic encephalopathies.

PubMed

Siniatchkin, Michael; Capovilla, Giuseppe

2013-11-01

Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive disability in EEs remain unclear. This review summarized neuroimaging studies that have tried to describe specific fingerprints of brain activation in EE. Although the epileptic activity can be generated individually in different brain regions, it seems likely that the activity propagates in a syndrome-specific way. In some EEs, the epileptiform discharges were associated with an interruption of activity in the default mode network. In another EE, other mechanisms seem to underlie cognitive disability associated with epileptic activity, for example, abnormal connectivity pattern or interfering activity in the thalamocortical network. Further neuroimaging studies are needed to investigate the short-term and long-term impact of epileptic activity on cognition and development. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

A novel scheme for the validation of an automated classification method for epileptic spikes by comparison with multiple observers.

PubMed

Sharma, Niraj K; Pedreira, Carlos; Centeno, Maria; Chaudhary, Umair J; Wehner, Tim; França, Lucas G S; Yadee, Tinonkorn; Murta, Teresa; Leite, Marco; Vos, Sjoerd B; Ourselin, Sebastien; Diehl, Beate; Lemieux, Louis

2017-07-01

To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data. Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs. First, we determined whether WC-human agreement variability falls within inter-reviewer agreement variability by calculating the variation of information for each classifier pair and quantifying the overlap between all WC-reviewer and all reviewer-reviewer pairs. Second, we compared WC and EEG reviewers' spike identification and individual spike class labels visually and quantitatively. The overlap between all WC-human pairs and all human pairs was >80% for 3/5 patients and >58% for the other 2 patients demonstrating WC falling within inter-human variation. The average sensitivity of spike marking for WC was 91% and >87% for all three EEG reviewers. Finally, there was a strong visual and quantitative similarity between WC and EEG reviewers. WC performance is indistinguishable to that of EEG reviewers' suggesting it could be a valid clinical tool for the assessment of IEDs. WC can be used to provide quantitative analysis of epileptic spikes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Oxidative Stress Measurement and Prediction of Epileptic Seizure in Children and Adults With Severe Motor and Intellectual Disabilities

PubMed Central

Morimoto, Masahito; Satomura, Shigeko; Hashimoto, Toshiaki; Ito, Etsuro; Kyotani, Shojiro

2016-01-01

Background The medical care of severe motor and intellectual disabilities (SMID) depends on the empirical medical care. Epileptic seizure specific to SMID is difficult to suppress using anti-epileptic drugs, and its tendency to persist for long periods poses an issue. The present study was undertaken to evaluate the relationship between epileptic seizure in cases with SMID and oxidative stress in the living body by examining endogenous antioxidants, the degree of oxidation (reactive oxygen metabolites (d-ROMs)), and the biological antioxidant potential (BAP) as indicators. Methods Target patients were 43 SMID epilepsy patients. Blood was sampled before breakfast and medication. As for the specimen, d-ROMs and BAP were measured using the free radical analyzer. Results The present study did not reveal any correlation between endogenous antioxidants (albumin) and the frequency of epileptic seizures. On the other hand, d-ROMs were correlated with the frequency of epileptic seizure. In particular, strong correlations between the frequency of epileptic seizures and the d-ROMs/BAP ratio as well as the BAP/d-ROMs ratio were noted. Conclusions These results indicate that the use of d-ROMs and BAP as biomarkers can provide a tool for predicting the prognosis of epileptic seizures in patients with SMID. PMID:27222671

Oxidative Stress Measurement and Prediction of Epileptic Seizure in Children and Adults With Severe Motor and Intellectual Disabilities.

PubMed

Morimoto, Masahito; Satomura, Shigeko; Hashimoto, Toshiaki; Ito, Etsuro; Kyotani, Shojiro

2016-06-01

The medical care of severe motor and intellectual disabilities (SMID) depends on the empirical medical care. Epileptic seizure specific to SMID is difficult to suppress using anti-epileptic drugs, and its tendency to persist for long periods poses an issue. The present study was undertaken to evaluate the relationship between epileptic seizure in cases with SMID and oxidative stress in the living body by examining endogenous antioxidants, the degree of oxidation (reactive oxygen metabolites (d-ROMs)), and the biological antioxidant potential (BAP) as indicators. Target patients were 43 SMID epilepsy patients. Blood was sampled before breakfast and medication. As for the specimen, d-ROMs and BAP were measured using the free radical analyzer. The present study did not reveal any correlation between endogenous antioxidants (albumin) and the frequency of epileptic seizures. On the other hand, d-ROMs were correlated with the frequency of epileptic seizure. In particular, strong correlations between the frequency of epileptic seizures and the d-ROMs/BAP ratio as well as the BAP/d-ROMs ratio were noted. These results indicate that the use of d-ROMs and BAP as biomarkers can provide a tool for predicting the prognosis of epileptic seizures in patients with SMID.

Sudden death in epileptic rats exposed to nocturnal magnetic fields that simulate the shape and the intensity of sudden changes in geomagnetic activity: an experiment in response to Schnabel, Beblo and May

NASA Astrophysics Data System (ADS)

Persinger, M. A.; McKay, B. E.; O'Donovan, C. A.; Koren, S. A.

2005-03-01

To test the hypothesis that sudden unexplained death (SUD) in some epileptic patients is related to geomagnetic activity we exposed rats in which limbic epilepsy had been induced to experimentally produced magnetic fields designed to simulate sudden storm commencements (SSCs). Prior studies with rats had shown that sudden death in groups of rats in which epilepsy had been induced months earlier was associated with the occurrence of SSCs and increased geomagnetic activity during the previous night. Schnabel et al. [(2000) Neurology 54:903 908) found no relationship between SUD in human patients and geomagnetic activity. A total of 96 rats were exposed to either 500, 50, 10 40 nT or sham (less than 10 nT) magnetic fields for 6 min every hour between midnight and 0800 hours (local time) for three successive nights. The shape of the complex, amplitude-modulated magnetic fields simulated the shape and structure of an average SSC. The rats were then seized with lithium and pilocarpine and the mortality was monitored. Whereas 10% of the rats that had been exposed to the sham field died within 24 h, 60% of the rats that had been exposed to the experimental magnetic fields simulating natural geomagnetic activity died (P<.001) during this period. These results suggest that correlational analyses between SUD in epileptic patients and increased geomagnetic activity can be simulated experimentally in epileptic rats and that potential mechanisms might be testable directly.

Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD).

PubMed

Yasuhara, Akihiro

2010-11-01

Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality. Purposes of this study are the confirmation of incidence of epileptic seizures and EEG abnormalities in children with autism using a high performance digital EEG, to examine the nature of EEG abnormalities such as locus or modality, and to determine if the development of children with ASD, who have experienced developmental delay, improves when their epilepsy has been treated and maintained under control. A total of 1014 autistic children that have been treated and followed-up for more than 3 years at Yasuhara Children's Clinic in Osaka, Japan, were included in this study. Each participant's EEG had been recorded approximately every 6 months under sleep conditions. Epilepsy was diagnosed in 37% (375/1014) of the study participants. Almost all patients diagnosed with epilepsy presented with symptomatic epilepsy. The data showed that the participants with lower IQ had a higher incidence of epileptic seizures. Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was also a very high incidence of spike discharges in participants whose intellectual quotient was very low or low. Epileptic seizure waves most frequently developed from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of spike discharges in other locations, including temporal lobe (T3, T4, T5, T6), parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was less than 10%. These results support the notion that there is a relationship between ASD and dysfunction of the mirror neuron system. The management of seizure waves in children diagnosed with ASD may result in improves function and reduction of autistic symptoms. Copyright © 2010 Elsevier B.V. All rights reserved.

The origin of the concept of partial epilepsy.

PubMed

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.

Directed differential connectivity graph of interictal epileptiform discharges

PubMed Central

Amini, Ladan; Jutten, Christian; Achard, Sophie; David, Olivier; Soltanian-Zadeh, Hamid; Hossein-Zadeh, Gh. Ali; Kahane, Philippe; Minotti, Lorella; Vercueil, Laurent

2011-01-01

In this paper, we study temporal couplings between interictal events of spatially remote regions in order to localize the leading epileptic regions from intracerebral electroencephalogram (iEEG). We aim to assess whether quantitative epileptic graph analysis during interictal period may be helpful to predict the seizure onset zone of ictal iEEG. Using wavelet transform, cross-correlation coefficient, and multiple hypothesis test, we propose a differential connectivity graph (DCG) to represent the connections that change significantly between epileptic and non-epileptic states as defined by the interictal events. Post-processings based on mutual information and multi-objective optimization are proposed to localize the leading epileptic regions through DCG. The suggested approach is applied on iEEG recordings of five patients suffering from focal epilepsy. Quantitative comparisons of the proposed epileptic regions within ictal onset zones detected by visual inspection and using electrically stimulated seizures, reveal good performance of the present method. PMID:21156385

Gap junction networks can generate both ripple-like and fast ripple-like oscillations

PubMed Central

Simon, Anna; Traub, Roger D.; Vladimirov, Nikita; Jenkins, Alistair; Nicholson, Claire; Whittaker, Roger G.; Schofield, Ian; Clowry, Gavin J.; Cunningham, Mark O.; Whittington, Miles A.

2014-01-01

Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to ‘ordinary’ (slower) ripples. We performed network simulations with model pyramidal neurons, having axons electrically coupled. Ripples (< 250 Hz) were favored when conduction of action potentials, axon to axon, was reliable. Whereas ripple population activity was periodic, firing of individual axons varied in relative phase. A switch from ripples to FRs took place when an ectopic spike occurred in a cell coupled to another cell, itself multiply coupled to others. Propagation could then start in one direction only, a condition suitable for re-entry. The resulting oscillations were > 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between immature neocortical pyramidal cells), then this prediction is testable. PMID:24118191

Seroprevalence and risk factors of human cysticercosis and taeniasis prevalence in a highly endemic area of epilepsy in Bangoua, west Cameroon.

PubMed

Nkouawa, Agathe; Dschanou, Armel Romeo; Moyou-Somo, Roger; Sako, Yasuhito; Ito, Akira

2017-01-01

Cysticercosis caused by the larvae of Taenia solium is a serious and emerging threat to public health in the endemic areas as well as in the non-endemic areas.　Neurocysticercosis, an affection of the central nervous system is a leading cause of epilepsy in endemic areas. This study was carried out to investigate human cysticercosis, taeniasis and risk factors, and also their association with epilepsy in Bangoua, west Cameroon where epilepsy is highly prevalent. Out of 384 people investigated, 12 (3.1%) exhibited antibody response against low molecular weight antigens of T. solium by ELISA. Immunoblot revealed that six persons (1.6%) were seropositive with the same antigens. Among 61 epileptic patients, only one was seropositive by immunoblot and the study did not find any statistically significant difference (P>0.05) in seropositivity to T. solium between epileptic persons (1/61, 1.6%) and non-epileptic group (5/323, 1.5%). In addition, cysticercosis was associated with households eating pork meat from pigs slaughtered at home, but not with other factors. The risk factors including pig farming, the consumption of pork meat, vegetables, and non-drinkable water were attenuated by the relatively good hygiene and pig husbandry practices of the population. No egg of Taenia was found in stool by microscopic examination. All data obtained in this study suggested that cysticercosis might not be the principal causative agent of epilepsy in this area. Copyright © 2015 Elsevier B.V. All rights reserved.

Gap junction networks can generate both ripple-like and fast ripple-like oscillations.

PubMed

Simon, Anna; Traub, Roger D; Vladimirov, Nikita; Jenkins, Alistair; Nicholson, Claire; Whittaker, Roger G; Schofield, Ian; Clowry, Gavin J; Cunningham, Mark O; Whittington, Miles A

2014-01-01

Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to 'ordinary' (slower) ripples. We performed network simulations with model pyramidal neurons, having axons electrically coupled. Ripples (< 250 Hz) were favored when conduction of action potentials, axon to axon, was reliable. Whereas ripple population activity was periodic, firing of individual axons varied in relative phase. A switch from ripples to FRs took place when an ectopic spike occurred in a cell coupled to another cell, itself multiply coupled to others. Propagation could then start in one direction only, a condition suitable for re-entry. The resulting oscillations were > 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between immature neocortical pyramidal cells), then this prediction is testable. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Patient-specific connectivity pattern of epileptic network in frontal lobe epilepsy

PubMed Central

Luo, Cheng; An, Dongmei; Yao, Dezhong; Gotman, Jean

2014-01-01

There is evidence that focal epilepsy may involve the dysfunction of a brain network in addition to the focal region. To delineate the characteristics of this epileptic network, we collected EEG/fMRI data from 23 patients with frontal lobe epilepsy. For each patient, EEG/fMRI analysis was first performed to determine the BOLD response to epileptic spikes. The maximum activation cluster in the frontal lobe was then chosen as the seed to identify the epileptic network in fMRI data. Functional connectivity analysis seeded at the same region was also performed in 63 healthy control subjects. Nine features were used to evaluate the differences of epileptic network patterns in three connection levels between patients and controls. Compared with control subjects, patients showed overall more functional connections between the epileptogenic region and the rest of the brain and higher laterality. However, the significantly increased connections were located in the neighborhood of the seed, but the connections between the seed and remote regions actually decreased. Comparing fMRI runs with interictal epileptic discharges (IEDs) and without IEDs, the patient-specific connectivity pattern was not changed significantly. These findings regarding patient-specific connectivity patterns of epileptic networks in FLE reflect local high connectivity and connections with distant regions differing from those of healthy controls. Moreover, the difference between the two groups in most features was observed in the strictest of the three connection levels. The abnormally high connectivity might reflect a predominant attribute of the epileptic network, which may facilitate propagation of epileptic activity among regions in the network. PMID:24936418

Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

PubMed

Mathew, Jobin; Paul, Jes; Nandhu, M S; Paulose, C S

2010-09-01

We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system. Copyright (c) 2010 Elsevier B.V. All rights reserved.

The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

PubMed

Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

2015-07-01

Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative study of nonlinear properties of EEG signals of normal persons and epileptic patients

PubMed Central

2009-01-01

Background Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak et al. [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusion In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation. PMID:19619290

Epileptic peri-ictal psychosis, a reversible cause of psychosis.

PubMed

González Mingot, C; Gil Villar, M P; Calvo Medel, D; Corbalán Sevilla, T; Martínez Martínez, L; Iñiguez Martínez, C; Santos Lasaosa, S; Mauri Llerda, J A

2013-03-01

Epileptic psychoses are categorised as peri-ictal and interictal according to their relationship with the occurrence of seizures. There is a close temporal relationship between peri-ictal psychosis and seizures, and psychosis may present before (preictal), during (ictal) or after seizures (postictal). Epileptic psychoses usually have acute initial and final phases, with a short symptom duration and complete remission with a risk of recurrence. There is no temporal relationship between interictal or chronic psychosis and epileptic seizures. Another type of epileptic psychosis is related to the response to epilepsy treatment: epileptic psychosis caused by the phenomenon of forced normalisation (alternative psychosis), which includes epileptic psychosis secondary to epilepsy surgery. Although combination treatment with antiepileptic and neuroleptic drugs is now widely used to manage this condition, there are no standard treatment guidelines for epileptic psychosis. We present 5 cases of peri-ictal epileptic psychosis in which we observed an excellent response to treatment with levetiracetam. Good control was achieved over both seizures and psychotic episodes. Levetiracetam was used in association with neuroleptic drugs with no adverse effects, and our patients did not require high doses of the latter. Categorising psychotic states associated with epilepsy according to their temporal relationship with seizures is clinically and prognostically useful because it provides important information regarding disease treatment and progression. The treatment of peri-ictal or acute mental disorders is based on epileptic seizure control, while the treatment of interictal or chronic disorders has more in common with managing disorders which are purely psychiatric in origin. In addition to improving the patient's quality of life and reducing disability, achieving strict control over seizures may also prevent the development of interictal psychosis. For this reason, we believe that establishing a treatment protocol for such cases is necessary. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A.

PubMed

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.

Recording epileptic activity with MEG in a light-weight magnetic shield.

PubMed

De Tiège, Xavier; Op de Beeck, Marc; Funke, Michael; Legros, Benjamin; Parkkonen, Lauri; Goldman, Serge; Van Bogaert, Patrick

2008-12-01

Ten patients with focal epilepsy were studied with magnetoencephalography (MEG) to determine if a new light-weight magnetically shielded room (lMSR) provides sufficient attenuation of magnetic interference to detect and localize the magnetic correlates of epileptic activity. Interictal MEG epileptic events co-localizing with the presumed location of the epileptogenic zone were found in all patients. MEG measurements performed in the lMSR provide an adequate signal-to-noise ratio for non-invasive localization of epileptic foci.

Nocturnal acute laryngospasm in children: a possible epileptic phenomenon.

PubMed

Cohen, H A; Ashkenazi, A; Barzilai, A; Lahat, E

2000-03-01

Respiratory difficulties are not uncommon during epileptic activity in all age groups. Laryngospasm, as an isolated manifestation of epileptic disorder, is a rare phenomenon described previously in only two patients. We report our experience with five children in whom nocturnal laryngospasm was the only clinical manifestation of their epileptic disorder. All children underwent extensive workup and the diagnosis was made by sleep-deprived electroencephalography (two cases) and sleep study (three cases). All patients were treated with carbamezapine with prompt resolution of their laryngospasm.

A species dependent response to the pro-epileptic drug pentylentetrazole in birds.

PubMed

Amin, Faiq; Dar, Asim H; Osama, Khan; Khan, Faezah; Mitha, Rida; Tharwani, Arsal; Haider, Ghulam; Chand, Prem; Arain, Fazal M

2017-09-01

Epilepsy is common disorder that affects over 50 million people worldwide. Birds remain a promising yet largely under-explored model of epilepsy. This study reports the comparison of the response of two species of birds, Australian Parrots (APs) and Sparrows (SPs), to a pro-epileptic drug, Pentylenetetrazole (PTZ). PTZ injections caused myoclonic jerks (MCJs) and tonic clonic seizures (TCSs) in both species. The frequency of MCJs in APs was greater at the dose of 75mg/kg compared to both 50mg/kg and 25mg/kg while it was not significantly different in SPs. The comparison of APs and SPs showed that the frequency of MCJs was greater in APs compared to SPs at 25mg/kg and 75mg/kg while its latency was reduced at 25mg/kg and 50mg/kg. Interestingly SPs had a reduced latency of TCSs compared to APs at 75mg/kg. Glutamatergic and Gabaergic cell count was conducted to determine an association with the epileptic response to PTZ. The Glutamatergic cell counts for SPs was significantly greater than APs and conversely the Gabaergic cell counts in APs was higher compared to SPs. The reason for this difference in findings needs to be further investigated. This study shows that birds, and APs and SPs in particular, are a valid, interesting and under-explored model of epilepsy that should be further explored in order to understand the mysteries of epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Occurrence and clinical features of epileptic and non-epileptic paroxysmal events in five children with Pallister–Killian syndrome

PubMed Central

Filloux, Francis M.; Carey, John C.; Krantz, Ian D.; Ekstrand, Jeffrey J.; Candee, Meghan S.

2013-01-01

Pallister–Killian syndrome (PKS) is a rare, sporadic genetic disorder caused by tetrasomy 12p mosaicism associated with a supernumerary isochromosome. Craniofacial dysmorphism, learning impairment and seizures are considered characteristic. However, little is known of the seizure and epilepsy patterns seen in PKS. To better define the occurrence and nature of epileptic and non-epileptic paroxysmal events in PKS, we describe our experience with 5 patients and compare their features with data from a larger cohort of PKS patients ascertained via a web-based parental questionnaire. Three of the 5 patients have had definite epileptic seizures, and one other has had paroxysmal events as yet not clarified. Four of the 5 have also had either non-epileptic paroxysmal events or episodes of uncertain nature. In those with epilepsy, all have had some period of relatively refractory seizures, all have required more than one antiepileptic drug, but none experienced status epilepticus. Only one of the patients with epilepsy (the oldest) has gone into remission. In two of the four with non-epileptic events, video-electroencephalographic monitoring has been valuable in clarifying the nature of the events. EEG characteristics include a slow dominant frequency as well as generalized and focal epileptiform features. Brain MRI findings can be normal but are variable. These specific findings correspond well to information reported by parents in a larger cohort of 51 individuals with PKS. Better understanding of the nature of epileptic and non-epileptic events in PKS will result from a more detailed analysis of objective data obtained from this larger cohort, and from deeper understanding of the molecular impact of 12p tetrasomy in selected cell lines. PMID:22349688

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.

PubMed

Johnson, Michael R; Shkura, Kirill; Langley, Sarah R; Delahaye-Duriez, Andree; Srivastava, Prashant; Hill, W David; Rackham, Owen J L; Davies, Gail; Harris, Sarah E; Moreno-Moral, Aida; Rotival, Maxime; Speed, Doug; Petrovski, Slavé; Katz, Anaïs; Hayward, Caroline; Porteous, David J; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Starr, John M; Liewald, David C; Visconti, Alessia; Falchi, Mario; Bottolo, Leonardo; Rossetti, Tiziana; Danis, Bénédicte; Mazzuferi, Manuela; Foerch, Patrik; Grote, Alexander; Helmstaedter, Christoph; Becker, Albert J; Kaminski, Rafal M; Deary, Ian J; Petretto, Enrico

2016-02-01

Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.

Impaired Consciousness in Epilepsy

PubMed Central

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

Low-frequency repetitive transcranial magnetic simulation prevents chronic epileptic seizure

PubMed Central

Wang, Yinxu; Wang, Xiaoming; Ke, Sha; Tan, Juan; Hu, Litian; Zhang, Yaodan; Cui, Wenjuan

2013-01-01

Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcranial magnetic simulation on changes in several nonlinear dynamic electroence-phalographic parameters in rats with chronic epilepsy and explored the mechanism underlying petitive transcranial magnetic simulation-induced antiepileptic effects. An epilepsy model was es-tablished using lithium-pilocarpine intraperitoneal injection into adult Sprague-Dawley rats, which were then treated with repetitive transcranial magnetic simulation for 7 consecutive days. Nonlinear electroencephalographic parameters were obtained from the rats at 7, 14, and 28 days post-stimulation. Results showed significantly lower mean correlation-dimension and Kolmogo-rov-entropy values for stimulated rats than for non-stimulated rats. At 28 days, the complexity and point-wise correlation dimensional values were lower in stimulated rats. Low-frequency repetitive transcranial magnetic simulation has suppressive effects on electrical activity in epileptic rats, thus explaining its effectiveness in treating epilepsy. PMID:25206567

Psycho-Social Aspects of Educating Epileptic Children: Roles for School Psychologists.

ERIC Educational Resources Information Center

Frank, Brenda B.

1985-01-01

Epileptic children may have physical and emotional needs which can interfere with learning and socialization. Current prevalence estimates, definitions, and classifications of epilepsy are surveyed. Factors affecting the epileptic child's school performance and specific learning problems are addressed. Specific roles are presented for school…

Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

PubMed

Bourdillon, Pierre; Apra, Caroline; Guénot, Marc; Duffau, Hugues

2017-12-01

To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Molecular and genetic insights into an infantile epileptic encephalopathy - CDKL5 disorder.

PubMed

Zhou, Ailing; Han, Song; Zhou, Zhaolan Joe

2017-02-01

The discovery that mutations in cyclin-dependent kinase-like 5 ( CDKL5 ) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes.

Molecular and genetic insights into an infantile epileptic encephalopathy – CDKL5 disorder

PubMed Central

Zhou, Ailing; Han, Song

2017-01-01

Background The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. Methods A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. Results On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Conclusions Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes. PMID:28580010

Nonlinear times series analysis of epileptic human electroencephalogram (EEG)

NASA Astrophysics Data System (ADS)

Li, Dingzhou

The problem of seizure anticipation in patients with epilepsy has attracted significant attention in the past few years. In this paper we discuss two approaches, using methods of nonlinear time series analysis applied to scalp electrode recordings, which is able to distinguish between epochs temporally distant from and just prior to, the onset of a seizure in patients with temporal lobe epilepsy. First we describe a method involving a comparison of recordings taken from electrodes adjacent to and remote from the site of the seizure focus. In particular, we define a nonlinear quantity which we call marginal predictability. This quantity is computed using data from remote and from adjacent electrodes. We find that the difference between the marginal predictabilities computed for the remote and adjacent electrodes decreases several tens of minutes prior to seizure onset, compared to its value interictally. We also show that these difl'crcnc es of marginal predictability intervals are independent of the behavior state of the patient. Next we examine the please coherence between different electrodes both in the long-range and the short-range. When time is distant from seizure onsets ("interictally"), epileptic patients have lower long-range phase coherence in the delta (1-4Hz) and beta (18-30Hz) frequency band compared to nonepileptic subjects. When seizures approach (''preictally"), we observe an increase in phase coherence in the beta band. However, interictally there is no difference in short-range phase coherence between this cohort of patients and non-epileptic subjects. Preictally short-range phase coherence also increases in the alpha (10-13Hz) and the beta band. Next we apply the quantity marginal predictability on the phase difference time series. Such marginal predictabilities are lower in the patients than in the non-epileptic subjects. However, when seizure approaches, the former moves asymptotically towards the latter.

Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino Glaxo Rijswijk rats.

PubMed

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.

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation.

PubMed

Cota, Vinícius Rosa; Drabowski, Bruna Marcela Bacellar; de Oliveira, Jasiara Carla; Moraes, Márcio Flávio Dutra

2016-06-01

Many patients with epilepsy do not obtain proper control of their seizures through conventional treatment. We review aspects of the pathophysiology underlying epileptic phenomena, with a special interest in the role of the amygdala, stressing the importance of hypersynchronism in both ictogenesis and epileptogenesis. We then review experimental studies on electrical stimulation of mesiotemporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy. Regular high-frequency stimulation (HFS) commonly has anticonvulsant effects and sparse antiepileptogenic properties. On the other hand, HFS is related to acute and long-term increases in excitability related to direct neuronal activation, long-term potentiation, and kindling, raising concerns regarding its safety and jeopardizing in-depth understanding of its mechanisms. In turn, the safer regular low-frequency stimulation (LFS) has a robust antiepileptogenic effect, but its pro- or anticonvulsant effect seems to vary at random among studies. As an alternative, studies by our group on the development and investigation of temporally unstructured electrical stimulation applied to the amygdala have shown that nonperiodic stimulation (NPS), which is a nonstandard form of LFS, is capable of suppressing both acute and chronic spontaneous seizures. We hypothesize two noncompetitive mechanisms for the therapeutic role of amygdala in NPS, 1) a direct desynchronization of epileptic circuitry in the forebrain and brainstem and 2) an indirect desynchronization/inhibition through nucleus accumbens activation. We conclude by reintroducing the idea that hypersynchronism, rather than hyperexcitability, may be the key for epileptic phenomena and epilepsy treatment. © 2016 Wiley Periodicals, Inc.

[Subacute encephalopathy with epileptic seizures in an alcoholic patient].

PubMed

Kozian, R; Otto, F G

2000-09-01

We introduce a case of a 66 year-old male with chronic alcoholism who suffered from confusion, Wernicke-aphasia and epileptic seizures. Several EEG revealed periodic lateralized epileptiform discharges. The patient's case resembles the symptoms of a subacute encephalopathy with epileptic seizures which can occur in alcoholics.

Attribution and Stereotype Explanations of Non-Visible Handicap Discrimination.

ERIC Educational Resources Information Center

Farrow, Dana

A male epileptic, male nonepileptic, female epileptic, or female nonepileptic job candidate was evaluated for either an auto sales or receptionist job by 112 university students in personnel or behavioral science courses. The female epileptic and the male nonepileptic candidates had significantly higher probabilities of being hired than the other…

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

PubMed Central

2012-01-01

Abstact Background 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. Methods 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. Results 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. Conclusions 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. PMID:22364254

Transplantation of bone marrow mononuclear cells modulates hippocampal expression of growth factors in chronically epileptic animals.

PubMed

Zanirati, Gabriele; Azevedo, Pamella Nunes; Marinowic, Daniel Rodrigo; Rodrigues, Felipe; de Oliveira Dias, Ana Christina; Venturin, Gianina Teribele; Greggio, Samuel; Simão, Fabrício; DaCosta, Jaderson Costa

2015-05-01

In previous studies, transplantation of bone marrow mononuclear cells (BMMCs) in epileptic animals has been found to be neuroprotective. However, the mechanism by which the BMMCs act remains unclear. We hypothesize that BMMCs may provide neuroprotection to the epileptic brain through trophic support. To test our hypothesis, we studied the temporal expression of neurotrophins after BMMC transplantation in the epileptic rat hippocampus. Chronically epileptic rats were intravenously transplanted with 1 × 10(7) BMMCs isolated from GFP transgenic mice. Expression levels of BDNF, GDNF, NGF, VEGF, and TGF-β1, and their receptors, were evaluated by ELISA and/or qRT-PCR analysis. Our data revealed increased protein expression of BDNF, GDNF, NGF, and VEGF and reduced levels of TGF-β1 in the hippocampus of transplanted epileptic animals. Additionally, an increase in the mRNA expression of BDNF, GDNF, and VEGF, a reduction in TGF-β1, and a decrease in mRNA levels of the TrkA and TGFR-β1 receptors were also observed. The gain provided by transplanted BMMCs in the epileptic brain may be related to the ability of these cells in modulating the network of neurotrophins and angiogenic signals. © 2015 John Wiley & Sons Ltd.

Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

PubMed

Radaelli, Graciane; de Souza Santos, Francisco; Borelli, Wyllians Vendramini; Pisani, Leonardo; Nunes, Magda Lahorgue; Scorza, Fulvio Alexandre; da Costa, Jaderson Costa

2018-06-12

Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe disease, but well-reported data are lacking to clarify EIEE-related causes of death. Copyright © 2018 Elsevier Inc. All rights reserved.

A role for the preoptic sleep-promoting system in absence epilepsy.

PubMed

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.

Ordinal patterns in epileptic brains: Analysis of intracranial EEG and simultaneous EEG-fMRI

NASA Astrophysics Data System (ADS)

Rummel, C.; Abela, E.; Hauf, M.; Wiest, R.; Schindler, K.

2013-06-01

Epileptic seizures are associated with high behavioral stereotypy of the patients. In the EEG of epilepsy patients characteristic signal patterns can be found during and between seizures. Here we use ordinal patterns to analyze EEGs of epilepsy patients and quantify the degree of signal determinism. Besides relative signal redundancy and the fraction of forbidden patterns we introduce the fraction of under-represented patterns as a new measure. Using the logistic map, parameter scans are performed to explore the sensitivity of the measures to signal determinism. Thereafter, application is made to two types of EEGs recorded in two epilepsy patients. Intracranial EEG shows pronounced determinism peaks during seizures. Finally, we demonstrate that ordinal patterns may be useful for improving analysis of non-invasive simultaneous EEG-fMRI.

Characterization of dynamical systems under noise using recurrence networks: Application to simulated and EEG data

NASA Astrophysics Data System (ADS)

Puthanmadam Subramaniyam, Narayan; Hyttinen, Jari

2014-10-01

In this letter, we study the influence of observational noise on recurrence network (RN) measures, the global clustering coefficient (C) and average path length (L) using the Rössler system and propose the application of RN measures to analyze the structural properties of electroencephalographic (EEG) data. We find that for an appropriate recurrence rate (RR>0.02) the influence of noise on C can be minimized while L is independent of RR for increasing levels of noise. Indications of structural complexity were found for healthy EEG, but to a lesser extent than epileptic EEG. Furthermore, C performed better than L in case of epileptic EEG. Our results show that RN measures can provide insights into the structural properties of EEG in normal and pathological states.

Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

ERIC Educational Resources Information Center

Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

2011-01-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

[Epilepsy from a metaphysical perspective: an interpretation of the biblical story of the epileptic boy and Raphael's Transfiguration].

PubMed

Janz, D

1994-01-01

Raphael's last painting reveals, in the upper half of the picture, Christ's transfiguration on Mount Tabor and, in the lower half, the young boy's epileptic seizure at the foot of the mountain in the presence of the other disciples. Raphael depicts both events, which are told in succession in the Gospels, as if they took place at the same time. By synchronizing both scenes, Raphael demonstrated a significant correspondence between Christ and the epileptic boy which reveals the epileptic seizure as a symbolic representation of a transcendental event. This metaphysical aspect of epilepsy depicted by Raphael can also be found in the corresponding biblical passages. In the Gospels, the metamorphosis caused by the epileptic seizure is used as a simile for Christ's transfiguration through suffering, death and resurrection.

Manganese intoxication: the cause of an inexplicable epileptic syndrome in a 3 year old child.

PubMed

Herrero Hernandez, Elena; Discalzi, Gianluigi; Dassi, Patrizia; Jarre, Laura; Pira, Enrico

2003-08-01

Excess manganese (Mn) can cause several neurotoxic effects, however only a few studies have reported epileptic syndromes related to manganese intoxication. We describe an epileptic syndrome due to manganese intoxication in a 3 year old male child. His blood manganese was elevated, but no other abnormal values or toxic substances were found in blood or urine. The electroencephalogram (EEG) showed a picture of progressive encephalopathy, while brain magnetic resonance was normal. The patient's conditions rapidly worsened to epileptic status despite the use of antiepileptic drugs. Chelating treatment with CaNa(2)EDTA was initiated to remove excess manganese and promptly succeeded in reverting epileptic symptoms. Concurrently, manganese blood levels and electroencephalogram progressively normalized. Thereafter it has been possible to discontinue antiepileptic treatment, and the patient remains in excellent conditions without any treatment.

Effect of epileptic seizures on the cerebrospinal fluid--A systematic retrospective analysis.

PubMed

Tumani, Hayrettin; Jobs, Catherine; Brettschneider, Johannes; Hoppner, Anselm C; Kerling, Frank; Fauser, Susanne

2015-08-01

Analyses of the cerebrospinal fluid (CSF) are obligatory when epileptic seizures manifest for the first time in order to exclude life-threatening causes or treatable diseases such as acute infections or autoimmune encephalitis. However, there are only few systematic investigations on the effect of seizures themselves on CSF parameters and the significance of these parameters in differential diagnosis. CSF samples of 309 patients with epileptic and 10 with psychogenic seizures were retrospectively analyzed. CSF samples were collected between 1999 and 2008. Cell counts, the albumin quotient, lactate and Tau-protein levels were determined. Findings were correlated with seizure types, seizure etiology (symptomatic, cryptogenic, occasional seizure), and seizure duration. Pathological findings were only observed in patients with epileptic but not with psychogenic seizures. The lactate concentration was elevated in 14%, the albumin quotient in 34%, and the Tau protein level in 36% of CSF samples. Cell counts were only slightly elevated in 6% of patients. Different seizure types influenced all parameters except for the cell count: In status epilepticus highest, in simple partial seizures lowest values were seen. Symptomatic partial and generalized epileptic seizures had significantly higher Tau-protein levels than cryptogenic partial seizures. In patients with repetitive and occasional epileptic seizures, higher Tau-protein levels were seen than in those with psychogenic seizures. Duration of epileptic seizures was positively correlated with the albumin quotient, lactate and Tau-protein levels. High variability of investigated CSF parameters within each subgroup rendered a clear separation between epileptic and psychogenic seizures impossible. Elevated cell counts are infrequently observed in patients with epileptic seizures and should therefore not uncritically be interpreted as a postictal phenomenon. However, blood-CSF barrier disruption, increased glucose metabolism and elevation of neuronal damage markers are observed in considerable percentages of patients and depend on many factors such as etiology, seizure type and duration. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Age-Dependency of Location of Epileptic Foci in "Continuous Spike-and-Waves during Sleep": A Parallel to the Posterior-Anterior Trajectory of Slow Wave Activity.

PubMed

Bölsterli Heinzle, Bigna Katrin; Bast, Thomas; Critelli, Hanne; Huber, Reto; Schmitt, Bernhard

2017-02-01

Epileptic encephalopathy with continuous spike-and-waves during sleep (CSWS) occurs during childhood and is characterized by an activation of spike wave complexes during slow wave sleep. The location of epileptic foci is variable, as is etiology. A relationship between the epileptic focus and age has been shown in various focal epilepsies following a posterior-anterior trajectory, and a link to brain maturation has been proposed. We hypothesize that in CSWS, maximal spike wave activity, corresponding to the epileptic focus, is related to age and shows a posterior-anterior evolution. In a retrospective cross-sectional study on CSWS (22 EEGs of 22 patients aged 3.1–13.5 years), the location of the epileptic focus is related to age and follows a posterior-anterior course. Younger patients are more likely to have posterior foci than older ones. We propose that the posterior-anterior trajectory of maximal spike waves in CSWS might reflect maturational changes of maximal expression of sleep slow waves, which follow a comparable course. Epileptic spike waves, that is, “hyper-synchronized slow waves” may occur at the place where the highest and therefore most synchronized slow waves meet brain tissue with an increased susceptibility to synchronization. Georg Thieme Verlag KG Stuttgart · New York.

The association between seizures and deposition of collagen in the brain in porcine Taenia solium neurocysticercosis.

PubMed

Christensen, Nina M; Trevisan, Chiara; Leifsson, Páll S; Johansen, Maria V

2016-09-15

Neurocysticercosis caused by infection with Taenia solium is a significant cause of epilepsy and seizures in humans. The aim of this study was to assess the association between seizures and the deposition of collagen in brain tissue in pigs with T. solium neurocysticercosis. In total 78 brain tissue sections from seven pigs were examined histopathologically i.e. two pigs with epileptic seizures and T. solium cysts, four pigs without seizures but with cysts, and one non-infected control pig. Pigs with epileptic seizures had a larger amount of collagen in their brain tissue, showing as large fibrotic scars and moderate amount of collagen deposited around cysts, compared to pigs without seizures and the negative control pig. Our results indicate that collagen is likely to play a considerable part in the pathogenesis of seizures in T. solium neurocysticercosis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Etomidate accurately localizes the epileptic area in patients with temporal lobe epilepsy.

PubMed

Pastor, Jesús; Wix, Rybel; Meilán, María Luisa; Martínez-Chacón, José Luís; de Dios, Eva; Domínguez-Gadea, Luis; Herrera-Peco, Iván; Sola, Rafael G

2010-04-01

A variety of drugs have been used to activate and identify the epileptogenic area in patients during presurgical evaluation. We have evaluated the safety and usefulness of etomidate in identifying the epileptic zone by measuring bioelectrical brain activity and cerebral blood flow (CBF). We studied 13 men and 9 women under presurgical evaluation for temporal lobe epilepsy. We applied etomidate (0.1 mg/kg) while patients were monitored by video-electroencephalography (VEEG) with foramen ovale electrodes. In a subset of 15 patients, we also measured CBF with single photon emission computed tomography (SPECT). (1) Etomidate induced seizures in 2 of 22 patients. (2) The main side-effects observed were myoclonus (14 of 20) and moderate pain (3 of 20). (3) No changes in capillary oxygen saturation, respiration, or heart rate were observed. (4) Irritative activity specifically increased in the temporal mesial and lateral areas. No spikes were observed in other areas, aside from those observed under baseline conditions. (5) Irritative activity induced by etomidate correctly lateralized the ictal onset zone in 19 of 20 patients. In addition, the two etomidate-induced seizures appeared in the same regions as spontaneous ones. (6) The kinetics of pharmacologically induced activity was higher in the region of the ictal-onset zone. (7) Etomidate increased the CBF in the basal ganglia and especially in the posterior hippocampus of the temporal mesial region contralateral to the ictal-onset zone. Etomidate activation is a safe, specific, and quick test that can be used to identify the epileptic region in patients evaluated as candidates for temporal lobe epilepsy surgery.

Electroencephalography and phenytoin toxicity in mentally retarded epileptic patients.

PubMed Central

Iivanainen, M; Viukari, M; Seppäläinen, A M; Helle, E P

1978-01-01

There were significantly more diffuse and focal electroencephalographic abnormalities in 127 mentally retarded epileptic patients treated with phenytoin than in 68 epileptics without phenytoin. Phenytoin intoxication made the difference still more pronounced. Monitoring drug levels and electroencephalograms appears to be the method of choice for ensuring safe and effective medication in intractable epilepsy. PMID:632825

Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom.

PubMed

Tong, Man-Li; Liu, Li-Li; Zeng, Yan-Li; Zhang, Hui-Lin; Liu, Gui-Li; Zheng, Wei-Hong; Dong, Jie; Wu, Jing-Yi; Su, Yuan-Hui; Lin, Li-Rong; Yang, Tian-Ci

2013-04-01

A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS. Copyright © 2013 Elsevier Inc. All rights reserved.

[The role of ambulatory electroencephalogram monitoring: experience and results in 264 records].

PubMed

González de la Aleja, J; Saiz Díaz, R A; Martín García, H; Juntas, R; Pérez-Martínez, D; de la Peña, P

2008-11-01

Ambulatory electroencephalogram (EEG) monitoring allows for long-term, mobile electroencephalographic recordings of patients. This study aims to describe and analyze the results obtained with ambulatory EEG in our clinical practice. We have analyzed the results of 264 ambulatory EEG records, grouped according to the reason for the request: a) group 1: diagnostic evaluation of episodes of epileptic nature; b) group 2: diagnostic evaluation of paroxysmal episodes, and c) group 3: evaluation of the risk of relapse during anti-seizure treatment withdrawal in certain epileptic patients. a) Group 1 (n=137): normal results were found in 54 records (39.4%). There was generalized epileptic activity in 20 (14.6%) of them (5 with ictal activity) and focal epileptic activity was detected in 57 cases (42%) (8 with ictal activity). No EEG diagnosis could be reached in 6 (4%) recordings due to the presence of artefacts; b) group 2 (n=99): in 47 records (47.5 %), there were no episodes and the Holter-EEG was normal. There was a clinically documented episode without anomalies during Holter-EEG registration in 14 cases (14.2%). In 29 records (29.3%), focal epileptic activity was recorded (ictal 4) and generalized epileptic activity (ictal in 1) was recorded in 4 patients (4%). No EEG diagnosis could be reached in 5 cases (5%), and c) group 3 (n=28): the study was normal in 15 cases (53.6%) and showed focal interictal epileptic activity in 8 (28.6 %) and generalized interictal epileptic activity in 5 of them (17.8%). We believe that the ambulatory EEG recordings in correctly selected cases can provide important additional information regarding global assessment of patients with epilepsy.

Clinical review of genetic epileptic encephalopathies

PubMed Central

Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

2012-01-01

Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633

Autonomic headache with autonomic seizures: a case report.

PubMed

Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet

2006-10-01

The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

Epilepsy is a possible feature in Williams-Beuren syndrome patients harboring typical deletions of the 7q11.23 critical region.

PubMed

Nicita, Francesco; Garone, Giacomo; Spalice, Alberto; Savasta, Salvatore; Striano, Pasquale; Pantaleoni, Chiara; Spartà, Maria Valentina; Kluger, Gerhard; Capovilla, Giuseppe; Pruna, Dario; Freri, Elena; D'Arrigo, Stefano; Verrotti, Alberto

2016-01-01

Seizures are rarely reported in Williams-Beuren syndrome (WBS)--a contiguous-gene-deletion disorder caused by a 7q11.23 heterozygous deletion of 1.5-1.8 Mb--and no previous study evaluated electro-clinical features of epilepsy in this syndrome. Furthermore, it has been hypothesized that atypical deletion (e.g., larger than 1.8 Mb) may be responsible for a more pronounced neurological phenotypes, especially including seizures. Our objectives are to describe the electro-clinical features in WBS and to correlate the epileptic phenotype with deletion of the 7q11.23 critical region. We evaluate the electro-clinical features in one case of distal 7q11.23 deletion syndrome and in eight epileptic WBS (eWBS) patients. Additionally, we compare the deletion size-and deleted genes-of four epileptic WBS (eWBS) with that of four non-epileptic WBS (neWBS) patients. Infantile spasms, focal (e.g., motor and dyscognitive with autonomic features) and generalized (e.g., tonic-clonic, tonic, clonic, myoclonic) seizures were encountered. Drug-resistance was observed in one patient. Neuroimaging discovered one case of focal cortical dysplasia, one case of fronto-temporal cortical atrophy and one case of periventricular nodular heterotopia. Comparison of deletion size between eWBS and neWBS patients did not reveal candidate genes potentially underlying epilepsy. This is the largest series describing electro-clinical features of epilepsy in WBS. In WBS, epilepsy should be considered both in case of typical and atypical deletions, which do not involve HIP1, YWHAG or MAGI2. © 2015 Wiley Periodicals, Inc.

Video/EEG aspects of early-infantile epileptic encephalopathy with suppression-bursts (Ohtahara syndrome).

PubMed

Fusco, L; Pachatz, C; Di Capua, M; Vigevano, F

2001-11-01

Early-infantile epileptic encephalopathy (EIEE) with suppression-bursts is a severe neonatal epileptic encephalopathy. The etiology is multiple, with cerebral malformations as the more frequent. We review the clinical and video/EEG aspects of eight infants with EIEE. These infants, aged between 4 and 70 days at the time of video/EEG recordings, were studied in relation to their clinical and video/EEG characteristics, evolution, persistence of suppression-burst pattern and etiology. Seven of the eight infants showed an ictal clinical sign correlated to the burst of the suppression-burst pattern, four of whom died within 11 months of age. The other three are alive. One, now aged 4 years, underwent surgery for hemimegalencephaly and is seizure-free, with good neurological outcome. One, now aged 9 months, was pyridoxine-dependent and she is seizure-free, and with normal neurological evolution under pyridoxine therapy. One, now aged 3 years and 9 months, is seizure-free, but with severe neurological and cognitive impairment. The only child who did not show a clinical ictal correlation of burst is also alive, now aged 3 years and 9 months, with drug-resistant epilepsy, and severe neurological and cognitive deficits. With regard to the etiology, three showed structural abnormalities, two more showed some signs of prenatal origin of neurological disease, and three had metabolic etiology. Our study confirms that EIEE is a severe age-dependent early epileptic encephalopathy. The etiology is mostly malformative. The prognosis is poor regarding motor and cognitive development, seizures, as well as life expectancies. The presence of an ictal burst of the suppression-burst pattern usually correlates with a negative outcome.

The contribution of raised intraneuronal chloride to epileptic network activity.

PubMed

Alfonsa, Hannah; Merricks, Edward M; Codadu, Neela K; Cunningham, Mark O; Deisseroth, Karl; Racca, Claudia; Trevelyan, Andrew J

2015-05-20

Altered inhibitory function is an important facet of epileptic pathology. A key concept is that GABAergic activity can become excitatory if intraneuronal chloride rises. However, it has proved difficult to separate the role of raised chloride from other contributory factors in complex network phenomena, such as epileptic pathology. Therefore, we asked what patterns of activity are associated with chloride dysregulation by making novel use of Halorhodopsin to load clusters of mouse pyramidal cells artificially with Cl(-). Brief (1-10 s) activation of Halorhodopsin caused substantial positive shifts in the GABAergic reversal potential that were proportional to the charge transfer during the illumination and in adult neocortical pyramidal neurons decayed with a time constant of τ = 8.0 ± 2.8s. At the network level, these positive shifts in EGABA produced a transient rise in network excitability, with many distinctive features of epileptic foci, including high-frequency oscillations with evidence of out-of-phase firing (Ibarz et al., 2010). We show how such firing patterns can arise from quite small shifts in the mean intracellular Cl(-) level, within heterogeneous neuronal populations. Notably, however, chloride loading by itself did not trigger full ictal events, even with additional electrical stimulation to the underlying white matter. In contrast, when performed in combination with low, subepileptic levels of 4-aminopyridine, Halorhodopsin activation rapidly induced full ictal activity. These results suggest that chloride loading has at most an adjunctive role in ictogenesis. Our simulations also show how chloride loading can affect the jitter of action potential timing associated with imminent recruitment to an ictal event (Netoff and Schiff, 2002). Copyright © 2015 Alfonsa et al.

Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

PubMed

Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

2015-07-01

Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

Retrospective epidemiological study of canine epilepsy in Japan using the International Veterinary Epilepsy Task Force classification 2015 (2003-2013): etiological distribution, risk factors, survival time, and lifespan.

PubMed

Hamamoto, Yuji; Hasegawa, Daisuke; Mizoguchi, Shunta; Yu, Yoshihiko; Wada, Masae; Kuwabara, Takayuki; Fujiwara-Igarashi, Aki; Fujita, Michio

2016-11-09

Epilepsy is the most common neurological disease in veterinary practice. However, contrary to human medicine, epilepsy classification in veterinary medicine had not been clearly defined until recently. A number of reports on canine epilepsy have been published, reflecting in part updated proposals from the human epilepsy organization, the International League Against Epilepsy. In 2015, the International Veterinary Epilepsy Task Force (IVETF) published a consensus report on the classification and definition of canine epilepsy. The purpose of this retrospective study was to investigate the etiological distribution, survival time of dogs with idiopathic epilepsy (IdE) and structural epilepsy (StE), and risk factors for survival time, according to the recently published IVETF classification. We investigated canine cases with epilepsy that were referred to our teaching hospital in Japan during the past 10 years, and which encompassed a different breed population from Western countries. A total of 358 dogs with epilepsy satisfied our etiological study criteria. Of these, 172 dogs (48 %) were classified as IdE and 76 dogs (21 %) as StE. Of these dogs, 100 dogs (consisting of 65 with IdE and 35 with StE) were included in our survival study. Median survival time from the initial epileptic seizure in dogs with IdE and StE was 10.4 and 4.5 years, respectively. Median lifespan of dogs with IdE and StE was 13.5 and 10.9 years, respectively. Multivariable analysis demonstrated that risk factors for survival time in IdE were high seizure frequency (≥0.3 seizures/month) and focal epileptic seizures. Focal epileptic seizures were identified as a risk factor for survival time in IdE. Clinicians should carefully differentiate seizure type as it is difficult to identify focal epileptic seizures. With good seizure control, dogs with IdE can survive for nearly the same lifespan as the general dog population. Our results using the IVETF classification are similar to previous studies, although some features were noted in our Japanese canine population (which was composed of mainly small-breed dogs), including a longer lifespan in dogs with epilepsy and a larger percentage of meningoencephalomyelitis of unknown origin in dogs with StE.

Transcranial Direct Current Stimulation in Epilepsy.

PubMed

San-Juan, Daniel; Morales-Quezada, León; Orozco Garduño, Adolfo Josué; Alonso-Vanegas, Mario; González-Aragón, Maricarmen Fernández; Espinoza López, Dulce Anabel; Vázquez Gregorio, Rafael; Anschel, David J; Fregni, Felipe

2015-01-01

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation therapy in epilepsy with conflicting results in terms of efficacy and safety. Review the literature about the efficacy and safety of tDCS in epilepsy in humans and animals. We searched studies in PubMed, MedLine, Scopus, Web of Science and Google Scholar (January 1969 to October 2013) using the keywords 'transcranial direct current stimulation' or 'tDCS' or 'brain polarization' or 'galvanic stimulation' and 'epilepsy' in animals and humans. Original articles that reported tDCS safety and efficacy in epileptic animals or humans were included. Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines and Jadad Scale. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. We analyzed 9 articles with different methodologies (3 animals/6 humans) with a total of 174 stimulated individuals; 109 animals and 65 humans. In vivo and in vitro animal studies showed that direct current stimulation can successfully induce suppression of epileptiform activity without neurological injury and 4/6 (67%) clinical studies showed an effective decrease in epileptic seizures and 5/6 (83%) reduction of inter-ictal epileptiform activity. All patients tolerated tDCS well. tDCS trials have demonstrated preliminary safety and efficacy in animals and patients with epilepsy. Further larger studies are needed to define the best stimulation protocols and long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

An 81.6 μW FastICA processor for epileptic seizure detection.

PubMed

Yang, Chia-Hsiang; Shih, Yi-Hsin; Chiueh, Herming

2015-02-01

To improve the performance of epileptic seizure detection, independent component analysis (ICA) is applied to multi-channel signals to separate artifacts and signals of interest. FastICA is an efficient algorithm to compute ICA. To reduce the energy dissipation, eigenvalue decomposition (EVD) is utilized in the preprocessing stage to reduce the convergence time of iterative calculation of ICA components. EVD is computed efficiently through an array structure of processing elements running in parallel. Area-efficient EVD architecture is realized by leveraging the approximate Jacobi algorithm, leading to a 77.2% area reduction. By choosing proper memory element and reduced wordlength, the power and area of storage memory are reduced by 95.6% and 51.7%, respectively. The chip area is minimized through fixed-point implementation and architectural transformations. Given a latency constraint of 0.1 s, an 86.5% area reduction is achieved compared to the direct-mapped architecture. Fabricated in 90 nm CMOS, the core area of the chip is 0.40 mm(2). The FastICA processor, part of an integrated epileptic control SoC, dissipates 81.6 μW at 0.32 V. The computation delay of a frame of 256 samples for 8 channels is 84.2 ms. Compared to prior work, 0.5% power dissipation, 26.7% silicon area, and 3.4 × computation speedup are achieved. The performance of the chip was verified by human dataset.

How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?

PubMed

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.

Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex.

PubMed

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.

Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex

PubMed Central

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

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

PubMed

Matos, Gabriela; Ribeiro, Daniel A; Alvarenga, Tathiana A; Hirotsu, Camila; Scorza, Fulvio A; Le Sueur-Maluf, Luciana; Noguti, Juliana; Cavalheiro, Esper A; Tufik, Sergio; Andersen, Monica L

2012-05-02

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

PubMed

Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

2016-03-01

Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Correlates of Age-Dependent Seizures in an Inherited Neonatal-Infantile Epilepsy

ERIC Educational Resources Information Center

Liao, Yunxiang; Deprez, Liesbet; Maljevic, Snezana; Pitsch, Julika; Claes, Lieve; Hristova, Dimitrina; Jordanova, Albena; Ala-Mello, Sirpa; Bellan-Koch, Astrid; Blazevic, Dragica; Schubert, Simone; Thomas, Evan A.; Petrou, Steven; Becker, Albert J.; De Jonghe, Peter; Lerche, Holger

2010-01-01

Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial…

[Ivermectin as an adjunct in the treatment of refractory epilepsy].

PubMed

Diazgranados-Sanchez, J A; Mejia-Fernandez, J L; Chan-Guevara, L S; Valencia-Artunduaga, M H; Costa, J L

2017-10-01

Ivermectin, a 22'23 dihydro derivative of avermectins beta-1a, is a highly effective veterinary and human anti parasitic, used to treat endoparasites of difficult control such as filariasis and onchocerciasis, with a median plasma life of at least of 16 hours. The recommended therapeutic doses range from 0.05 to 0.40 mg/kg, without undesirable effects or risk to human life. It went from being a great success in animal health to its application in humans, where it has had great impact. Studies in basic sciences have shown that ivermectin has anticonvulsive effects in different epileptic animal models, where five different mechanisms of action have been described. Descriptive, prospective observational study, performed between 2013 and 2015, with 32 refractory epileptic patients, who received ivermectin as an a dose of adjunctive treatment of 10 mg/day three or seven times a week, controlled every three months, followed by 12-24 months, without withdrawal of anticonvulsant medications that they received previously. Progressively, patients entered into crisis control, at the end of the programmed follow-up period, the total percentage of crisis reduction was 97%, of which 57% did not return to crisis from the beginning of treatment, all patients being free of crisis according to International League Against Epilepsy criteria. Ivermectin has been useful as an adjuvant, achieving a significant decrease in seizures in this group of drug resistant patients.

Recurrent epileptic Wernicke aphasia.

PubMed

Sahaya, Kinshuk; Dhand, Upinder K; Goyal, Munish K; Soni, Chetan R; Sahota, Pradeep K

2010-04-15

We report a patient with recurrent epileptic Wernicke aphasia who prior to this presentation, had been misdiagnosed as transient ischemic attacks for several years. This case report emphasizes the consideration of epileptic nature of aphasia when a clear alternate etiology is unavailable, even when EEG fails to show a clear ictal pattern. We also present a brief discussion of previously reported ictal aphasias. Copyright 2010 Elsevier B.V. All rights reserved.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

NASA Astrophysics Data System (ADS)

Pothof, F.; Bonini, L.; Lanzilotto, M.; Livi, A.; Fogassi, L.; Orban, G. A.; Paul, O.; Ruther, P.

2016-08-01

Objective. Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Approach. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Main results. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. Significance. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites.

PubMed

Pothof, F; Bonini, L; Lanzilotto, M; Livi, A; Fogassi, L; Orban, G A; Paul, O; Ruther, P

2016-08-01

Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

A novel mutation in STXBP1 gene in a child with epileptic encephalopathy and an atypical electroclinical pattern.

PubMed

Romaniello, Romina; Zucca, Claudio; Tenderini, Erika; Arrigoni, Filippo; Ragona, Francesca; Zorzi, Giovanna; Bassi, Maria Teresa; Borgatti, Renato

2014-02-01

Mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies. A 3-year-old boy affected by epileptic encephalopathy started at 8 months of age is described. Focal epilepsy was characterized by drug resistance seizures with multifocal interictal and ictal electroencephalographic (EEG) features and variable EEG focus. Direct sequencing of the STXBP1 gene showed a novel de novo mutation (c.751G>A), leading to a p.Ala251Thr substitution. Based on reported data, treatment with vigabatrin was attempted and patient became immediately seizure free for 4 months. The present case further expands the clinical spectrum of "STXBP1-related encephalopathy" suggesting molecular analysis of STXBP1 in early onset epileptic encephalopathies of unknown etiology (with onset within the first year of life). In addition, the case provides valuable suggestions on seizures treatment in STXBP1 mutated subjects.

Epileptic Seizure Prediction Using a New Similarity Index for Chaotic Signals

NASA Astrophysics Data System (ADS)

Niknazar, Hamid; Nasrabadi, Ali Motie

Epileptic seizures are generated by abnormal activity of neurons. The prediction of epileptic seizures is an important issue in the field of neurology, since it may improve the quality of life of patients suffering from drug resistant epilepsy. In this study a new similarity index based on symbolic dynamic techniques which can be used for extracting behavior of chaotic time series is presented. Using Freiburg EEG dataset, it is found that the method is able to detect the behavioral changes of the neural activity prior to epileptic seizures, so it can be used for prediction of epileptic seizure. A sensitivity of 63.75% with 0.33 false positive rate (FPR) in all 21 patients and sensitivity of 96.66% with 0.33 FPR in eight patients were achieved using the proposed method. Moreover, the method was evaluated by applying on Logistic and Tent map with different parameters to demonstrate its robustness and ability in determining similarity between two time series with the same chaotic characterization.

Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics.

PubMed

Serletis, Demitre; Bardakjian, Berj L; Valiante, Taufik A; Carlen, Peter L

2012-10-01

Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/f(γ) noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders.

A Novel Dynamic Update Framework for Epileptic Seizure Prediction

PubMed Central

Wang, Minghui; Hong, Xiaojun; Han, Jie

2014-01-01

Epileptic seizure prediction is a difficult problem in clinical applications, and it has the potential to significantly improve the patients' daily lives whose seizures cannot be controlled by either drugs or surgery. However, most current studies of epileptic seizure prediction focus on high sensitivity and low false-positive rate only and lack the flexibility for a variety of epileptic seizures and patients' physical conditions. Therefore, a novel dynamic update framework for epileptic seizure prediction is proposed in this paper. In this framework, two basic sample pools are constructed and updated dynamically. Furthermore, the prediction model can be updated to be the most appropriate one for the prediction of seizures' arrival. Mahalanobis distance is introduced in this part to solve the problem of side information, measuring the distance between two data sets. In addition, a multichannel feature extraction method based on Hilbert-Huang transform and extreme learning machine is utilized to extract the features of a patient's preseizure state against the normal state. At last, a dynamic update epileptic seizure prediction system is built up. Simulations on Freiburg database show that the proposed system has a better performance than the one without update. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices. PMID:25050381

A novel dynamic update framework for epileptic seizure prediction.

PubMed

Han, Min; Ge, Sunan; Wang, Minghui; Hong, Xiaojun; Han, Jie

2014-01-01

Epileptic seizure prediction is a difficult problem in clinical applications, and it has the potential to significantly improve the patients' daily lives whose seizures cannot be controlled by either drugs or surgery. However, most current studies of epileptic seizure prediction focus on high sensitivity and low false-positive rate only and lack the flexibility for a variety of epileptic seizures and patients' physical conditions. Therefore, a novel dynamic update framework for epileptic seizure prediction is proposed in this paper. In this framework, two basic sample pools are constructed and updated dynamically. Furthermore, the prediction model can be updated to be the most appropriate one for the prediction of seizures' arrival. Mahalanobis distance is introduced in this part to solve the problem of side information, measuring the distance between two data sets. In addition, a multichannel feature extraction method based on Hilbert-Huang transform and extreme learning machine is utilized to extract the features of a patient's preseizure state against the normal state. At last, a dynamic update epileptic seizure prediction system is built up. Simulations on Freiburg database show that the proposed system has a better performance than the one without update. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices.

Effects of valproate on the carotid artery intima-media thickness in epileptics.

PubMed

Luo, Xinming; Zhang, Ming; Deng, Liying; Zhao, Jing

2015-01-01

The objective was to explore the effects of valproate (VPA) on the carotid artery intima-media thickness (CA-IMT) in epileptics. A total of 30 epileptic patients treated with VPA was included as disease group, while 33 healthy people who matched general basic demographic details were the control group. The IMTs of the left and right carotids of the both groups were measured, and the average CA-IMT was calculated. The IMT-related risk factors were acquired for the univariate and multivariate analysis. The bilateral carotid and average CA-IMTs of the disease group were significantly higher than the control group (P < 0.001). The multivariant gradual regressive analysis screened out two CA-IMT-related factors, namely the disease duration and the drug administration duration were positively correlated with the average CA-IMT. The epileptic patients with disease course of more than 3 years had much higher average CA-IMT than that of the epileptics with ≤3 years disease (P < 0.001). The average CA-IMT of the patients with VPA-administration duration >1 year was also higher than that of the patients with VPA-administration duration <1 year, while the difference was not statistically significant (P = 0.196). The average CA-IMT of the epileptic patients treated with VPA was higher than that of healthy people.

[Association between autism spectrum disorder and epilepsy in children].

PubMed

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.

Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA.

PubMed

Löscher, W; Fassbender, C P; Gram, L; Gramer, M; Hörstermann, D; Zahner, B; Stefan, H

1993-03-01

The novel antiepileptic drug vigabatrin (Sabril) acts by inhibiting degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), increasing the GABA concentrations in the brain. Because the GABA degrading enzyme GABA aminotransferase (GABA-T) is also present in peripheral tissues, including blood platelets, measurement of plasma GABA levels might be a useful indication of the pharmacological response to vigabatrin during therapeutic monitoring. However, because of the very low concentrations of GABA in plasma, the few methods available for plasma GABA analysis are time-consuming, difficult to perform and/or not selective enough because of potential interference with other plasma constituents. In the present study, a rapid, selective and sensitive amino acid analysis HPLC method has been developed for plasma GABA determination with fluorescence detection, using o-phthaldialdehyde as a precolumn derivatizing agent. By employing a 3 microns particle size reversed-phase column and a multi-step gradient system of two solvents, the very low endogenous concentration of GABA in human plasma could be reproducibly quantitated without interference of other endogenous compounds. Incubation of human plasma samples with GABA degrading enzyme(s) resulted in an almost total loss of the GABA peak, thus demonstrating the specificity of the method for GABA analysis. In addition to GABA and other endogenous amino acids, the HPLC method could be used to quantitate plasma levels of vigabatrin. Thus, this improved HPLC amino acid assay might be used to examine whether concomitant monitoring of plasma GABA and vigabatrin is useful for clinical purposes. This was examined in 20 epileptic patients undergoing chronic treatment with vigabatrin. The average plasma GABA level of these 20 patients did not differ significantly from non-epileptic controls. However, when epileptic patients were subdivided according to their clinical response to vigabatrin, vigabatrin responders had significantly higher GABA levels than nonresponders or controls. In contrast to the difference in plasma GABA, vigabatrin responders and nonresponders did not differ in dose or plasma level of vigabatrin. These data may indicate that determination of plasma GABA is a valuable non-invasive method for therapeutic monitoring in patients on medication with vigabatrin.

Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

PubMed Central

Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

2014-01-01

Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed. PMID:25105891

Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy: ameliorative effects of Withania somnifera and Withanolide A.

PubMed

Soman, Smijin; Korah, P K; Jayanarayanan, S; Mathew, Jobin; Paulose, C S

2012-09-01

In the present study we investigate the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring spatial memory deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. We demonstrate significant cellular loss in hippocampus of epileptic rats, visualized through decreased TOPRO stained neurons. Impaired spatial memory was observed in epileptic rats after Radial arm maze test. Treatment with WS and WA has resulted in increased number of TOPRO stained neurons. Enhanced performance of epileptic rats treated with WS and WA was observed in Radial arm maze test. The antioxidant activity of WS and WA was studied using superoxide dismutase (SOD) and Catalase (CAT) assays in the hippocampus of experimental rats. The SOD activity and CAT activity decreased significantly in epileptic group, treatment with WS and WA significantly reversed the enzymatic activities to near control. Real time gene expression studies of SOD and GPx showed significant up-regulation in epileptic group compared to control. Treatment with WS and WA showed significant reversal to near control. Lipid peroxidation quantified using TBARS assay, significantly increased in epileptic rats. Treatment with WS and WA showed significant reversal to near control. NMDA receptor expression decreased in epileptic rats. The treatment with WS and WA resulted in physiological expression of NMDA receptors. This data suggests that oxidative stress effects membrane constitution resulting in decreased NMDA receptor density leading to impaired spatial memory. Treatment with WS and WA has ameliorated spatial memory deficits by enhancing antioxidant system and restoring altered NMDA receptor density.

Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine

PubMed Central

Poorrostami, Ameneh; Farokhi, Farah; Heidari, Reza

2014-01-01

Objective: Lamotrigine is an antiepileptic drug, widely used in the treatment of epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber officinale Roscoe (ginger) possesses antioxidant properties. In present research, the effect ofhydroalcoholic extract of ginger (HEG) on the liver of lamotrigine-treated epileptic rats was investigated Material and Methods: Forty-eight female Wistar rats were selected and allocated to 8 groups of 6 each. Group 1: Negative controls were treated with normal saline. Group 2: Positive controls were treated with lamotrigine (LTG) (10 mg/kg) daily by gavages for 4 consecutive weeks. Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol (PTZ) (40 mg/kg). Group 3: Epileptic group received normal saline (10 ml/kg). Group 4: Epileptic group was treated with LTG (10 mg/kg). Groups 5 and 6: Epileptic groups received HEG (50 and 100 mg/kg). Groups 7 and 8: Epileptic groups received LTG and HEG (50 and 100 mg/kg). At the end of 28 days, blood samples were drawn and their livers were processed for light microscopy. Results: The mean values of TG, CHOL, AST, and ALT activity significantly rose (p<0.01) in groups 2, 3, and 4, while in rats treated with HEG (groups 5, 6, 7, and 8), the levels of liver enzymes significantly decreased (p<0.05) compared with epileptic group treated with lamotrigine (group 4). Histopathological changes of liver samples were comparable with respective control. Conclusion: These results suggest that hydroalcoholic extract of ginger improves liver function in lamotrigine-induced hepatotoxicity. PMID:25068142

The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

PubMed

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 feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction of Acute Seizures in Epileptic Rodents a Suitable Approach?

PubMed

Löscher, Wolfgang

2017-07-01

Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs), so that more effective ASDs are urgently needed. For this purpose, it would be important to develop, validate, and implement new animal models of pharmacoresistant epilepsy into drug discovery. Several chronic animal models with difficult-to-treat SRS do exist; however, most of these models are not suited for drug screening, because drug testing on SRS necessitates laborious video-EEG seizure monitoring. More recently, it was proposed that, instead of monitoring SRS, chemical or electrical induction of acute seizures in epileptic rodents may be used as a surrogate for testing the efficacy of novel ASDs against refractory SRS. Indeed, several ASDs were shown to lose their efficacy on acute seizures, when such seizures were induced by pentylenetetrazole (PTZ) in epileptic rather than nonepileptic rats, whereas this was not observed when using the maximal electroshock seizure test. Subsequent studies confirmed the loss of anti-seizure efficacy of valproate against PTZ-induced seizures in epileptic mice, but several other ASDs were more potent against PTZ in epileptic than nonepileptic mice. This was also observed when using the 6-Hz model of partial seizures in epileptic mice, in which the potency of levetiracetam, in particular, was markedly increased compared to nonepileptic animals. Overall, these observations suggest that performing acute seizure tests in epileptic rodents provides valuable information on the pharmacological profile of ASDs, in particular those with mechanisms inherent to disease-induced brain alterations. However, it appears that further work is needed to define optimal approaches for acute seizure induction and generation of epileptic/drug refractory animals that would permit reliable screening of new ASDs with improved potential to provide seizure control in patients with pharmacoresistant epilepsy.

Dupuytren's contracture: emerging insight into a Viking disease.

PubMed

Nunn, Adam C; Schreuder, Fred B

2014-01-01

Dupuytren's disease is a fibroproliferative condition of the palm, with a predilection for men, which has affected Northern Europeans since the Viking conquests. Although strongly heritable, clear evidence exists for environmental factors that modify the underlying genetic risk, such as diabetes, heavy drinking, and smoking. Evidence also exists for epilepsy (probably due to treatment with certain anti-epileptic drugs), and Human Immunodeficiency Virus infection. Recent large studies have shown no relationship with manual labour or vibrating tools. Two theories have emerged regarding the pathogenic mechanism: the first attributes the aberrant healing process that characterises Dupuytren's to free radicals, generated as a result of microangiopathy, whereas the second cites a genetic tendency toward apoptosis-resistant myofibroblasts. Despite only one study demonstrating linkage, emerging data from genome-wide association studies highlight a series of single nucleotide polymorphisms near members of the Wnt signalling pathway, and transcriptional profiling studies have consistently identified certain components of the extracellular matrix.

Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.

PubMed

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.

Genetics of Severe Early Onset Epilepsies

ClinicalTrials.gov

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

Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: Expansion of the genotypic and phenotypic spectrum.

PubMed

Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim

2016-07-01

Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

GABAergic transmission facilitates ictogenesis and synchrony between CA3, hilus, and dentate gyrus in slices from epileptic rats

PubMed Central

Gafurov, Boris

2013-01-01

The impact of regional hippocampal interactions and GABAergic transmission on ictogenesis remain unclear. Cortico-hippocampal slices from pilocarpine-treated epileptic rats were compared with controls to investigate associations between seizurelike events (SLE), GABAergic transmission, and neuronal synchrony within and between cortico-hippocampal regions. Multielectrode array recordings revealed more prevalent hippocampal SLE in epileptic tissue when excitatory transmission was enhanced and GABAergic transmission was intact [removal of Mg2+ (0Mg)] than when GABAergic transmission was blocked [removal of Mg2+ + bicuculline methiodide (0Mg+BMI)]. When activity within individual regions was analyzed, spectral and temporal slow oscillation/SLE correlations and cross-correlations were highest within the hilus of epileptic tissue during SLE but were similar in 0Mg and 0Mg+BMI. GABAergic facilitation of spectral “slow” oscillation and ripple correlations was most prominent within CA3 of epileptic tissue during SLE. When activity between regions was analyzed, slow oscillation and ripple coherence was highest between the hilus and dentate gyrus as well as between the hilus and CA3 of epileptic tissue during SLE and was significantly higher in 0Mg than 0Mg+BMI. High 0Mg-induced SLE cross-correlations between the hilus and dentate gyrus as well as between the hilus and CA3 were reduced or abolished in 0Mg+BMI. SLE cross-correlation lag measurements provided evidence for a monosynaptic connection from the hilus to the dentate gyrus during SLE. Findings implicate the hilus as an oscillation generator, whose impact on other cortico-hippocampal regions is mediated by GABAergic transmission. Data also suggest that GABAA receptor-mediated transmission facilitates back-propagation from CA3/hilus to the dentate gyrus and that this back-propagation augments SLE in epileptic hippocampus. PMID:23615549

CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life.

PubMed

Melani, Federico; Mei, Davide; Pisano, Tiziana; Savasta, Salvatore; Franzoni, Emilio; Ferrari, Anna Rita; Marini, Carla; Guerrini, Renzo

2011-04-01

Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition. We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23 mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions. One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic/vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus). Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures. © The Authors. Journal compilation © Mac Keith Press 2011.

Is there anything distinctive about epileptic deja vu?

PubMed

Warren-Gash, Charlotte; Zeman, Adam

2014-02-01

Déjà vu can occur as an aura of temporal lobe epilepsy and in some psychiatric conditions but is also common in the general population. It is unclear whether any clinical features distinguish pathological and physiological forms of déjà vu. 50 epileptic patients with ictal déjà vu, 50 non-epileptic patients attending general neurology clinics and 50 medical students at Edinburgh University were recruited. Data were collected on demographic factors, the experience of déjà vu using a questionnaire based on Sno's Inventory for Déjà Vu Experiences Assessment, symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale as well as seizure characteristics, anti-epileptic medications, handedness, EEG and neuroimaging findings for epileptic patients. 73.5% of neurology patients, 88% of students and (by definition) all epilepsy patients had experienced déjà vu. The experience of déjà vu itself was similar in the three groups. Epileptic déjà vu occurred more frequently and lasted somewhat longer than physiological déjà vu. Epilepsy patients were more likely to report prior fatigue and concentrated activity, associated derealisation, olfactory and gustatory hallucinations, physical symptoms such as headaches, abdominal sensations and fear. After controlling for study group, anxiety and depression scores were not associated with déjà vu frequency. Déjà vu is common and qualitatively similar whether it occurs as an epileptic aura or normal phenomenon. However ictal déjà vu occurs more frequently and is accompanied by several distinctive features. It is distinguished primarily by 'the company it keeps'.

Phenomenology of hallucinations, illusions, and delusions as part of seizure semiology.

PubMed

Kasper, B S; Kasper, E M; Pauli, E; Stefan, H

2010-05-01

In partial epilepsy, a localized hypersynchronous neuronal discharge evolving into a partial seizure affecting a particular cortical region or cerebral subsystem can give rise to subjective symptoms, which are perceived by the affected person only, that is, ictal hallucinations, illusions, or delusions. When forming the beginning of a symptom sequence leading to impairment of consciousness and/or a classic generalized seizure, these phenomena are referred to as an epileptic aura, but they also occur in isolation. They often manifest in the fully awake state, as part of simple partial seizures, but they also can be associated to different degrees of disturbed consciousness. Initial ictal symptoms often are closely related to the physiological functions of the cortical circuit involved and, therefore, can provide localizing information. When brain regions related to sensory integration are involved, the seizure discharge can cause specific kinds of hallucinations, for example, visual, auditory, gustatory, olfactory, and cutaneous sensory sensations. In addition to these elementary sensory perceptions, quite complex hallucinations related to a partial seizure can arise, for example, perception of visual scenes or hearing music. By involving psychic and emotional spheres of human perception, many seizures also give rise to hallucinatory emotional states (e.g., fear or happiness) or even more complex hallucinations (e.g., visuospatial phenomena), illusions (e.g., déjà vu, out-of-body experience), or delusional beliefs (e.g., identity change) that often are not easily recognized as epileptic. Here we suggest a classification into elementary sensory, complex sensory, and complex integratory seizure symptoms. Epileptic hallucinations, illusions, and delusions shine interesting light on the physiology and functional anatomy of brain regions involved and their functions in the human being. This article, in which 10 cases are described, introduces the fascinating phenomenology of subjective seizure symptoms. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures

PubMed Central

LaFrance, W.C.; Leaver, K.; Stopa, E.G.; Papandonatos, G.D.; Blum, A.S.

2010-01-01

Objective: Neurotrophins promote neurogenesis and help regulate synaptic reorganization. Their dysregulation has been implicated in a number of neurologic and psychiatric disorders. Previous studies have shown decreased levels of brain-derived neurotrophic factor (BDNF) in the serum of patients with psychiatric disorders such as major depressive disorder (MDD) and conversion disorder (CD). In human patients with temporal lobe epilepsy, there is an increase in both BDNF mRNA and protein levels in surgically resected hippocampi compared to controls. One study of children with epilepsy has found normal to increased serum BDNF levels compared to controls. Serum BDNF levels have not been investigated in adult patients with epileptic seizures (ES). We hypothesized that BDNF would differentiate between ES and psychogenic nonepileptic seizures (PNES). Methods: We assessed serum BDNF immunoreactivity in 15 patients with ES, 12 patients with PNES, and 17 healthy volunteers. Serum BDNF levels were measured using an enzyme-linked immunoassay. Results: Healthy controls showed higher BDNF levels (4,289 ± 1,810 pg/mL) compared to patients with PNES (1,033 ± 435 pg/mL) (p < 0.001). However, unexpectedly, healthy controls also showed higher levels of BDNF compared to patients with ES without comorbid MDD (977 ± 565 pg/mL) (p < 0.001). Conclusions: Unlike children, adults with epilepsy appear to have decreased levels of serum BDNF. Reduced serum BDNF levels can be used to differentiate adult patients with ES or PNES from healthy controls. Further human studies are needed to better understand the pathophysiology explaining the decreased serum BDNF levels found in epilepsy and in PNES. GLOSSARY AED = antiepileptic drug; BDI-II = Beck Depression Inventory II; BDNF = brain-derived neurotrophic factor; CD = conversion disorder; ECS = electroconvulsive seizure; ES = epileptic seizure; GTC = generalized tonic-clonic seizure; HC = healthy control; MDD = major depressive disorder; PNES = psychogenic nonepileptic seizure; PRL = prolactin; RIH = Rhode Island Hospital. PMID:20921514

Human photosensitivity: from pathophysiology to treatment.

PubMed

Verrotti, A; Tocco, A M; Salladini, C; Latini, G; Chiarelli, F

2005-11-01

Photosensitivity is a condition detected on the electroencephalography (EEG) as a paroxysmal reaction to Intermittent Photic Stimulation (IPS). This EEG response, elicited by IPS or by other visual stimuli of daily life, is called Photo Paroxysmal Response (PPR). PPRs are well documented in epileptic and non-epileptic subjects. Photosensitivity rarely in normal individuals evolves into epilepsy. Photosensitive epilepsy is a rare refex epilepsy characterized by seizures in photosensitive individuals. The development of modern technology has increased the exposition to potential seizure precipitants in people of all ages, but especially in children and adolescents. Actually, videogames, computers and televisions are the most common triggers in daily life of susceptible persons. The mechanisms of generation of PPR are poorly understood, but genetic factors play an important rule. The control of visually induced seizures has, generally a good prognosis. In patients known to be visually sensitive, avoidance of obvious source and stimulus modifications are very important and useful to seizure prevention, but in the large majority of patients with epilepsy and photosensitivity antiepileptic drugs are needed.

Fuzzy topological digital space and digital fuzzy spline of electroencephalography during epileptic seizures

NASA Astrophysics Data System (ADS)

Shah, Mazlina Muzafar; Wahab, Abdul Fatah

2017-08-01

Epilepsy disease occurs because of there is a temporary electrical disturbance in a group of brain cells (nurons). The recording of electrical signals come from the human brain which can be collected from the scalp of the head is called Electroencephalography (EEG). EEG then considered in digital format and in fuzzy form makes it a fuzzy digital space data form. The purpose of research is to identify the area (curve and surface) in fuzzy digital space affected by inside epilepsy seizure in epileptic patient's brain. The main focus for this research is to generalize fuzzy topological digital space, definition and basic operation also the properties by using digital fuzzy set and the operations. By using fuzzy digital space, the theory of digital fuzzy spline can be introduced to replace grid data that has been use previously to get better result. As a result, the flat of EEG can be fuzzy topological digital space and this type of data can be use to interpolate the digital fuzzy spline.

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures

PubMed Central

Heise, Christopher; Taha, Elham; Murru, Luca; Ponzoni, Luisa; Cattaneo, Angela; Guarnieri, Fabrizia C.; Montani, Caterina; Mossa, Adele; Vezzoli, Elena; Ippolito, Giulio; Zapata, Jonathan; Barrera, Iliana; Ryazanov, Alexey G.; Cook, James; Poe, Michael; Stephen, Michael Rajesh; Kopanitsa, Maksym; Benfante, Roberta; Rusconi, Francesco; Braida, Daniela; Francolini, Maura; Proud, Christopher G.; Valtorta, Flavia; Passafaro, Maria; Sala, Mariaelvina; Bachi, Angela; Verpelli, Chiara; Rosenblum, Kobi; Sala, Carlo

2017-01-01

Abstract Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. PMID:27005990

Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy

PubMed Central

Khambhati, Ankit N.; Davis, Kathryn A.; Oommen, Brian S.; Chen, Stephanie H.; Lucas, Timothy H.; Litt, Brian; Bassett, Danielle S.

2015-01-01

The epileptic network is characterized by pathologic, seizure-generating ‘foci’ embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci—a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices. PMID:26680762

Degenerate time-dependent network dynamics anticipate seizures in human epileptic brain.

PubMed

Tauste Campo, Adrià; Principe, Alessandro; Ley, Miguel; Rocamora, Rodrigo; Deco, Gustavo

2018-04-01

Epileptic seizures are known to follow specific changes in brain dynamics. While some algorithms can nowadays robustly detect these changes, a clear understanding of the mechanism by which these alterations occur and generate seizures is still lacking. Here, we provide crossvalidated evidence that such changes are initiated by an alteration of physiological network state dynamics. Specifically, our analysis of long intracranial electroencephalography (iEEG) recordings from a group of 10 patients identifies a critical phase of a few hours in which time-dependent network states become less variable ("degenerate"), and this phase is followed by a global functional connectivity reduction before seizure onset. This critical phase is characterized by an abnormal occurrence of highly correlated network instances and is shown to be particularly associated with the activity of the resected regions in patients with validated postsurgical outcome. Our approach characterizes preseizure network dynamics as a cascade of 2 sequential events providing new insights into seizure prediction and control.

Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy.

PubMed

Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

2015-01-01

The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration.

Epilepsy is Dancing.

PubMed

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.

Novel images extraction model using improved delay vector variance feature extraction and multi-kernel neural network for EEG detection and prediction.

PubMed

Ge, Jing; Zhang, Guoping

2015-01-01

Advanced intelligent methodologies could help detect and predict diseases from the EEG signals in cases the manual analysis is inefficient available, for instance, the epileptic seizures detection and prediction. This is because the diversity and the evolution of the epileptic seizures make it very difficult in detecting and identifying the undergoing disease. Fortunately, the determinism and nonlinearity in a time series could characterize the state changes. Literature review indicates that the Delay Vector Variance (DVV) could examine the nonlinearity to gain insight into the EEG signals but very limited work has been done to address the quantitative DVV approach. Hence, the outcomes of the quantitative DVV should be evaluated to detect the epileptic seizures. To develop a new epileptic seizure detection method based on quantitative DVV. This new epileptic seizure detection method employed an improved delay vector variance (IDVV) to extract the nonlinearity value as a distinct feature. Then a multi-kernel functions strategy was proposed in the extreme learning machine (ELM) network to provide precise disease detection and prediction. The nonlinearity is more sensitive than the energy and entropy. 87.5% overall accuracy of recognition and 75.0% overall accuracy of forecasting were achieved. The proposed IDVV and multi-kernel ELM based method was feasible and effective for epileptic EEG detection. Hence, the newly proposed method has importance for practical applications.

Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

PubMed

Jiruska, Premysl; Proks, Jan; Otáhal, Jakub; Mares, Pavel

2007-10-01

Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.

Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A.

PubMed

Mathew, Jobin; Peeyush Kumar, T; Khan, Reas S; Paulose, C S

2010-04-01

In the present study, the effects of Bacopa monnieri and its active component, bacoside A, on motor deficit and alterations of GABA receptor functional regulation in the cerebellum of epileptic rats were investigated. Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the cerebellum of epileptic rats revealed a significant decrease in B(max) compared with control. Real-time polymerase chain reaction amplification of GABA(A) receptor subunits-GABA(Aalpha1), GABA(Aalpha5,) and GABA(Adelta)-was downregulated (P<0.001) in the cerebellum of epileptic rats compared with control rats. Epileptic rats exhibit deficits in radial arm and Y-maze performance. Treatment with B. monnieri and bacoside A reversed these changes to near-control levels. Our results suggest that changes in GABAergic activity, motor learning, and memory deficit are induced by the occurrence of repetitive seizures. Treatment with B. monnieri and bacoside A prevents the occurrence of seizures thereby reducing the impairment of GABAergic activity, motor learning, and memory deficit. Copyright (c) 2010 Elsevier Inc. All rights reserved.

A comparative study of a theoretical neural net model with MEG data from epileptic patients and normal individuals.

PubMed

Kotini, A; Anninos, P; Anastasiadis, A N; Tamiolakis, D

2005-09-07

The aim of this study was to compare a theoretical neural net model with MEG data from epileptic patients and normal individuals. Our experimental study population included 10 epilepsy sufferers and 10 healthy subjects. The recordings were obtained with a one-channel biomagnetometer SQUID in a magnetically shielded room. Using the method of x2-fitting it was found that the MEG amplitudes in epileptic patients and normal subjects had Poisson and Gauss distributions respectively. The Poisson connectivity derived from the theoretical neural model represents the state of epilepsy, whereas the Gauss connectivity represents normal behavior. The MEG data obtained from epileptic areas had higher amplitudes than the MEG from normal regions and were comparable with the theoretical magnetic fields from Poisson and Gauss distributions. Furthermore, the magnetic field derived from the theoretical model had amplitudes in the same order as the recorded MEG from the 20 participants. The approximation of the theoretical neural net model with real MEG data provides information about the structure of the brain function in epileptic and normal states encouraging further studies to be conducted.

Models for discovery of targeted therapy in genetic epileptic encephalopathies.

PubMed

Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

Independent Neuronal Origin of Seizures and Behavioral Comorbidities in an Animal Model of a Severe Childhood Genetic Epileptic Encephalopathy

PubMed Central

Asinof, Samuel K.; Sukoff Rizzo, Stacey J.; Buckley, Alexandra R.; Beyer, Barbara J.; Letts, Verity A.; Frankel, Wayne N.; Boumil, Rebecca M.

2015-01-01

The childhood epileptic encephalopathies (EE’s) are seizure disorders that broadly impact development including cognitive, sensory and motor progress with severe consequences and comorbidities. Recently, mutations in DNM1 (dynamin 1) have been implicated in two EE syndromes, Lennox-Gastaut Syndrome and Infantile Spasms. Dnm1 encodes dynamin 1, a large multimeric GTPase necessary for activity-dependent membrane recycling in neurons, including synaptic vesicle endocytosis. Dnm1Ftfl or “fitful” mice carry a spontaneous mutation in the mouse ortholog of DNM1 and recapitulate many of the disease features associated with human DNM1 patients, providing a relevant disease model of human EE’s. In order to examine the cellular etiology of seizures and behavioral and neurological comorbidities, we engineered a conditional Dnm1Ftfl mouse model of DNM1 EE. Observations of Dnm1 Ftfl/flox mice in combination with various neuronal subpopulation specific cre strains demonstrate unique seizure phenotypes and clear separation of major neurobehavioral comorbidities from severe seizures associated with the germline model. This demonstration of pleiotropy suggests that treating seizures per se may not prevent severe comorbidity observed in EE associated with dynamin-1 mutations, and is likely to have implications for other genetic forms of EE. PMID:26125563

Long-term variability of importance of brain regions in evolving epileptic brain networks

NASA Astrophysics Data System (ADS)

Geier, Christian; Lehnertz, Klaus

2017-04-01

We investigate the temporal and spatial variability of the importance of brain regions in evolving epileptic brain networks. We construct these networks from multiday, multichannel electroencephalographic data recorded from 17 epilepsy patients and use centrality indices to assess the importance of brain regions. Time-resolved indications of highest importance fluctuate over time to a greater or lesser extent, however, with some periodic temporal structure that can mostly be attributed to phenomena unrelated to the disease. In contrast, relevant aspects of the epileptic process contribute only marginally. Indications of highest importance also exhibit pronounced alternations between various brain regions that are of relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches. Nonetheless, these findings may guide new developments for individualized diagnosis, treatment, and control.

[Consciousness and the electroencephalogram].

PubMed

Faber, J; Vladyka, V; Subrt, O

1991-08-01

In the course of 12 years the authors subjected to clinical EEG and stereo-EEG (SEEG) 72 patients (66 epileptics with the diagnosis of psychomotor epilepsy and grand mal) and six psychotic patients suffering from schizophrenia. With the exception of five epileptics and two psychotic patients all subjects had epileptic foci in the amygdalohippocampal complex (AHK). After coagulation of these foci marked improvement of the fits and the mental state occurred in half the patients. During EEG and SEEG recording the authors used different activation methods (hyperventilation through the nose and mouth, sleep, listening to music) and above all direct electric stimulation (ES) of one of the AHK. Secondary epileptic foci had, as a rule, more spikes and a lower threshold for ES than primary ones which contained more delta and slow theta waves. The ES led as a rule to an emotional response, such as anxiety and fear, more rarely to illusions, depersonalization and oneiroid hallucinations and twice to a hedonic response of non-sexual character. The purpose of ES was to assess the site from where it is possible to start the original aura or typical parox. The authors considered these foci, consistent with data in the literature, as the leading focus and it was subsequently coagulated. The authors investigated the reactivity and vigility by the patient's response to sound (the patient had to press a button) and by an interview with the patient. It was revealed that in isolated discharges of the spikes and waves in the scalp electrodes, i.e. in the neocortex, reactivity is lacking. In isolated discharges in the AHK the reactivity was satisfactory, but as a rule anxiety developed. It is thus possible to divide consciousness into emotional consciousness with its site in the AHK, i.e. in the limbic system, and rational consciousness which is a function of the neocrotical system. Congenital changes of consciousness such as vigility or sleep are described as "states" of consciousness. The rational or emotional aspect of behaviour is described as "type" of consciousness. Under normal conditions the states of consciousness alternate periodically and are sharply defined, the types of consciousness are closely linked and are difficult to separate. Under pathological conditions the "states" of consciousness differ less markedly and the "types" of consciousness are in dissociation. Thus obnubilation, depersonalization, illusions, pathic affects etc. develop, as a rule as part of the epileptiform or psychotiform syndrome.

Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy

PubMed Central

Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

2015-01-01

The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration. PMID:27081548

[Epilepsy and videogame: which physiopathological mechanisms to expect?].

PubMed

Masnou, P; Nahum-Moscovoci, L

1999-04-01

Video games may induce epileptic seizures in some subjects. Most of them have photosensitive epilepsy. The triggering factors are multiple: characteristics of the softwares, effects of the electronic screen and interactivity. The wide diffusion of the video games explain the large number of descriptions of videogame induced seizures. Historical aspects and an analysis of the underlying mechanisms of videogame induced seizures are presented.

Epilepsy, cognition and behavior.

PubMed

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.

Distribution entropy analysis of epileptic EEG signals.

PubMed

Li, Peng; Yan, Chang; Karmakar, Chandan; Liu, Changchun

2015-01-01

It is an open-ended challenge to accurately detect the epileptic seizures through electroencephalogram (EEG) signals. Recently published studies have made elaborate attempts to distinguish between the normal and epileptic EEG signals by advanced nonlinear entropy methods, such as the approximate entropy, sample entropy, fuzzy entropy, and permutation entropy, etc. Most recently, a novel distribution entropy (DistEn) has been reported to have superior performance compared with the conventional entropy methods for especially short length data. We thus aimed, in the present study, to show the potential of DistEn in the analysis of epileptic EEG signals. The publicly-accessible Bonn database which consisted of normal, interictal, and ictal EEG signals was used in this study. Three different measurement protocols were set for better understanding the performance of DistEn, which are: i) calculate the DistEn of a specific EEG signal using the full recording; ii) calculate the DistEn by averaging the results for all its possible non-overlapped 5 second segments; and iii) calculate it by averaging the DistEn values for all the possible non-overlapped segments of 1 second length, respectively. Results for all three protocols indicated a statistically significantly increased DistEn for the ictal class compared with both the normal and interictal classes. Besides, the results obtained under the third protocol, which only used very short segments (1 s) of EEG recordings showed a significantly (p <; 0.05) increased DistEn for the interictal class in compassion with the normal class, whereas both analyses using relatively long EEG signals failed in tracking this difference between them, which may be due to a nonstationarity effect on entropy algorithm. The capability of discriminating between the normal and interictal EEG signals is of great clinical relevance since it may provide helpful tools for the detection of a seizure onset. Therefore, our study suggests that the DistEn analysis of EEG signals is very promising for clinical and even portable EEG monitoring.

Chronic agomelatine treatment prevents comorbid depression in the post-status epilepticus model of acquired epilepsy through suppression of inflammatory signaling.

PubMed

Tchekalarova, Jana; Atanasova, Dimitrinka; Kortenska, Lidia; Atanasova, Milena; Lazarov, Nikolai

2018-07-01

Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. In the present study, we tested the hypothesis that the novel antidepressant agomelatine, a potent melatonin MT 1 and MT 2 receptor agonist and serotonin 5HT 2C receptor antagonist, can prevent depressive symptoms developed during the chronic epileptic phase by suppressing an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.p.) was initiated an hour after the kainate acid (KA)-induced status epilepticus (SE) and maintained for a period of 10 weeks in Wistar rats. Registration of spontaneous motor seizures was performed through a video (24 h/day) and EEG monitoring. Antidepressant activity of agomelatine was explored in the splash test, sucrose preference test (SPT) and forced swimming test (FST) while anxiolytic effect was observed through the novelty suppression-feeding test (NSFT) during chronic phase in epileptic rats. The frequency of motor seizures detected by video and EEG recording did not differ between vehicle and Ago group. Rats with registered spontaneous motor seizures showed symptoms typical for depressive behavior that included decreased grooming, anhedonia during the dark period and hopeless-like behavior. Epileptic rats exhibited also anxiety with novelty-induced hypophagia. This behavioral deficit correlated with increased signal markers of inflammation (plasma levels of interleukin (IL)-1β and activated glia in brain), while plasma corticosterone levels were not changed. Agomelatine treatment during epileptogenesis exerted a clear antidepressant effect by suppressing all behavioral hallmarks, reducing plasma IL-1β levels and preventing microgliosis and astrogliosis in specific limbic regions. The present results suggest that agomelatine treatment starting after SE can provide an effective therapy of comorbid depression in chronic epileptic condition through suppression of inflammatory signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-term variability of global statistical properties of epileptic brain networks

NASA Astrophysics Data System (ADS)

Kuhnert, Marie-Therese; Elger, Christian E.; Lehnertz, Klaus

2010-12-01

We investigate the influence of various pathophysiologic and physiologic processes on global statistical properties of epileptic brain networks. We construct binary functional networks from long-term, multichannel electroencephalographic data recorded from 13 epilepsy patients, and the average shortest path length and the clustering coefficient serve as global statistical network characteristics. For time-resolved estimates of these characteristics we observe large fluctuations over time, however, with some periodic temporal structure. These fluctuations can—to a large extent—be attributed to daily rhythms while relevant aspects of the epileptic process contribute only marginally. Particularly, we could not observe clear cut changes in network states that can be regarded as predictive of an impending seizure. Our findings are of particular relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches.

Decreased GABA receptor in the striatum and spatial recognition memory deficit in epileptic rats: effect of Bacopa monnieri and bacoside-A.

PubMed

Mathew, Jobin; Soman, Smijin; Sadanandan, Jayanarayanan; Paulose, Cheramadathikudyil Skaria

2010-07-20

Gamma-aminobutyric acid A receptors are the principal mediators of synaptic inhibition in striatal neurons and play an important role in preventing the spreading of seizures through the striatum. In the present study, effect of Bacopa monnieri (L.) Pennel and its active component bacoside-A on spatial recognition memory deficit and alterations of GABA receptor in the striatum of epileptic rats were investigated. Total GABA and GABA(A) receptor numbers in the control and epileptic rats were evaluated using [(3)H]GABA and [(3)H]bicuculline binding. GABA(Aalpha1,) GABA(Aalpha5,) GABA(Agamma3) and GABA(Adelta) gene expressions were studied. Behavioral performance was assed using Y-maze. Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the striatum of epileptic rats showed significant decrease in B(max) compared to control. Real-Time PCR amplification of GABA(A) receptor subunits such as GABA(Aalpha1,) GABA(Aalpha5) and GABA(Adelta), were down regulated (p<0.001) in the striatum of epileptic rats compared to control. Epileptic rats have deficit in Y-maze performance. Bacopa monnieri and bacoside-A treatment reversed these changes to near control. Our results suggest that decreased GABA receptors in the striatum have an important role in epilepsy associated motor learning deficits and Bacopa monnieri and bacoside-A has a beneficial effect in the management of epilepsy. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves

PubMed Central

von Ellenrieder, Nicolás; Ferrari-Marinho, Taissa; Avoli, Massimo; Dubeau, François; Gotman, Jean

2015-01-01

Epileptic discharges in focal epilepsy are frequently activated during non-rapid eye movement sleep. Sleep slow waves are present during this stage and have been shown to include a deactivated (‘down’, hyperpolarized) and an activated state (‘up’, depolarized). The ‘up’ state enhances physiological rhythms, and we hypothesize that sleep slow waves and particularly the ‘up’ state are the specific components of non-rapid eye movement sleep that mediate the activation of epileptic activity. We investigated eight patients with pharmaco-resistant focal epilepsies who underwent combined scalp-intracerebral electroencephalography for diagnostic evaluation. We analysed 259 frontal electroencephalographic channels, and manually marked 442 epileptic spikes and 8487 high frequency oscillations during high amplitude widespread slow waves, and during matched control segments with low amplitude widespread slow waves, non-widespread slow waves or no slow waves selected during the same sleep stages (total duration of slow wave and control segments: 49 min each). During the slow waves, spikes and high frequency oscillations were more frequent than during control segments (79% of spikes during slow waves and 65% of high frequency oscillations, both P ∼ 0). The spike and high frequency oscillation density also increased for higher amplitude slow waves. We compared the density of spikes and high frequency oscillations between the ‘up’ and ‘down’ states. Spike and high frequency oscillation density was highest during the transition from the ‘up’ to the ‘down’ state. Interestingly, high frequency oscillations in channels with normal activity expressed a different peak at the transition from the ‘down’ to the ‘up’ state. These results show that the apparent activation of epileptic discharges by non-rapid eye movement sleep is not a state-dependent phenomenon but is predominantly associated with specific events, the high amplitude widespread slow waves that are frequent, but not continuous, during this state of sleep. Both epileptic spikes and high frequency oscillations do not predominate, like physiological activity, during the ‘up’ state but during the transition from the ‘up’ to the ‘down’ state of the slow wave, a period of high synchronization. Epileptic discharges appear therefore more associated with synchronization than with excitability. Furthermore, high frequency oscillations in channels devoid of epileptic activity peak differently during the slow wave cycle from those in channels with epileptic activity. This property may allow differentiating physiological from pathological high frequency oscillations, a problem that is unresolved until now. PMID:25792528

Synchronization of hyperexcitable systems with phase-repulsive coupling

NASA Astrophysics Data System (ADS)

Balázsi, Gábor; Cornell-Bell, Ann; Neiman, Alexander B.; Moss, Frank

2001-10-01

We study two-dimensional arrays of FitzHugh-Nagumo elements with nearest-neighbor coupling from the viewpoint of synchronization. The elements are diffusively coupled. By varying the diffusion coefficient from positive to negative values, interesting synchronization patterns are observed. The results of the simulations resemble the intracellular oscillation patterns observed in cultured human epileptic astrocytes. Three measures are proposed to determine the degree of synchronization (or coupling) in both the simulated and the experimental system.

Determination of the R(-) and S(+)-enantiomers of vigabatrin in human plasma by ultra-high-performance liquid chromatography and tandem mass-spectrometry.

PubMed

Duhamel, Paul; Ounissi, Marwa; Le Saux, Thomas; Bienayme, Hugues; Chiron, Catherine; Jullien, Vincent

2017-12-01

An analytical method was developed for the quantification in plasma of the R and S enantiomers of vigabatrin (VGB), a drug used for the treatment of some refractory pediatric epileptic syndromes. After adding 50μL of the internal standard, which consisted of a 15mg/L solution of deuterated racemic VGB, and 100μL of water to 100μL of plasma samples, a protein precipitation was performed by adding 600μL of methanol. The supernatant was evaporated to dryness under a stream of nitrogen and the dry residue was reconstituted with 500μL of water. Then, 100μL of 0.01M o-phthaldialdehyde and 0.01M N-acetyl-l-cysteine in borate buffer (0.1M, pH=9.5) were added for pre-column derivatization of the enantiomers as diastereomeric isoindoles. One microliter of the resulting mixture was injected in the chromatographic system. The chromatographic separation was performed in gradient elution mode at a flow rate of 400μL/min using a phenomenex EVO C-18 column with a mobile phase composed of 5mM ammonium acetate and a methanol:acetonitrile (63:37v/v) mixture. Detection was performed by mass spectrometry in selected reaction monitoring mode using heated electrospray ionization in positive mode as the ion source. Intra- and inter-day precision and accuracy were lower than 15% over the calibration range (0.2-50mg/L for each enantiomer) and the method was successfully used to assess plasma concentrations of VGB in epileptic children. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

PubMed Central

Murta, Teresa; Leite, Marco; Carmichael, David W; Figueiredo, Patrícia; Lemieux, Louis

2015-01-01

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. PMID:25277370

Using patient-specific hemodynamic response function in epileptic spike analysis of human epilepsy: a study based on EEG-fNIRS.

PubMed

Peng, Ke; Nguyen, Dang Khoa; Vannasing, Phetsamone; Tremblay, Julie; Lesage, Frédéric; Pouliot, Philippe

2016-02-01

Functional near-infrared spectroscopy (fNIRS) can be combined with electroencephalography (EEG) to continuously monitor the hemodynamic signal evoked by epileptic events such as seizures or interictal epileptiform discharges (IEDs, aka spikes). As estimation methods assuming a canonical shape of the hemodynamic response function (HRF) might not be optimal, we sought to model patient-specific HRF (sHRF) with a simple deconvolution approach for IED-related analysis with EEG-fNIRS data. Furthermore, a quadratic term was added to the model to account for the nonlinearity in the response when IEDs are frequent. Prior to analyzing clinical data, simulations were carried out to show that the HRF was estimable by the proposed deconvolution methods under proper conditions. EEG-fNIRS data of five patients with refractory focal epilepsy were selected due to the presence of frequent clear IEDs and their unambiguous focus localization. For each patient, both the linear sHRF and the nonlinear sHRF were estimated at each channel. Variability of the estimated sHRFs was seen across brain regions and different patients. Compared with the SPM8 canonical HRF (cHRF), including these sHRFs in the general linear model (GLM) analysis led to hemoglobin activations with higher statistical scores as well as larger spatial extents on all five patients. In particular, for patients with frequent IEDs, nonlinear sHRFs were seen to provide higher sensitivity in activation detection than linear sHRFs. These observations support using sHRFs in the analysis of IEDs with EEG-fNIRS data. Copyright © 2015 Elsevier Inc. All rights reserved.

Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

PubMed Central

Wolfart, Jakob; Laker, Debora

2015-01-01

Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

Epileptic spasms are a feature of DEPDC5 mTORopathy

PubMed Central

Carvill, Gemma L.; Crompton, Douglas E.; Regan, Brigid M.; McMahon, Jacinta M.; Saykally, Julia; Zemel, Matthew; Schneider, Amy L.; Dibbens, Leanne; Howell, Katherine B.; Mandelstam, Simone; Leventer, Richard J.; Harvey, A. Simon; Mullen, Saul A.; Berkovic, Samuel F.; Sullivan, Joseph; Scheffer, Ingrid E.

2015-01-01

Objective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. Conclusions: While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies. PMID:27066554

Multimodality localization of epileptic foci

NASA Astrophysics Data System (ADS)

Desco, Manuel; Pascau, Javier; Pozo, M. A.; Santos, Andres; Reig, Santiago; Gispert, Juan D.; Garcia-Barreno, Pedro

2001-05-01

This paper presents a multimodality approach for the localization of epileptic foci using PET, MRI and EEG combined without the need of external markers. Mutual Information algorithm is used for MRI-PET registration. Dipole coordinates (provided by BESA software) are projected onto the MRI using a specifically developed algorithm. The four anatomical references used for electrode positioning (nasion, inion and two preauricular points) are located on the MRI using a triplanar viewer combined with a surface-rendering tool. Geometric transformation using deformation of the ideal sphere used for dipole calculations is then applied to match the patient's brain size and shape. Eight treatment-refractory epileptic patients have been studied. The combination of the anatomical information from the MRI, hipoperfusion areas in PET and dipole position and orientation helped the physician in the diagnosis of epileptic focus location. Neurosurgery was not indicated for patients where PET and dipole results were inconsistent; in two cases it was clinically indicated despite the mismatch, showing a negative follow up. The multimodality approach presented does not require external markers for dipole projection onto the MRI, this being the main difference with previous methods. The proposed method may play an important role in the indication of surgery for treatment- refractory epileptic patients.

Epileptic Seizures Prediction Using Machine Learning Methods

PubMed Central

Usman, Syed Muhammad

2017-01-01

Epileptic seizures occur due to disorder in brain functionality which can affect patient's health. Prediction of epileptic seizures before the beginning of the onset is quite useful for preventing the seizure by medication. Machine learning techniques and computational methods are used for predicting epileptic seizures from Electroencephalograms (EEG) signals. However, preprocessing of EEG signals for noise removal and features extraction are two major issues that have an adverse effect on both anticipation time and true positive prediction rate. Therefore, we propose a model that provides reliable methods of both preprocessing and feature extraction. Our model predicts epileptic seizures' sufficient time before the onset of seizure starts and provides a better true positive rate. We have applied empirical mode decomposition (EMD) for preprocessing and have extracted time and frequency domain features for training a prediction model. The proposed model detects the start of the preictal state, which is the state that starts few minutes before the onset of the seizure, with a higher true positive rate compared to traditional methods, 92.23%, and maximum anticipation time of 33 minutes and average prediction time of 23.6 minutes on scalp EEG CHB-MIT dataset of 22 subjects. PMID:29410700

How Sleep Activates Epileptic Networks?

PubMed Central

Halász, Peter

2013-01-01

Background. The relationship between sleep and epilepsy has been long ago studied, and several excellent reviews are available. However, recent development in sleep research, the network concept in epilepsy, and the recognition of high frequency oscillations in epilepsy and more new results may put this matter in a new light. Aim. The review address the multifold interrelationships between sleep and epilepsy networks and with networks of cognitive functions. Material and Methods. The work is a conceptual update of the available clinical data and relevant studies. Results and Conclusions. Studies exploring dynamic microstructure of sleep have found important gating mechanisms for epileptic activation. As a general rule interictal epileptic manifestations seem to be linked to the slow oscillations of sleep and especially to the reactive delta bouts characterized by A1 subtype in the CAP system. Important link between epilepsy and sleep is the interference of epileptiform discharges with the plastic functions in NREM sleep. This is the main reason of cognitive impairment in different forms of early epileptic encephalopathies affecting the brain in a special developmental window. The impairment of cognitive functions via sleep is present especially in epileptic networks involving the thalamocortical system and the hippocampocortical memory encoding system. PMID:24159386

[Unusual dreams in epileptics].

PubMed

Boldyrev, A I

1984-01-01

The author discusses bizarre dreams characteristic of epileptics and never occurring in normal subjects which have an important practical implication especially for early detection of epilepsy and the prevention of severe forms of the disease. This group of dreams includes vivid nightmares with vital fear, dreams not infrequently transforming into pro-dream states; persistently repeated stereotyped dreams and dreams with invariably the same unpleasant sensations representing an isolated aura of subsequent epileptic attacks. Diagnostically important may also be dreams with the symptoms of derealization and depersonalization, vague dream images and the deja vu phenomenon.

Transient epileptic amnesia: clinical report of a cohort of patients.

PubMed

Lapenta, Leonardo; Brunetti, Valerio; Losurdo, Anna; Testani, Elisa; Giannantoni, Nadia Mariagrazia; Quaranta, Davide; Di Lazzaro, Vincenzo; Della Marca, Giacomo

2014-07-01

Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients.

A note on a phrase in Shakespeare's play King Lear: 'a plague upon your epileptic visage'.

PubMed

Betts, T; Betts, H

1998-10-01

In Shakespeare's play King Lear the word 'epileptic' appears (used in a derogatory manner). This is held to be the first appearance of the word in the English language (although we have found earlier English references to the word which Shakespeare may have read). Textual analysis of the lines following the use of 'epileptic' suggests that it is actually a reference to the pock-marks of syphilis, endemic in Elizabethan England, and is not actually a reference to epilepsy itself.

Classification of ictal and seizure-free HRV signals with focus on lateralization of epilepsy.

PubMed

Behbahani, Soroor; Dabanloo, Nader Jafarnia; Nasrabadi, Ali Motie; Dourado, Antonio

2016-01-01

Epileptic onsets often affect the autonomic function of the body during a seizure, whether it is in ictal, interictal or post-ictal periods. The different effects of localization and lateralization of seizures on heart rate variability (HRV) emphasize the importance of autonomic function changes in epileptic patients. On the other hand, the detection of seizures is of primary interests in evaluating the epileptic patients. In the current paper, we analyzed the HRV signal to develop a reliable offline seizure-detection algorithm to focus on the effects of lateralization on HRV. We assessed the HRV during 5-min segments of continuous electrocardiogram (ECG) recording with a total number of 170 seizures occurred in 16 patients, composed of 86 left-sided and 84 right-sided focus seizures. Relatively high and low-frequency components of the HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series considered as non-linear features. We fed these features to the Support Vector Machines (SVMs) to find a robust classification method to classify epileptic and non-epileptic signals. Leave One Out Cross-Validation (LOOCV) approach was used to demonstrate the consistency of the classification results. Our obtained classification accuracy confirms that the proposed scheme has a potential in classifying HRV signals to epileptic and non-epileptic classes. The accuracy rates for right-sided and left-sided focus seizures were obtained as 86.74% and 79.41%, respectively. The main finding of our study is that the patients with right-sided focus epilepsy showed more reduction in parasympathetic activity and more increase in sympathetic activity. It can be a marker of impaired vagal activity associated with increased cardiovascular risk and arrhythmias. Our results suggest that lateralization of the seizure onset zone could exert different influences on heart rate changes. A right-sided seizure would cause an ictal tachycardia whereas a left-sided seizure would result in an ictal bradycardia.

The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: a moderated mediation analysis.

PubMed

Chung, Man Cheung; Allen, Rachel D; Dennis, Ian

2013-12-30

This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas. © 2013 Elsevier Ireland Ltd. All rights reserved.

The management of epilepsy in pregnancy at the Whittington Hospital: a retrospective audit 2004–2006 and 2007–2010

PubMed Central

Allen, Rebecca; Grosu, Liliana; Das, Ishita; Kyei-Mensah, Amma

2013-01-01

Background: In the last maternal death enquiries report there were 14 indirect deaths due to epilepsy. Methods: Retrospective case-note analysis of epileptic women seen antenatally over two separate time periods were examined. Care in the routine antenatal clinic (ANC) was compared with that in the obstetric medicine clinic (OMC). Results: 1st audit, 65 epileptic women seen. In OMC 14% had documented preconception counselling, 58% were on anti-epileptic drugs (AEDs). In ANC 0% had documented preconception counselling, 34% were on AEDs. 2nd audit, 88 epileptic women seen. In OMC 37.5% of women had preconception counselling, 84% were on AEDs. In ANC, 4.2% had preconception counselling, 31% were on AEDs. Conclusions: Women seen in OMC received care more compliant with Scottish Obstetric Group and Audit Project recommendations. All women with epilepsy should be reviewed in an OMC. PMID:27757160

An epileptic seizures detection algorithm based on the empirical mode decomposition of EEG.

PubMed

Orosco, Lorena; Laciar, Eric; Correa, Agustina Garces; Torres, Abel; Graffigna, Juan P

2009-01-01

Epilepsy is a neurological disorder that affects around 50 million people worldwide. The seizure detection is an important component in the diagnosis of epilepsy. In this study, the Empirical Mode Decomposition (EMD) method was proposed on the development of an automatic epileptic seizure detection algorithm. The algorithm first computes the Intrinsic Mode Functions (IMFs) of EEG records, then calculates the energy of each IMF and performs the detection based on an energy threshold and a minimum duration decision. The algorithm was tested in 9 invasive EEG records provided and validated by the Epilepsy Center of the University Hospital of Freiburg. In 90 segments analyzed (39 with epileptic seizures) the sensitivity and specificity obtained with the method were of 56.41% and 75.86% respectively. It could be concluded that EMD is a promissory method for epileptic seizure detection in EEG records.

Physics of the Brain. Prevention of the Epileptic Seizures by the Multi-photon Pulsed-operated Fiber Lasers in the Ultraviolet Range of Frequencies.

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander; IAPS Team

The novel study of the epileptogenesis mechanisms is proposed. It is based on the pulsed-operated (amplitude modulation) multi-photon (frequency modulation) fiber-laser interaction with the brain epilepsy-topion (the epilepsy onset area), so as to prevent the excessive electrical discharge (epileptic seizure) in the brain. The repetition frequency, Ω, matches the low frequency (epileptic) phonon waves in the brain. The laser repetition frequency (5-100 pulses per second) enables the resonance-scanning of the wide range of the phonon (possible epileptic-to-be) activity in the brain. The tunable fiber laser frequencies, Δω (multi photon operation), are in the ultraviolet frequency range, thus enabling monitoring of the electrical charge imbalance (within the 10s of milliseconds), and the DNA-corruption in the epilepsy-topion, as the possible cause of the disease. Supported by Nikola Tesla Labs., Stefan University.

Complementary treatment of psychotic and epileptic patients in malaysia.

PubMed

Razali, Salleh Mohd; Yassin, Azhar Mohd

2008-09-01

The objective of this article is to describe and compare the use of traditional/complementary medicine (T/CM) among psychotic (schizophrenia and schizophreniform disorder) and epileptic Malay patients in peninsular Malaysia. There were 60 patients in each group. T/CM consultation was uniformly spread across all levels of education and social status. We could not find a single over-riding factor that influenced the decision to seek T/CM treatment because the decision to seek such treatment was complex and the majority of decisions were made by others. Fifty-three patients (44.2%), consisting of 37 (61.7%) psychotic and 16 (26.7%) epileptic patients had consulted Malay traditional healers (bomoh) and/or homeopathic practitioners in addition to modern treatment; of these, only three had consulted bomoh and homeopathic practitioners at the same time. The use of T/CM was significantly higher in psychotic than in epileptic Malay patients.

Epileptic seizure classification of EEG time-series using rational discrete short-time fourier transform.

PubMed

Samiee, Kaveh; Kovács, Petér; Gabbouj, Moncef

2015-02-01

A system for epileptic seizure detection in electroencephalography (EEG) is described in this paper. One of the challenges is to distinguish rhythmic discharges from nonstationary patterns occurring during seizures. The proposed approach is based on an adaptive and localized time-frequency representation of EEG signals by means of rational functions. The corresponding rational discrete short-time Fourier transform (DSTFT) is a novel feature extraction technique for epileptic EEG data. A multilayer perceptron classifier is fed by the coefficients of the rational DSTFT in order to separate seizure epochs from seizure-free epochs. The effectiveness of the proposed method is compared with several state-of-art feature extraction algorithms used in offline epileptic seizure detection. The results of the comparative evaluations show that the proposed method outperforms competing techniques in terms of classification accuracy. In addition, it provides a compact representation of EEG time-series.

Two Novel Variants Affecting CDKL5 Transcript Associated with Epileptic Encephalopathy.

PubMed

Neupauerová, Jana; Štěrbová, Katalin; Vlčková, Markéta; Sebroňová, Věra; Maříková, Tat'ána; Krůtová, Marcela; David, Staněk; Kršek, Pavel; Žaliová, Markéta; Seeman, Pavel; Laššuthová, Petra

2017-10-01

Variants in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been reported as being etiologically associated with early infantile epileptic encephalopathy type 2 (EIEE2). We report on two patients, a boy and a girl, with EIEE2 that present with early onset epilepsy, hypotonia, severe intellectual disability, and poor eye contact. Massively parallel sequencing (MPS) of a custom-designed gene panel for epilepsy and epileptic encephalopathy containing 112 epilepsy-related genes was performed. Sanger sequencing was used to confirm the novel variants. For confirmation of the functional consequence of an intronic CDKL5 variant in patient 2, an RNA study was done. DNA sequencing revealed de novo variants in CDKL5, a c.2578C>T (p. Gln860*) present in a hemizygous state in a 3-year-old boy, and a potential splice site variant c.463+5G>A in heterozygous state in a 5-year-old girl. Multiple in silico splicing algorithms predicted a highly reduced splice site score for c.463+5G>A. A subsequent mRNA study confirmed an aberrant shorter transcript lacking exon 7. Our data confirmed that variants in the CDKL5 are associated with EIEE2. There is credible evidence that the novel identified variants are pathogenic and, therefore, are likely the cause of the disease in the presented patients. In one of the patients a stop codon variant is predicted to produce a truncated protein, and in the other patient an intronic variant results in aberrant splicing.

A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

PubMed Central

McKee, P J; Blacklaw, J; Forrest, G; Gillham, R A; Walker, S M; Connelly, D; Brodie, M J

1994-01-01

1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P < 0.05). 5. No other differences in AUCs or elimination half-lives for OHCZ were found between treated and untreated patients following single or multiple OXC dosing. 6. Median AUCs of CBZ, VPA and PHT during a dosage interval did not differ significantly after treatment with OXC and placebo. 7. Ten patients completing the study complained of side-effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction. PMID:8148215

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

PubMed Central

Carter, Dawn S.; Harrison, Anne J.; Falenski, Katherine W.; Blair, Robert E.; DeLorenzo, Robert J.

2010-01-01

Summary Acquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca2+ homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca2+ homeostasis is the neuronal calcium binding protein, calbindin-D28k that serves to buffer and transport Ca2+ ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and lasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca2+ homeostasis associated with AE. PMID:18394865

Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function?

PubMed

Avanzini, Giuliano; Depaulis, Antoine; Tassinari, Alberto; de Curtis, Marco

2013-11-01

Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions: The possibility of seizure-dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission. The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause-effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process. The results of EE studies challenge the idea of a common seizure-dependent mechanism for epilepsy progression/intellectual deterioration. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

"Epileptosis"--a syndrome or useless speculation?

PubMed

Faber, J; Vladyka, V; Dufková, D; Faltus, F; Jirák, R; Pavlovský, P; Smídová, E; Zvolský, P; Zukov, I; Klár, I; Posmurová, M; Srutová, L

1996-01-01

102 patients were divided into 3 groups: epileptics, psychotics and epileptics with psychotic symptoms. All had long been monitored for a number of clinical and laboratory parameters. Though different in many respects, all share states of sudden dysphoria, cacophoria, panic anxiety, horror, and EEG (stereo-EEG, too) signs of epileptic or other gross anomalies, often correlated to those affective disorders. Attacks of dysphoria, epilepsy, and psychosis come spontaneously and in response to biological (hypoglycemia, sleep deprivation, alcohol, menses) or psychosocial stimulation (agitation, quarrels, fear of redundancy, psychic trauma). These states (attacks, dysphoria, "neurotic" or even psychotic episodes) often provoke one another. -Calling this syndrome epileptosis, we believe its mechanism is due to lesions of the limbic and brainstem modulation systems. At the start of the process there is an epileptic focus in the amygdalo-hippocampal complex (AHC) which in itself can trigger simple or complex partial paroxysm but also-by means of electric stimulation of the AHC-states of dysphoria, anxiety, and psychotic hallucinations. Besides, a form of pathological learning develops in premorbid "hypersensitive" personality which can be put down to associative learning and to Overton's phenomenon of "state-dependent retention of learned responses". This may give rise to mutual stimulation where epileptic focal activity in AHC can provoke dysphoria while an external psychosocial situation can trigger epileptic activity there, too (AHC). Since there need not always be mydriasis (though other vegetative signs such as tachycardia, tachypnoea, nausea, blush and others are frequent) or unconsciousness, and some psychomotor manifestations may be out of the ordinary, and scalp EEG may be normal, such patients are often regarded as "hysterics" or malingerers.

Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures.

PubMed

Töllner, Kathrin; Twele, Friederike; Löscher, Wolfgang

2016-04-01

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Mutations in Prickle Orthologs Cause Seizures in Flies, Mice, and Humans

PubMed Central

Tao, Hirotaka; Manak, J. Robert; Sowers, Levi; Mei, Xue; Kiyonari, Hiroshi; Abe, Takaya; Dahdaleh, Nader S.; Yang, Tian; Wu, Shu; Chen, Shan; Fox, Mark H.; Gurnett, Christina; Montine, Thomas; Bird, Thomas; Shaffer, Lisa G.; Rosenfeld, Jill A.; McConnell, Juliann; Madan-Khetarpal, Suneeta; Berry-Kravis, Elizabeth; Griesbach, Hilary; Saneto, Russell P.; Scott, Matthew P.; Antic, Dragana; Reed, Jordan; Boland, Riley; Ehaideb, Salleh N.; El-Shanti, Hatem; Mahajan, Vinit B.; Ferguson, Polly J.; Axelrod, Jeffrey D.; Lehesjoki, Anna-Elina; Fritzsch, Bernd; Slusarski, Diane C.; Wemmie, John; Ueno, Naoto; Bassuk, Alexander G.

2011-01-01

Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution. PMID:21276947

Physiological bases of the K+ and the glutamate/GABA hypotheses of epilepsy

PubMed Central

DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

2016-01-01

Epilepsy is a heterogeneous family of neurological disorders that manifest as seizures, i.e. the hypersynchronous activity of large population of neurons. About 30% of epileptic patients do not respond to currently available antiepileptic drugs. Decades of intense research have elucidated the involvement of a number of possible signaling pathways, however, at present we do not have a fundamental understanding of epileptogenesis. In this paper, we review the literature on epilepsy under a wide-angle perspective, a mandatory choice that responds to the recurrent and unanswered question about what is epiphenomenal and what is causal to the disease. While focusing on the involvement of K+ and glutamate/GABA in determining neuronal hyperexcitability, emphasis is given to astrocytic contribution to epileptogenesis, and especially to loss-of-function of astrocytic glutamine synthetase following reactive astrogliosis, a hallmark of epileptic syndromes. We finally introduce the potential involvement of abnormal glycogen synthesis induced by excess glutamate in increasing susceptibility to seizures. PMID:24818957

Chaos Control of Epileptiform Bursting in the Brain

NASA Astrophysics Data System (ADS)

Slutzky, M. W.; Cvitanovic, P.; Mogul, D. J.

Epilepsy, defined as recurrent seizures, is a pathological state of the brain that afflicts over one percent of the world's population. Seizures occur as populations of neurons in the brain become overly synchronized. Although pharmacological agents are the primary treatment for preventing or reducing the incidence of these seizures, over 30% of epilepsy cases are not adequately helped by standard medical therapies. Several groups are exploring the use of electrical stimulation to terminate or prevent epileptic seizures. One experimental model used to test these algorithms is the brain slice where a select region of the brain is cut and kept viable in a well-oxygenated artificial cerebrospinal fluid. Under certain conditions, such slices may be made to spontaneously and repetitively burst, thereby providing an in vitro model of epilepsy. In this chapter, we discuss our efforts at applying chaos analysis and chaos control algorithms for manipulating this seizure-like behavior in a brain slice model. These techniques may provide a nonlinear control pathway for terminating or potentially preventing epileptic seizures in the whole brain.

Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients

PubMed Central

Tartara, A.; Galimberti, C.A.; Manni, R.; Parietti, L.; Zucca, C.; Baasch, H.; Caresia, L.; Mück, W.; Barzaghi, N.; Gatti, G.; Perucca, E.

1991-01-01

1 The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2 Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P < 0.01) in patients taking enzyme-inducing anticonvulsants and increased by about 50% (P < 0.05) in patients taking sodium valproate. 3 Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 ± 2.0 h vs 9.1 ± 3.4 h, means ± s.d., P < 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 ± 1.8 h) were similar to those found in controls. PMID:1777370

Extracellular metabolites in the cortex and hippocampus of epileptic patients.

PubMed

Cavus, Idil; Kasoff, Willard S; Cassaday, Michael P; Jacob, Ralph; Gueorguieva, Ralitza; Sherwin, Robert S; Krystal, John H; Spencer, Dennis D; Abi-Saab, Walid M

2005-02-01

Interictal brain energy metabolism and glutamate-glutamine cycling are impaired in epilepsy and may contribute to seizure generation. We used the zero-flow microdialysis method to measure the extracellular levels of glutamate, glutamine, and the major energy substrates glucose and lactate in the epileptogenic and the nonepileptogenic cortex and hippocampus of 38 awake epileptic patients during the interictal period. Depth electrodes attached to microdialysis probes were used to identify the epileptogenic and the nonepileptogenic sites. The epileptogenic hippocampus had surprisingly high basal glutamate levels, low glutamine/glutamate ratio, high lactate levels, and indication for poor glucose utilization. The epileptogenic cortex had only marginally increased glutamate levels. We propose that interictal energetic deficiency in the epileptogenic hippocampus could contribute to impaired glutamate reuptake and glutamate-glutamine cycling, resulting in persistently increased extracellular glutamate, glial and neuronal toxicity, increased lactate production together with poor lactate and glucose utilization, and ultimately worsening energy metabolism. Our data suggest that a different neurometabolic process underlies the neocortical epilepsies.

LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.

PubMed

Stowe, Robert C; Sun, Qin; Elsea, Sarah H; Scaglia, Fernando

2018-05-01

Lipoic acid is an essential cofactor for the mitochondrial 2-ketoacid dehydrogenase complexes and the glycine cleavage system. Lipoyltransferase 1 catalyzes the covalent attachment of lipoate to these enzyme systems. Pathogenic variants in LIPT1 gene have recently been described in four patients from three families, commonly presenting with severe lactic acidosis resulting in neonatal death and/or poor neurocognitive outcomes. We report a 2-month-old male with severe lactic acidosis, refractory status epilepticus, and brain imaging suggestive of Leigh disease. Exome sequencing implicated compound heterozygous LIPT1 pathogenic variants. We describe the fifth case of LIPT1 deficiency, whose phenotype progressed to that of an early infantile epileptic encephalopathy, which is novel compared to previously described patients whom we will review. Due to the significant biochemical and phenotypic overlap that LIPT1 deficiency and mitochondrial energy cofactor disorders have with pyruvate dehydrogenase deficiency and/or nonketotic hyperglycinemia, they are and have been presumptively under-diagnosed without exome sequencing. © 2018 Wiley Periodicals, Inc.

A Phenomenological Synapse Model for Asynchronous Neurotransmitter Release

PubMed Central

Wang, Tao; Yin, Luping; Zou, Xiaolong; Shu, Yousheng; Rasch, Malte J.; Wu, Si

2016-01-01

Neurons communicate with each other via synapses. Action potentials cause release of neurotransmitters at the axon terminal. Typically, this neurotransmitter release is tightly time-locked to the arrival of an action potential and is thus called synchronous release. However, neurotransmitter release is stochastic and the rate of release of small quanta of neurotransmitters can be considerably elevated even long after the ceasing of spiking activity, leading to asynchronous release of neurotransmitters. Such asynchronous release varies for tissue and neuron types and has been shown recently to be pronounced in fast-spiking neurons. Notably, it was found that asynchronous release is enhanced in human epileptic tissue implicating a possibly important role in generating abnormal neural activity. Current neural network models for simulating and studying neural activity virtually only consider synchronous release and ignore asynchronous transmitter release. Here, we develop a phenomenological model for asynchronous neurotransmitter release, which, on one hand, captures the fundamental features of the asynchronous release process, and, on the other hand, is simple enough to be incorporated in large-size network simulations. Our proposed model is based on the well-known equations for short-term dynamical synaptic interactions and includes an additional stochastic term for modeling asynchronous release. We use experimental data obtained from inhibitory fast-spiking synapses of human epileptic tissue to fit the model parameters, and demonstrate that our model reproduces the characteristics of realistic asynchronous transmitter release. PMID:26834617

Emperor Napoleon Bonaparte: did he have seizures? Psychogenic or epileptic or both?

PubMed

Hughes, John R

2003-12-01

Napoleon Bonaparte was a general in the French army at 24 years of age, later conquering most of Europe. He was one of the greatest military geniuses the world has ever known, but also an extremely intelligent individual. Did he have seizures? The evidence shows that he had both psychogenic and epileptic attacks. The psychogenic attacks were likely related to the tremendous stress in his life, and the epileptic seizures were the result of chronic uremia from a severe urethral stricture caused by gonorrhea that was transmitted from his wife, Empress Josephine.

Anesthesia-induced epilepsy: causes and treatment.

PubMed

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.

Effects of anticonvulsants and inactivity on bone disease in epileptics

PubMed Central

Murchison, Lilian E.; Bewsher, P. D.; Chesters, Marion; Gilbert, J.; Catto, G.; Law, Elizabeth; McKay, E.; Ross, H. S.

1975-01-01

No significant biochemical or radiological features of vitamin D deficiency were found in groups of juvenile and adult epileptics and control groups of non-epileptic patients in hospitals for the mentally retarded. There was evidence of hepatic enzyme induction in patients on anticonvulsants, in that urinary D-glucaric acid concentration and excretion were raised. No effect was found of prolonged anticonvulsant therapy on bone densitometry, but in children immobility was closely associated with decreased bone density. The evidence suggests that disuse osteoporosis is the major bone disease in these mentally retarded children. PMID:1161672

EEG analysis using wavelet-based information tools.

PubMed

Rosso, O A; Martin, M T; Figliola, A; Keller, K; Plastino, A

2006-06-15

Wavelet-based informational tools for quantitative electroencephalogram (EEG) record analysis are reviewed. Relative wavelet energies, wavelet entropies and wavelet statistical complexities are used in the characterization of scalp EEG records corresponding to secondary generalized tonic-clonic epileptic seizures. In particular, we show that the epileptic recruitment rhythm observed during seizure development is well described in terms of the relative wavelet energies. In addition, during the concomitant time-period the entropy diminishes while complexity grows. This is construed as evidence supporting the conjecture that an epileptic focus, for this kind of seizures, triggers a self-organized brain state characterized by both order and maximal complexity.

Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

PubMed

Mathew, Jobin; Gangadharan, Gireesh; Kuruvilla, Korah P; Paulose, C S

2011-01-01

In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά₁), GABA(Aά₅) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

Epileptic seizure detection from EEG signals with phase-amplitude cross-frequency coupling and support vector machine

NASA Astrophysics Data System (ADS)

Liu, Yang; Wang, Jiang; Cai, Lihui; Chen, Yingyuan; Qin, Yingmei

2018-03-01

As a pattern of cross-frequency coupling (CFC), phase-amplitude coupling (PAC) depicts the interaction between the phase and amplitude of distinct frequency bands from the same signal, and has been proved to be closely related to the brain’s cognitive and memory activities. This work utilized PAC and support vector machine (SVM) classifier to identify the epileptic seizures from electroencephalogram (EEG) data. The entropy-based modulation index (MI) matrixes are used to express the strength of PAC, from which we extracted features as the input for classifier. Based on the Bonn database, which contains five datasets of EEG segments obtained from healthy volunteers and epileptic subjects, a 100% classification accuracy is achieved for identifying seizure ictal from healthy data, and an accuracy of 97.67% is reached in the classification of ictal EEG signals from inter-ictal EEGs. Based on the CHB-MIT database which is a group of continuously recorded epileptic EEGs by scalp electrodes, a 97.50% classification accuracy is obtained and a raising sign of MI value is found at 6s before seizure onset. The classification performance in this work is effective, and PAC can be considered as a useful tool for detecting and predicting the epileptic seizures and providing reference for clinical diagnosis.

Measurement of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid in the cerebrospinal fluid of children.

PubMed

Akiyama, Tomoyuki; Akiyama, Mari; Hayashi, Yumiko; Shibata, Takashi; Hanaoka, Yoshiyuki; Toda, Soichiro; Imai, Katsumi; Hamano, Shin-Ichiro; Okanishi, Tohru; Yoshinaga, Harumi; Kobayashi, Katsuhiro

2017-03-01

We quantified pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) in the cerebrospinal fluid (CSF) of children and to investigate the effect of age, sex, epilepsy, and anti-epileptic drug (AED) therapy on these vitamers. CSF samples prospectively collected from 116 pediatric patients were analyzed. PLP, PL, and PA were measured using high-performance liquid chromatography with fluorescence detection, using pre-column derivatization by semicarbazide. Effects of age, sex, epilepsy, and AEDs on these vitamers and the PLP/PL ratio were evaluated using multiple linear regression models. The PLP, PL, and PA concentrations were correlated negatively with age and the PLP/PL ratio was correlated positively with age. Multiple regression analysis revealed that the presence of epilepsy was associated with lower PLP concentrations and PLP/PL ratios but sex and AED therapy had no influence on these values. The observed ranges of these vitamers in epileptic and non-epileptic patients were demonstrated. We showed the age dependence of PLP and PL in CSF from pediatric patients. Epileptic patients had lower PLP concentrations and PLP/PL ratios than non-epileptic patients, but it is unknown whether this is the cause, or a result, of epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

PubMed

Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

2011-11-01

Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), was negative. The patient showed a partial response to steroid treatment, which was started late in the disease course. On review at 13 months of age, her development was consistent with an age of 5 to 6 months. These results suggest that VGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Epileptic Seizure Detection Based on Time-Frequency Images of EEG Signals using Gaussian Mixture Model and Gray Level Co-Occurrence Matrix Features.

PubMed

Li, Yang; Cui, Weigang; Luo, Meilin; Li, Ke; Wang, Lina

2018-01-25

The electroencephalogram (EEG) signal analysis is a valuable tool in the evaluation of neurological disorders, which is commonly used for the diagnosis of epileptic seizures. This paper presents a novel automatic EEG signal classification method for epileptic seizure detection. The proposed method first employs a continuous wavelet transform (CWT) method for obtaining the time-frequency images (TFI) of EEG signals. The processed EEG signals are then decomposed into five sub-band frequency components of clinical interest since these sub-band frequency components indicate much better discriminative characteristics. Both Gaussian Mixture Model (GMM) features and Gray Level Co-occurrence Matrix (GLCM) descriptors are then extracted from these sub-band TFI. Additionally, in order to improve classification accuracy, a compact feature selection method by combining the ReliefF and the support vector machine-based recursive feature elimination (RFE-SVM) algorithm is adopted to select the most discriminative feature subset, which is an input to the SVM with the radial basis function (RBF) for classifying epileptic seizure EEG signals. The experimental results from a publicly available benchmark database demonstrate that the proposed approach provides better classification accuracy than the recently proposed methods in the literature, indicating the effectiveness of the proposed method in the detection of epileptic seizures.

Treatment of Focal Status Epilepticus plus Epileptic Spasms with Leukotomy in an Infant with TSC 1 Mutation: A Case Study.

PubMed

Park, Jun T; Shahid, Asim M; Miller, Jonathan P; Lüders, Hans O

2015-12-01

Focal status epilepticus and catastrophic epilepsy are not rare in infants. Epilepsy surgery can be safely done in selected infants to cure epilepsy. We report on an infant who began having drug-resistant status epilepticus at 2 weeks of age and developed epileptic spasms. We discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives. Presurgical evaluation consisted of 32-channel scalp video EEG using the standard 10-20 system of electrodes, 3-Tesla brain magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. The surgery consisted of resection of the extensive epileptogenic lesion, in addition to disconnection of the left frontal lobe anterior to the motor strip. The infant underwent epilepsy surgery at three months of age. At two-year follow up, she remained seizure free, with no focal motor deficit and the epileptic encephalopathy resolved. The disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue. We highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy. In the process, we demonstrate how epileptic spasms, although clinically and electrographically generalized, resolved after disconnecting the epileptogenic zone.

eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures.

PubMed

Heise, Christopher; Taha, Elham; Murru, Luca; Ponzoni, Luisa; Cattaneo, Angela; Guarnieri, Fabrizia C; Montani, Caterina; Mossa, Adele; Vezzoli, Elena; Ippolito, Giulio; Zapata, Jonathan; Barrera, Iliana; Ryazanov, Alexey G; Cook, James; Poe, Michael; Stephen, Michael Rajesh; Kopanitsa, Maksym; Benfante, Roberta; Rusconi, Francesco; Braida, Daniela; Francolini, Maura; Proud, Christopher G; Valtorta, Flavia; Passafaro, Maria; Sala, Mariaelvina; Bachi, Angela; Verpelli, Chiara; Rosenblum, Kobi; Sala, Carlo

2017-03-01

Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effects of the synthetic cannabinoid receptor agonists, WIN55,212-2 and CP55,940, on salicylate-induced tinnitus in rats.

PubMed

Zheng, Yiwen; Stiles, Lucy; Hamilton, Emma; Smith, Paul F; Darlington, Cynthia L

2010-09-01

Previous studies in animals and humans have shown that, in some cases at least, anti-epileptic drugs can reduce the severity of tinnitus. Given that cannabinoid receptor agonists have been shown to exert anti-epileptic effects in some circumstances, we investigated whether two synthetic CB(1)/CB(2) receptor agonists, WIN55,212-2, and CP55,940, could inhibit the behavioural manifestations of salicylate-induced tinnitus in rats in a conditioned suppression task. We found that neither WIN55,212-2 (3.0 mg/kg s.c) nor CP55,940 (0.1 or 0.3 mg/kg s.c), significantly reduced conditioned behaviour associated with tinnitus. However, both 3 mg/kg WIN55,212-2 and 0.3 mg/kg CP55,940 did significantly increase tinnitus-related behaviour compared to the vehicle control groups. These results suggest that cannabinoid receptor agonists may not be useful in the treatment of salicylate-induced tinnitus and that at certain doses, they could actually exacerbate the condition. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Optogenetic stimulation of a meso-scale human cortical model

NASA Astrophysics Data System (ADS)

Selvaraj, Prashanth; Szeri, Andrew; Sleigh, Jamie; Kirsch, Heidi

2015-03-01

Neurological phenomena like sleep and seizures depend not only on the activity of individual neurons, but on the dynamics of neuron populations as well. Meso-scale models of cortical activity provide a means to study neural dynamics at the level of neuron populations. Additionally, they offer a safe and economical way to test the effects and efficacy of stimulation techniques on the dynamics of the cortex. Here, we use a physiologically relevant meso-scale model of the cortex to study the hypersynchronous activity of neuron populations during epileptic seizures. The model consists of a set of stochastic, highly non-linear partial differential equations. Next, we use optogenetic stimulation to control seizures in a hyperexcited cortex, and to induce seizures in a normally functioning cortex. The high spatial and temporal resolution this method offers makes a strong case for the use of optogenetics in treating meso scale cortical disorders such as epileptic seizures. We use bifurcation analysis to investigate the effect of optogenetic stimulation in the meso scale model, and its efficacy in suppressing the non-linear dynamics of seizures.

All together now: Analogies between chimera state collapses and epileptic seizures

NASA Astrophysics Data System (ADS)

Andrzejak, Ralph G.; Rummel, Christian; Mormann, Florian; Schindler, Kaspar

2016-03-01

Conceptually and structurally simple mathematical models of coupled oscillator networks can show a rich variety of complex dynamics, providing fundamental insights into many real-world phenomena. A recent and not yet fully understood example is the collapse of coexisting synchronous and asynchronous oscillations into a globally synchronous motion found in networks of identical oscillators. Here we show that this sudden collapse is promoted by a further decrease of synchronization, rather than by critically high synchronization. This strikingly counterintuitive mechanism can be found also in nature, as we demonstrate on epileptic seizures in humans. Analyzing spatiotemporal correlation profiles derived from intracranial electroencephalographic recordings (EEG) of seizures in epilepsy patients, we found a pronounced decrease of correlation at the seizure onsets. Applying our findings in a closed-loop control scheme to models of coupled oscillators in chimera states, we succeed in both provoking and preventing outbreaks of global synchronization. Our findings not only advance the understanding of networks of coupled dynamics but can open new ways to control them, thus offering a vast range of potential new applications.

Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms.

PubMed

Hussain, Shaun A; Shin, Ji Hyun; Shih, Evan J; Murata, Kristina K; Sewak, Sarika; Kezele, Michele E; Sankar, Raman; Matsumoto, Joyce H

2016-02-01

Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12-months of ketogenic diet exposure. Adverse events were similarly ascertained. We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Recording temporal lobe epileptic activity with MEG in a light-weight magnetic shield.

PubMed

Carrette, Evelien; Op de Beeck, Marc; Bourguignon, Mathieu; Boon, Paul; Vonck, Kristl; Legros, Benjamin; Goldman, Serge; Van Bogaert, Patrick; De Tiège, Xavier

2011-06-01

To assess the interictal epileptic discharges (IEDs) detection rate of magnetoencephalography (MEG) recordings performed in a new light-weight magnetic shielding (LMSR) concept in a large group of consecutive patients with presumed mesiotemporal lobe epilepsy (MTLE). Thirty-eight patients (23 women; age range: 6-63 years) with presumed MTLE were prospectively studied. MEG investigations were performed with the 306-channel Elekta Neuromag® MEG-system installed in a normal hospital environment into a LMSR (MaxShield, Elekta Oy). Equivalent current dipoles (ECD, g/% > 80%) corresponding to epileptic events were fitted to each patient's spherical head model at IEDs onset and peak and then superimposed on the patient's co-registered MRI. IEDs were observed in 26 out of 38 patients (68.4%). Temporal ECDs were mesial in 14 patients, anterior in 23 patients and posterior in 8 patients. Interestingly, in 6 patients, ECDs fitted at spike-onset were localized in the hippocampus while at the peak of the spike, they had an anterior temporal location. MEG using LMSR provides adequate signal to noise ratio (SNR) to allow reliable detection and localization of single epileptic abnormalities on continuous MEG data in 68% of patients with presumed MTLE. Moreover, mesial temporal epileptic sources were detected in 54% of patients with abnormal MEG. The SNR of MEG data acquired using the LMSR is therefore suitable for the non-invasive localization of epileptic foci in patients with MTLE. The use of LMSR, which are cheaper and smaller than conventional MSR, should facilitate the development of MEG in clinical environments. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Using bivariate signal analysis to characterize the epileptic focus: the benefit of surrogates.

PubMed

Andrzejak, R G; Chicharro, D; Lehnertz, K; Mormann, F

2011-04-01

The disease epilepsy is related to hypersynchronous activity of networks of neurons. While acute epileptic seizures are the most extreme manifestation of this hypersynchronous activity, an elevated level of interdependence of neuronal dynamics is thought to persist also during the seizure-free interval. In multichannel recordings from brain areas involved in the epileptic process, this interdependence can be reflected in an increased linear cross correlation but also in signal properties of higher order. Bivariate time series analysis comprises a variety of approaches, each with different degrees of sensitivity and specificity for interdependencies reflected in lower- or higher-order properties of pairs of simultaneously recorded signals. Here we investigate which approach is best suited to detect putatively elevated interdependence levels in signals recorded from brain areas involved in the epileptic process. For this purpose, we use the linear cross correlation that is sensitive to lower-order signatures of interdependence, a nonlinear interdependence measure that integrates both lower- and higher-order properties, and a surrogate-corrected nonlinear interdependence measure that aims to specifically characterize higher-order properties. We analyze intracranial electroencephalographic recordings of the seizure-free interval from 29 patients with an epileptic focus located in the medial temporal lobe. Our results show that all three approaches detect higher levels of interdependence for signals recorded from the brain hemisphere containing the epileptic focus as compared to signals recorded from the opposite hemisphere. For the linear cross correlation, however, these differences are not significant. For the nonlinear interdependence measure, results are significant but only of moderate accuracy with regard to the discriminative power for the focal and nonfocal hemispheres. The highest significance and accuracy is obtained for the surrogate-corrected nonlinear interdependence measure.

Using bivariate signal analysis to characterize the epileptic focus: The benefit of surrogates

NASA Astrophysics Data System (ADS)

Andrzejak, R. G.; Chicharro, D.; Lehnertz, K.; Mormann, F.

2011-04-01

The disease epilepsy is related to hypersynchronous activity of networks of neurons. While acute epileptic seizures are the most extreme manifestation of this hypersynchronous activity, an elevated level of interdependence of neuronal dynamics is thought to persist also during the seizure-free interval. In multichannel recordings from brain areas involved in the epileptic process, this interdependence can be reflected in an increased linear cross correlation but also in signal properties of higher order. Bivariate time series analysis comprises a variety of approaches, each with different degrees of sensitivity and specificity for interdependencies reflected in lower- or higher-order properties of pairs of simultaneously recorded signals. Here we investigate which approach is best suited to detect putatively elevated interdependence levels in signals recorded from brain areas involved in the epileptic process. For this purpose, we use the linear cross correlation that is sensitive to lower-order signatures of interdependence, a nonlinear interdependence measure that integrates both lower- and higher-order properties, and a surrogate-corrected nonlinear interdependence measure that aims to specifically characterize higher-order properties. We analyze intracranial electroencephalographic recordings of the seizure-free interval from 29 patients with an epileptic focus located in the medial temporal lobe. Our results show that all three approaches detect higher levels of interdependence for signals recorded from the brain hemisphere containing the epileptic focus as compared to signals recorded from the opposite hemisphere. For the linear cross correlation, however, these differences are not significant. For the nonlinear interdependence measure, results are significant but only of moderate accuracy with regard to the discriminative power for the focal and nonfocal hemispheres. The highest significance and accuracy is obtained for the surrogate-corrected nonlinear interdependence measure.

Study on the Relationships between Intrinsic Functional Connectivity of the Default Mode Network and Transient Epileptic Activity.

PubMed

Lopes, Renaud; Moeller, Friederike; Besson, Pierre; Ogez, François; Szurhaj, William; Leclerc, Xavier; Siniatchkin, Michael; Chipaux, Mathilde; Derambure, Philippe; Tyvaert, Louise

2014-01-01

Simultaneous recording of electroencephalogram and functional MRI (EEG-fMRI) is a powerful tool for localizing epileptic networks via the detection of hemodynamic changes correlated with interictal epileptic discharges (IEDs). fMRI can be used to study the long-lasting effect of epileptic activity by assessing stationary functional connectivity during the resting-state period [especially, the connectivity of the default mode network (DMN)]. Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) are associated with low responsiveness and disruption of DMN activity. A dynamic functional connectivity approach might enable us to determine the effect of IEDs on DMN connectivity and to better understand the correlation between DMN connectivity changes and altered consciousness. We studied dynamic changes in DMN intrinsic connectivity and their relation to IEDs. Six IGE patients (with generalized spike and slow-waves) and 6 TLE patients (with unilateral left temporal spikes) were included. Functional connectivity before, during, and after IEDs was estimated using a sliding window approach and compared with the baseline period. No dependence on window size was observed. The baseline DMN connectivity was decreased in the left hemisphere (ipsilateral to the epileptic focus) in TLEs and was less strong but remained bilateral in IGEs. We observed an overall increase in DMN intrinsic connectivity prior to the onset of IEDs in both IGEs and TLEs. After IEDs in TLEs, we found that DMN connectivity increased before it returned to baseline values. Most of the DMN regions with increased connectivity before and after IEDs were lateralized to the left hemisphere in TLE (i.e., ipsilateral to the epileptic focus). RESULTS suggest that DMN connectivity may facilitate IED generation and may be affected at the time of the IED. However, these results need to be confirmed in a larger independent cohort.

Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience

PubMed Central

Zeka, Naim; Gërguri, Abdurrahim; Bejiqi, Ramush; Retkoceri, Ragip; Vuciterna, Armend

2017-01-01

BACKGROUND: West Syndrome (WS) represents as a specific epileptic encephalopathy characterised with a unique type of attacks, called infantile spasms, severe forms of abnormalities in electroencephalographic (EEG) records as a hypsarythmias and delays in the psychomotoric development. The characteristics of the disease, mostly affecting male gender, are infantile spasms and typical findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many factors in the undeveloped brain. AIM: We aimed: (1) to see the incidence of the illness and the spreading out because of gender in rapport with other syndromes in the epileptic encephalopathies group; (2) to show principles of the treatment for the illness; and (3) to present the effects of the disease in the psycho-motoric development of affected children. METHODS: The study was designed as a cross-sectional study of the patients with epileptic encephalopathies, treated in Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of December 2015. RESULTS: From the cohort group of 97 children diagnosed with epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were noted. The earliest age of disease manifestation was 74 days (± 63.8 days). On the group of children with WS, 13 of them with Natrium Valpropat were treated, with the doses of 301.9 mg (± 64.1). From the cohort group, in 89 children (91.8%) psychomotoric retardation was documented, within the higher reoccurrence in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%). CONCLUSION: WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome. PMID:29362620

Modeling of intracerebral interictal epileptic discharges: Evidence for network interactions.

PubMed

Meesters, Stephan; Ossenblok, Pauly; Colon, Albert; Wagner, Louis; Schijns, Olaf; Boon, Paul; Florack, Luc; Fuster, Andrea

2018-06-01

The interictal epileptic discharges (IEDs) occurring in stereotactic EEG (SEEG) recordings are in general abundant compared to ictal discharges, but difficult to interpret due to complex underlying network interactions. A framework is developed to model these network interactions. To identify the synchronized neuronal activity underlying the IEDs, the variation in correlation over time of the SEEG signals is related to the occurrence of IEDs using the general linear model. The interdependency is assessed of the brain areas that reflect highly synchronized neural activity by applying independent component analysis, followed by cluster analysis of the spatial distributions of the independent components. The spatiotemporal interactions of the spike clusters reveal the leading or lagging of brain areas. The analysis framework was evaluated for five successfully operated patients, showing that the spike cluster that was related to the MRI-visible brain lesions coincided with the seizure onset zone. The additional value of the framework was demonstrated for two more patients, who were MRI-negative and for whom surgery was not successful. A network approach is promising in case of complex epilepsies. Analysis of IEDs is considered a valuable addition to routine review of SEEG recordings, with the potential to increase the success rate of epilepsy surgery. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Specific binding of lacosamide to collapsin response mediator protein 2 (CRMP2) and direct impairment of its canonical function: implications for the therapeutic potential of lacosamide

PubMed Central

Wilson, Sarah M.; Khanna, Rajesh

2014-01-01

The novel anti-epileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide’s ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e. seizures). While the role of CRMP2 in epilepsy has not been well-studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease-modifying. Recently, however, the validity of lacosamide’s interaction with CRMP2 has come under scrutiny. In this review, we address the contradictory reports concerning the binding of lacosamide to CRMP2, as well as, the ability of lacosamide to directly impact CRMP2 function. Additionally, we address similarly contradicting reports regarding the potential disease-modifying effect of lacosamide on the development and progression of epilepsy. As the vast majority of anti-epileptic drugs influence only the symptoms of epilepsy, the ability to hinder disease progression would be a major breakthrough in efforts to cure or prevent this debilitating syndrome. PMID:24944082

Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions

PubMed Central

Laufs, Helmut; Hamandi, Khalid; Salek-Haddadi, Afraim; Kleinschmidt, Andreas K; Duncan, John S; Lemieux, Louis

2007-01-01

A cerebral network comprising precuneus, medial frontal, and temporoparietal cortices is less active both during goal-directed behavior and states of reduced consciousness than during conscious rest. We tested the hypothesis that the interictal epileptic discharges affect activity in these brain regions in patients with temporal lobe epilepsy who have complex partial seizures. At the group level, using electroencephalography-correlated functional magnetic resonance imaging in 19 consecutive patients with focal epilepsy, we found common decreases of resting state activity in 9 patients with temporal lobe epilepsy (TLE) but not in 10 patients with extra-TLE. We infer that the functional consequences of TLE interictal epileptic discharges are different from those in extra-TLE and affect ongoing brain function. Activity increases were detected in the ipsilateral hippocampus in patients with TLE, and in subthalamic, bilateral superior temporal and medial frontal brain regions in patients with extra-TLE, possibly indicating effects of different interictal epileptic discharge propagation. PMID:17133385

CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients.

PubMed

Jähn, Johanna; Caliebe, Almuth; von Spiczak, Sarah; Boor, Rainer; Stefanova, Irina; Stephani, Ulrich; Helbig, Ingo; Muhle, Hiltrud

2013-07-01

CDKL5 mutations cause severe epilepsy in infancy with subsequent epileptic encephalopathy. As yet, few studies report on long-term observations in patients with CDKL5-related epileptic encephalopathy. In this study, we describe the evolution of the epilepsy phenotype and the electroencephalographic (EEG) features in 4 patients during a maximum observation period of 22 years. All 4 patients had epilepsy starting with focal seizures in the first 3 months of life, evolving to epileptic spasms between the ages of 2 and 6 years and later on to tonic seizures. In 3 patients, epilepsy was resistant to antiepileptic therapy. Although there was no common EEG pattern in all patients, late hypsarrhythmia until the age of 9 years was observed in 2 patients. CDKL5-related epileptic encephalopathies are a group of refractory seizure disorders starting in early infancy. The phenomenon of late hypsarrhythmia may help define a subgroup of patients with severe and adverse outcomes.

Epilepsy phenotypes in siblings with Norrie disease.

PubMed

Okumura, Akihisa; Arai, Eisuke; Kitamura, Yuri; Abe, Shinpei; Ikeno, Mitsuru; Fujimaki, Takuro; Yamamoto, Toshiyuki; Shimizu, Toshiaki

2015-11-01

Norrie disease is an X-linked recessive disorder that is characterized by congenital blindness. Although epileptic seizures are observed in some patients with Norrie disease, little is known about this phenomenon. Here, we report the manifestation of epilepsy in siblings with Norrie disease to increase our knowledge of epilepsy in this condition. Three brothers with congenital blindness were diagnosed with Norrie disease after genetic analyses indicated the deletion of exon 2 of the NDP gene. The eldest brother had suffered from epileptic seizures since the age of 11years, and his seizures were resistant to antiepileptic drugs. Although the second brother had no epileptic seizures, the youngest sibling had experiences epileptic seizures since the age of 8years. His seizures were controlled using lamotrigine and levetiracetam. An electroencephalography (EEG) revealed epileptiform discharges in the occipital areas in all three brothers. A study of these patients will increase our knowledge of epilepsy in patients with Norrie disease. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Classifying epileptic EEG signals with delay permutation entropy and Multi-Scale K-means.

PubMed

Zhu, Guohun; Li, Yan; Wen, Peng Paul; Wang, Shuaifang

2015-01-01

Most epileptic EEG classification algorithms are supervised and require large training datasets, that hinder their use in real time applications. This chapter proposes an unsupervised Multi-Scale K-means (MSK-means) MSK-means algorithm to distinguish epileptic EEG signals and identify epileptic zones. The random initialization of the K-means algorithm can lead to wrong clusters. Based on the characteristics of EEGs, the MSK-means MSK-means algorithm initializes the coarse-scale centroid of a cluster with a suitable scale factor. In this chapter, the MSK-means algorithm is proved theoretically superior to the K-means algorithm on efficiency. In addition, three classifiers: the K-means, MSK-means MSK-means and support vector machine (SVM), are used to identify seizure and localize epileptogenic zone using delay permutation entropy features. The experimental results demonstrate that identifying seizure with the MSK-means algorithm and delay permutation entropy achieves 4. 7 % higher accuracy than that of K-means, and 0. 7 % higher accuracy than that of the SVM.

[Portable Epileptic Seizure Monitoring Intelligent System Based on Android System].

PubMed

Liang, Zhenhu; Wu, Shufeng; Yang, Chunlin; Jiang, Zhenzhou; Yu, Tao; Lu, Chengbiao; Li, Xiaoli

2016-02-01

The clinical electroencephalogram (EEG) monitoring systems based on personal computer system can not meet the requirements of portability and home usage. The epilepsy patients have to be monitored in hospital for an extended period of time, which imposes a heavy burden on hospitals. In the present study, we designed a portable 16-lead networked monitoring system based on the Android smart phone. The system uses some technologies including the active electrode, the WiFi wireless transmission, the multi-scale permutation entropy (MPE) algorithm, the back-propagation (BP) neural network algorithm, etc. Moreover, the software of Android mobile application can realize the processing and analysis of EEG data, the display of EEG waveform and the alarm of epileptic seizure. The system has been tested on the mobile phones with Android 2. 3 operating system or higher version and the results showed that this software ran accurately and steadily in the detection of epileptic seizure. In conclusion, this paper provides a portable and reliable solution for epileptic seizure monitoring in clinical and home applications.

Ketogenic diet efficacy in the treatment of intractable epileptic spasms.

PubMed

Kayyali, Husam R; Gustafson, Megan; Myers, Tara; Thompson, Lindsey; Williams, Michelle; Abdelmoity, Ahmad

2014-03-01

To determine the efficacy of the ketogenic diet in controlling epileptic spasms after failing traditional antiepileptic medication therapy. This is a prospective, case-based study of all infants with epileptic spasms who were referred for treatment with the ketogenic diet at our hospital between 2009 and 2012. All subjects continued to have epileptic spasms with evidence of hypsarrhythmia or severe epileptic encephalopathy on electroencephalography despite appropriate medication treatments. The diet efficacy was assessed through clinic visits, phone communications, and electroencephalography. Quality of life improvement was charted based on the caregiver's perspective. Twenty infants (15 males) were included in the study. The mean age at seizure onset was 4.5 months. Age at ketogenic diet initiation was 0.3 to 2.9 years (mean 1.20, standard deviation 0.78). Fifteen patients had epileptic spasms of unknown etiology; three had perinatal hypoxic ischemic encephalopathy, one had lissencephaly, and one had STXBP1 mutation. Fifteen infants failed to respond to adrenocorticotropin hormone and/or vigabatrin before going on the ketogenic diet. Three months after starting the diet, >50% seizure reduction was achieved in 70% of patients (95% CI 48-86). These results were maintained at 6- and 12-month intervals. All eight of the patients followed for 24 months had >50% seizure reduction (95% CI 63-100). At least 90% seizure reduction was reported in 20% of patients at 3 months (95% CI 7-42), 22% (95% CI 8-46) at 6 months, and 35% (95% CI 17-59) at 12 months. The majority of patients (63%) achieved improvement of their spasms within 1 month after starting the diet. Sixty percent of patients had electroencephalographic improvement. All caregivers reported improvement of the quality of life at the 3-month visit (95% confidence interval 81-100). This ratio was 94% at 6 months (95% CI 72-99) and 82% at 12 months (95% CI 58-95). The ketogenic diet is a safe and potentially effective method of treatment for patients with epileptic spasms, especially those who do not respond to customary medication therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

Cross-sectional study of the hospital management of adult patients with a suspected seizure (EPIC2)

PubMed Central

Dickson, Jon Mark; Dudhill, Hannah; Shewan, Jane; Mason, Sue; Grünewald, Richard A; Reuber, Markus

2017-01-01

Objective To determine the clinical characteristics, management and outcomes of patients taken to hospital by emergency ambulance after a suspected seizure. Design Quantitative cross-sectional retrospective study of a consecutive series of patients. Setting An acute hospital trust in a large city in England. Participants In 2012–2013, the regions’ ambulance service managed 605 481 emergency incidents, 74 141/605 481 originated from Sheffield (a large city in the region), 2121/74 141 (2.9%) were suspected seizures and 178/2121 occurred in May 2012. We undertook detailed analysis of the medical records of the 91/178 patients who were transported to the city’s acute hospital. After undertaking a retrospective review of the medical records, the best available aetiological explanation for the seizures was determined. Results The best available aetiological explanation for 74.7% (68/91) of the incidents was an epileptic seizure, 11.0% (10/91) were psychogenic non-epileptic seizures and 9.9% (9/91) were cardiogenic events. The epileptic seizures fall into the following four categories: first epileptic seizure (13.2%, 12/91), epileptic seizure with a historical diagnosis of epilepsy (30.8%, 28/91), recurrent epileptic seizures without a historical diagnosis of epilepsy (20.9%, 19/91) and acute symptomatic seizures (9.9%, 9/91). Of those with seizures (excluding cardiogenic events), 2.4% (2/82) of patients were seizing on arrival in the Emergency Department (ED), 19.5% (16/82) were postictal and 69.5% (57/82) were alert. 63.4% (52/82) were discharged at the end of their ED attendance and 36.5% (19/52) of these had no referral or follow-up. Conclusions Most suspected seizures are epileptic seizures but this is a diagnostically heterogeneous group. Only a small minority of patients require emergency medical care but most are transported to hospital. Few patients receive expert review and many are discharged home without referral to a specialist leaving them at risk of further seizures and the associated morbidity, mortality and health services costs of poorly controlled epilepsy. PMID:28706099

Uncaria rhynchophylla upregulates the expression of MIF and cyclophilin A in kainic acid-induced epilepsy rats: A proteomic analysis.

PubMed

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.

CDKL5 alterations lead to early epileptic encephalopathy in both genders.

PubMed

Liang, Jao-Shwann; Shimojima, Keiko; Takayama, Rumiko; Natsume, Jun; Shichiji, Minobu; Hirasawa, Kyoko; Imai, Kaoru; Okanishi, Tohru; Mizuno, Seiji; Okumura, Akihisa; Sugawara, Midori; Ito, Tomoshiro; Ikeda, Hiroko; Takahashi, Yukitoshi; Oguni, Hirokazu; Imai, Katsumi; Osawa, Makiko; Yamamoto, Toshiyuki

2011-10-01

Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Persistent genital arousal disorder associated with functional hyperconnectivity of an epileptic focus.

PubMed

Anzellotti, F; Franciotti, R; Bonanni, L; Tamburro, G; Perrucci, M G; Thomas, A; Pizzella, V; Romani, G L; Onofrj, M

2010-04-28

Persistent Genital Arousal Disorder (PGAD) refers to the experience of persistent sensations of genital arousal that are felt to be unprovoked, intrusive and unrelieved by one or several orgasms. It is often mistaken for hypersexuality since PGAD often results in a high frequency of sexual behaviour. At present little is known with certainty about the etiology of this condition. We described a woman with typical PGAD symptoms and orgasmic seizures that we found to be related to a specific epileptic focus. We performed a EEG/MEG and fMRI spontaneous activity study during genital arousal symptoms and after the chronic administration of 300 mg/day of topiramate. From MEG data an epileptic focus was localized in the left posterior insular gyrus (LPIG). FMRI data evidenced that sexual excitation symptoms with PGAD could be correlated with an increased functional connectivity (FC) between different brain areas: LPIG (epileptic focus), left middle frontal gyrus, left inferior and superior temporal gyrus and left inferior parietal lobe. The reduction of the FC observed after antiepileptic therapy was more marked in the left than in the right hemisphere in agreement with the lateralization identified by MEG results. Treatment completely abolished PGAD symptoms and functional hyperconnectivity. The functional hyperconnectivity found in the neuronal network including the epileptic focus could suggest a possible central mechanism for PGAD. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Alterations of apoptosis and autophagy in developing brain of rats with epilepsy: Changes in LC3, P62, Beclin-1 and Bcl-2 levels.

PubMed

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.

H.M. never again! An analysis of H.M.'s epilepsy and treatment.

PubMed

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.

Left hemisphere predominance of pilocarpine-induced rat epileptiform discharges

PubMed Central

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

Looking for complexity in quantitative semiology of frontal and temporal lobe seizures using neuroethology and graph theory.

PubMed

Bertti, Poliana; Tejada, Julian; Martins, Ana Paula Pinheiro; Dal-Cól, Maria Luiza Cleto; Terra, Vera Cristina; de Oliveira, José Antônio Cortes; Velasco, Tonicarlo Rodrigues; Sakamoto, Américo Ceiki; Garcia-Cairasco, Norberto

2014-09-01

Epileptic syndromes and seizures are the expression of complex brain systems. Because no analysis of complexity has been applied to epileptic seizure semiology, our goal was to apply neuroethology and graph analysis to the study of the complexity of behavioral manifestations of epileptic seizures in human frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). We analyzed the video recordings of 120 seizures of 18 patients with FLE and 28 seizures of 28 patients with TLE. All patients were seizure-free >1 year after surgery (Engel Class I). All patients' behavioral sequences were analyzed by means of a glossary containing all behaviors and analyzed for neuroethology (Ethomatic software). The same series were used for graph analysis (CYTOSCAPE). Behaviors, displayed as nodes, were connected by edges to other nodes according to their temporal sequence of appearance. Using neuroethology analysis, we confirmed data in the literature such as in FLE: brief/frequent seizures, complex motor behaviors, head and eye version, unilateral/bilateral tonic posturing, speech arrest, vocalization, and rapid postictal recovery and in the case of TLE: presence of epigastric aura, lateralized dystonias, impairment of consciousness/speech during ictal and postictal periods, and development of secondary generalization. Using graph analysis metrics of FLE and TLE confirmed data from flowcharts. However, because of the algorithms we used, they highlighted more powerfully the connectivity and complex associations among behaviors in a quite selective manner, depending on the origin of the seizures. The algorithms we used are commonly employed to track brain connectivity from EEG and MRI sources, which makes our study very promising for future studies of complexity in this field. Copyright © 2014 Elsevier Inc. All rights reserved.

Sporadic periventricular nodular heterotopia: Classification, phenotype and correlation with Filamin A mutations.

PubMed

Liu, Wenyu; Yan, Bo; An, Dongmei; Xiao, Jiahe; Hu, Fayun; Zhou, Dong

2017-07-01

The purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features. The study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two-sided Chi-square test and Fisher's exact t-test were used to assess associations between the distribution of PNHs and specific clinical features. Based on imaging data, patients were subdivided into three groups: (a) classical (bilateral frontal and body, n=41 patients), (b) bilateral asymmetrical or posterior (n=16) and (c) unilateral heterotopia (n=43). Most patients with classical heterotopia were females (P=0.033) and were likely to have arachnoid cysts (P=0.025) and cardiac abnormalities (P=0.041), but were mostly seizure-free. Additionally, hippocampal abnormalities (P=0.022), neurological deficits (P=0.028) and cerebellar abnormalities (P=0.005) were more common in patients with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia were prone to develop refractory epilepsy (P=0.041). FLNA mutations were identified in 8 patients. Each group's distinctive genetic mutations, epileptic discharge patterns and overall clinical outcomes confirm that the proposed classification system is reliable. These findings could not only be an indicator of a more severe morphological and clinical phenotype, but could also have clinical implications with respect to the epilepsy management and optimization of therapeutic options. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures.

PubMed

van der Kruijs, Sylvie J M; Bodde, Nynke M G; Vaessen, Maarten J; Lazeron, Richard H C; Vonck, Kristl; Boon, Paul; Hofman, Paul A M; Backes, Walter H; Aldenkamp, Albert P; Jansen, Jacobus F A

2012-03-01

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).

Myoclonic Jerks and Schizophreniform Syndrome: Case Report and Literature Review.

PubMed

Endres, Dominique; Altenmüller, Dirk-M; Feige, Bernd; Maier, Simon J; Nickel, Kathrin; Hellwig, Sabine; Rausch, Jördis; Ziegler, Christiane; Domschke, Katharina; Doerr, John P; Egger, Karl; Tebartz van Elst, Ludger

2018-01-01

Background: Schizophreniform syndromes can be divided into primary idiopathic forms as well as different secondary organic subgroups (e.g., paraepileptic, epileptic, immunological, or degenerative). Secondary epileptic explanatory approaches have often been discussed in the past, due to the high rates of electroencephalography (EEG) alterations in patients with schizophrenia. In particular, temporal lobe epilepsy is known to be associated with schizophreniform symptoms in well-described constellations. In the literature, juvenile myoclonic epilepsy has been linked to emotionally unstable personality traits, depression, anxiety, and executive dysfunction; however, the association with schizophrenia is largely unclear. Case presentation: We present the case of a 28-year-old male student suffering from mild myoclonic jerks, mainly of the upper limbs, as well as a predominant paranoid-hallucinatory syndrome with attention deficits, problems with working memory, depressive-flat mood, reduced energy, fast stimulus satiation, delusional and audible thoughts, tactile hallucinations, thought inspirations, and severe sleep disturbances. Cerebral magnetic resonance imaging and cerebrospinal fluid analyses revealed no relevant abnormalities. The routine EEG and the first EEG after sleep deprivation (under treatment with oxazepam) also returned normal findings. Video telemetry over one night, which included a partial sleep-deprivation EEG, displayed short generalized spike-wave complexes and polyspikes, associated with myoclonic jerks, after waking in the morning. Video-EEG monitoring over 5 days showed over 100 myoclonic jerks of the upper limbs, frequently with generalized spike-wave complexes with left or right accentuation. Therefore, we diagnosed juvenile myoclonic epilepsy. Discussion: This case report illustrates the importance of extended EEG diagnostics in patients with schizophreniform syndromes and myoclonic jerks. The schizophreniform symptoms in the framework of epileptiform EEG activity can be interpreted as a (para)epileptic mechanism due to local area network inhibition (LANI). Following the LANI hypothesis, paranoid hallucinatory symptoms are not due to primary excitatory activity (as myoclonic jerks are) but rather to the secondary process of hyperinhibition triggered by epileptic activity. Identifying subgroups of schizophreniform patients with comorbid epilepsy is important because of the potential benefits of optimized pharmacological treatment.

Cognitive-Behavioral Treatment of Depressed Affect among Epileptics: Preliminary Findings.

ERIC Educational Resources Information Center

Davis, Gay R.; And Others

1984-01-01

Evaluated a program where cognitive-behavioral methods were utilized in a structured learning format with clinically depressed epileptics (N=13). Results indicated that cognitive behavioral interventions result in significant decreases in depression and increases in related areas of psychosocial functioning that are maintained over time. (LLL)

Achievement and School Behavior among Children with Epilepsy.

ERIC Educational Resources Information Center

Matthews, Wendy S.; And Others

1983-01-01

Compared the school behavior of 15 epileptic children with that of diabetic and healthy children. The epileptic children were more likely to attribute the success or failure of their school performance to unknown sources of control, and to hold less positive feelings about school and their own self-worth. (Author)

Tewa Children Who Have Epilepsy: A Health Care Dilemma.

ERIC Educational Resources Information Center

DeBruyn, Lemyra M.

1990-01-01

Examines attitudes and responses toward epilepsy among families of 31 epileptic Tewa children, utilization of modern health care services, and parent reluctance to discuss traditional beliefs and healing practices. Discusses models of chronic illness behavior and the inadequacies of Indian Health Service treatment of epileptic children. Contains…

About Epilepsy.

ERIC Educational Resources Information Center

Scott, Donald

Epileptic fits, faints, and falls are described; the causes, sorts, and diagnosis of fits are detailed; and treatment that both doctor and surgeon can provide is reviewed. Further consideration is given to children with fits, the effect of fits on the mind, the care of the epileptic person, marriage and pregnancy, and the prevention of fits. Also…

Epileptic Encephalopathies and Their Relationship to Developmental Disorders: Do Spikes Cause Autism?

ERIC Educational Resources Information Center

Tharp, Barry R.

2004-01-01

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without…

Relationship between Applicant Handicap and Employment Evaluations.

ERIC Educational Resources Information Center

Farrow, Dana L.; And Others

Very little is known about discrimination against the handicapped in employment situations and the processes by which it occurs. Mature students (N=72) in personnel and behavioral science courses evaluated epileptic or non-epileptic, male or female applicants for an auto sales or receptionist position. Subjects reviewed an applicant's resume…

Vulnerability of an epileptic case to psychosis: sodium valproate with lamotrigine, forced normalization, postictal psychosis or all?

PubMed

Turan, A B; Seferoglu, M; Taskapilioglu, O; Bora, I

2012-10-01

Patients with epilepsy can be considered to be at high risk for developing psychotic disorders. Furthermore, there is association between seizure freedom or the disappearance of the interictal epileptiform events from the EEG record and the occurrence of psychotic symptoms. Also, several newer antiepileptic drugs have been reported to induce psychotic symptoms. We present a patient with epilepsy who developed psychotic symptoms under the treatment of valproic acid (VPA) and lamotrigine (LTG) combination. The mechanism underlying the association between LTG, seizure control and development of psychosis are discussed in the light of the literature.

The effect of diphenylhydantoin on metabolic and growth hormone changes during and after exercise.

PubMed Central

Chalmers, R J; Johnson, R H

1983-01-01

Metabolic and human growth hormone responses to exercise were investigated in six normal healthy subjects on two occasions with and without an oral dose of diphenylhydantoin (500 mg). Serum diphenylhydantoin concentrations were similar in all subjects and were just below the accepted therapeutic range for epileptic patients. There was no significant difference in blood lactate, pyruvate or glucose concentrations with diphenylhydantoin. Plasma free fatty acids, and blood glycerol and total ketone concentrations were greater after exercise following diphenylhydantoin. Significantly greater concentrations of human growth hormone occurred during exercise with diphenylhydantoin. Further investigation of the mechanisms by which diphenylhydantoin alters lipolysis and human growth hormone release would be of value as these metabolic and hormonal effects could influence exercise tolerance in athletics and other pursuits. PMID:6886706

Munc18-1 haploinsufficiency results in enhanced anxiety-like behavior as determined by heart rate responses in mice.

PubMed

Hager, Torben; Maroteaux, Grégoire; Pont, Paula du; Julsing, Joris; van Vliet, Rick; Stiedl, Oliver

2014-03-01

Heterozygous (HZ) missense mutations in the gene encoding syntaxin binding protein 1 (Stxbp1 or Munc18-1), a presynaptic protein essential for neurotransmitter release, causes early infantile epileptic encephalopathy, abnormal brain structure and mental retardation in humans. Here we investigated whether the mouse model mimics symptoms of the human phenotype. The effects of the deletion of munc18-1 were studied in HZ and wild-type (WT) mice based on heart rate (HR) and its variability (HRV) as independent measures to expand previous behavioral results of enhanced anxiety and impaired emotional learning suggesting mild cognitive impairments. HR responses were assessed during novelty exposure, during the expression and extinction of conditioned tone-dependent fear and during the diurnal phase. Novelty exposure yielded no differences in activity patterns between the two genotypes, while maximum HR differed significantly (WT: 770 bpm; HZ: 790 bpm). Retention tests after both auditory delay and trace fear conditioning showed a delayed extinction of the conditioned HR response in HZ mice compared to WT mice. Since the HR versus HRV correlation and HR dynamics assessed by nonlinear methods revealed similar function in HZ and WT mice, the higher HR responses of munc18-1 HZ mice to different emotional challenges cannot be attributed to differences in autonomic nervous system function. Thus, in contrast to the adverse consequences of deletion of a single allele of munc18-1 in humans, C57BL/6J mice show enhanced anxiety responses based on HR adjustments that extend previous results on the behavioral level without support of cognitive impairment, epileptic seizures and autonomic dysregulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Determining the degree of synchronism for intermittent phase synchronization in human electroencephalography data

NASA Astrophysics Data System (ADS)

Koloskova, A. D.; Moskalenko, O. I.

2017-05-01

The phenomenon of intermittent phase synchronization during development of epileptic activity in human beings has been discovered based on EEG data. The presence of synchronous behavior phases has been detected both during spike-wave discharges and in the regions of background activity of the brain. The degree of synchronism in the intermittent phase-synchronization regime in both cases has been determined, and it has been established that spike-wave discharges are characterized by a higher degree of synchronism than exists in the regions of background activity of the brain. To determine the degree of synchronism, a modified method of evaluating zero conditional Lyapunov exponents from time series is proposed.

Infantile masturbation and paroxysmal disorders.

PubMed

Omran, Mohammadreza Salehi; Ghofrani, Mohammad; Juibary, Ali Ghabeli

2008-02-01

A recurrent paroxysmal presentation in children leads to different diagnoses and among them are neurologic and cardiac etiologies. Infantile masturbation is not a well known entity and cannot be differentiated easily from other disorders. Aim of this study is to elucidate and differentiate this condition from epileptic seizures. We report 3 cases of 10 to 30 mth old girls of infantile masturbation that their symptoms initiated at 2, 3 and 8 mth of age. These present with contraction and extension of lower extremities, scissoring of legs, perspiration, changing face color. In 2 cases body rocking and legs rubbing initiated then there after. Masturbation is one of the paroxysmal non-epileptic conditions of early infancy and is in differential diagnosis of epileptic seizures.

Crowdsourcing reproducible seizure forecasting in human and canine epilepsy

PubMed Central

Wagenaar, Joost; Abbot, Drew; Adkins, Phillip; Bosshard, Simone C.; Chen, Min; Tieng, Quang M.; He, Jialune; Muñoz-Almaraz, F. J.; Botella-Rocamora, Paloma; Pardo, Juan; Zamora-Martinez, Francisco; Hills, Michael; Wu, Wei; Korshunova, Iryna; Cukierski, Will; Vite, Charles; Patterson, Edward E.; Litt, Brian; Worrell, Gregory A.

2016-01-01

See Mormann and Andrzejak (doi:10.1093/brain/aww091) for a scientific commentary on this article.   Accurate forecasting of epileptic seizures has the potential to transform clinical epilepsy care. However, progress toward reliable seizure forecasting has been hampered by lack of open access to long duration recordings with an adequate number of seizures for investigators to rigorously compare algorithms and results. A seizure forecasting competition was conducted on kaggle.com using open access chronic ambulatory intracranial electroencephalography from five canines with naturally occurring epilepsy and two humans undergoing prolonged wide bandwidth intracranial electroencephalographic monitoring. Data were provided to participants as 10-min interictal and preictal clips, with approximately half of the 60 GB data bundle labelled (interictal/preictal) for algorithm training and half unlabelled for evaluation. The contestants developed custom algorithms and uploaded their classifications (interictal/preictal) for the unknown testing data, and a randomly selected 40% of data segments were scored and results broadcasted on a public leader board. The contest ran from August to November 2014, and 654 participants submitted 17 856 classifications of the unlabelled test data. The top performing entry scored 0.84 area under the classification curve. Following the contest, additional held-out unlabelled data clips were provided to the top 10 participants and they submitted classifications for the new unseen data. The resulting area under the classification curves were well above chance forecasting, but did show a mean 6.54 ± 2.45% (min, max: 0.30, 20.2) decline in performance. The kaggle.com model using open access data and algorithms generated reproducible research that advanced seizure forecasting. The overall performance from multiple contestants on unseen data was better than a random predictor, and demonstrates the feasibility of seizure forecasting in canine and human epilepsy. PMID:27034258

Epileptic Hypergraphia: The Impact of Prolific Writing on Language Creativity

ERIC Educational Resources Information Center

Ammari, Elham H.

2012-01-01

Catalyzed academic concerns have been shown so far to tackle the issue of temporal lobe epileptic hypergraphia and the extent of its creativity. Temporal lobe epilepsy hence, (TLE) as a neurological brain disorder, has captured the attention of concerned scholars ever since. A constellation of TLE and its cohorts have baffled scientists,…

False Negatives, Canter's Background Interference Procedure, the Trail Making Test, and Epileptics.

ERIC Educational Resources Information Center

McKinzey, Ronald K.; And Others

1985-01-01

Results of correlation studies of 141 adult epileptics' scores on the Background Interference Procedure (BIP) indicated that the BIP often does not agree with abnormal neurological diagnoses but often does agree with psychiatric diagnoses of Organic Brain Syndrome (OBS). Suggests that future BIP validity studies include a behavioral measure of OBS…

Unusual association of SCN2A epileptic encephalopathy with severe cortical dysplasia detected by prenatal MRI.

PubMed

Bernardo, Silvia; Marchionni, Enrica; Prudente, Sabrina; De Liso, Paola; Spalice, Alberto; Giancotti, Antonella; Manganaro, Lucia; Pizzuti, Antonio

2017-05-01

We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the α II -subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Detection of Epileptic Seizure Event and Onset Using EEG

PubMed Central

Ahammad, Nabeel; Fathima, Thasneem; Joseph, Paul

2014-01-01

This study proposes a method of automatic detection of epileptic seizure event and onset using wavelet based features and certain statistical features without wavelet decomposition. Normal and epileptic EEG signals were classified using linear classifier. For seizure event detection, Bonn University EEG database has been used. Three types of EEG signals (EEG signal recorded from healthy volunteer with eye open, epilepsy patients in the epileptogenic zone during a seizure-free interval, and epilepsy patients during epileptic seizures) were classified. Important features such as energy, entropy, standard deviation, maximum, minimum, and mean at different subbands were computed and classification was done using linear classifier. The performance of classifier was determined in terms of specificity, sensitivity, and accuracy. The overall accuracy was 84.2%. In the case of seizure onset detection, the database used is CHB-MIT scalp EEG database. Along with wavelet based features, interquartile range (IQR) and mean absolute deviation (MAD) without wavelet decomposition were extracted. Latency was used to study the performance of seizure onset detection. Classifier gave a sensitivity of 98.5% with an average latency of 1.76 seconds. PMID:24616892

Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use

PubMed Central

Levin, Harvey S.; Chiang, Sharon

2015-01-01

Abstract Neuroimaging studies of functional connectivity using graph theory have furthered our understanding of the network structure in temporal lobe epilepsy (TLE). Brain network effects of anti-epileptic drugs could influence such studies, but have not been systematically studied. Resting-state functional MRI was analyzed in 25 patients with TLE using graph theory analysis. Patients were divided into two groups based on anti-epileptic medication use: those taking carbamazepine/oxcarbazepine (CBZ/OXC) (n=9) and those not taking CBZ/OXC (n=16) as a part of their medication regimen. The following graph topology metrics were analyzed: global efficiency, betweenness centrality (BC), clustering coefficient, and small-world index. Multiple linear regression was used to examine the association of CBZ/OXC with graph topology. The two groups did not differ from each other based on epilepsy characteristics. Use of CBZ/OXC was associated with a lower BC. Longer epilepsy duration was also associated with a lower BC. These findings can inform graph theory-based studies in patients with TLE. The changes observed are discussed in relation to the anti-epileptic mechanism of action and adverse effects of CBZ/OXC. PMID:25492633

Psychogenic Non-epileptic Seizures: An Updated Primer.

PubMed

Baslet, Gaston; Seshadri, Ashok; Bermeo-Ovalle, Adriana; Willment, Kim; Myers, Lorna

2016-01-01

Psychogenic non-epileptic seizures are the most common paroxysmal event misdiagnosed as epilepsy. They significantly affect quality of life, functional status, and use of medical resources. The goal of this review is to provide guidance to psychiatrists and other mental health professionals in the understanding and practical management of this condition. An abundance of new reports on the pathogenesis and effective treatments have become available over the last decade, yet specific barriers impede the fluid transition to treatment and remain an important challenge in the management of patients with psychogenic non-epileptic seizures. In the context of these difficulties, we initially present background information on psychogenic non-epileptic seizures covering their historic context, epidemiology, etiologic factors (including psychiatric, neuromedical, and neuropsychological factors), and current neurobiological models. Updated evidence-based treatments are discussed along with data on long-term outcomes. We also provide practical tools to help clinicians navigate differential diagnoses, establish their interdisciplinary roles, communicate the diagnosis, deliver treatment, and sort out commonly encountered challenges in the management of this condition. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

The Inhibitory Effects of Npas4 on Seizures in Pilocarpine-Induced Epileptic Rats

PubMed Central

Guo, Jiamei; Yang, Guang; Long, Xianghua; Hu, Rong; Shen, Wenjing; Wang, Xuefeng; Zeng, Kebin

2014-01-01

To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats. PMID:25536221

The inhibitory effects of Npas4 on seizures in pilocarpine-induced epileptic rats.

PubMed

Wang, Dan; Ren, Min; Guo, Jiamei; Yang, Guang; Long, Xianghua; Hu, Rong; Shen, Wenjing; Wang, Xuefeng; Zeng, Kebin

2014-01-01

To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats.

The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

PubMed

Eldin, Essam Eldin Mohamed Nour; Elshebiny, Hosam Abdel-Fattah; Mohamed, Tarek Mostafa; Abdel-Aziz, Mohamed Abdel-Azim; El-Readi, Mahmoud Zaki

2016-01-01

Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression

PubMed Central

Kim, Hyun-Ji; Jeong, Myong-Ho; Kim, Kyung-Ran; Jung, Chang-Yun; Lee, Seul-Yi; Kim, Hanna; Koh, Jewoo; Vuong, Tuan Anh; Jung, Seungmoon; Yang, Hyunwoo; Park, Su-Kyung; Choi, Dahee; Kim, Sung Hun; Kang, KyeongJin; Sohn, Jong-Woo; Park, Joo Min; Jeon, Daejong; Koo, Seung-Hoi; Ho, Won-Kyung; Kang, Jong-Sun; Kim, Seong-Tae; Cho, Hana

2016-01-01

KCNQ channels are critical determinants of neuronal excitability, thus emerging as a novel target of anti-epileptic drugs. To date, the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors, Ca2+/CaM, and protein kinase C. Here we demonstrate that methylation of KCNQ by protein arginine methyltransferase 1 (Prmt1) positively regulates KCNQ channel activity, thereby preventing neuronal hyperexcitability. Prmt1+/- mice exhibit epileptic seizures. Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP2 binding, and Prmt1 depletion lowers PIP2 affinity of KCNQ2 channels and thereby the channel activities. Consistently, exogenous PIP2 addition to Prmt1+/- neurons restores KCNQ currents and neuronal excitability to the WT level. Collectively, we propose that Prmt1-dependent facilitation of KCNQ-PIP2 interaction underlies the positive regulation of KCNQ activity by arginine methylation, which may serve as a key target for prevention of neuronal hyperexcitability and seizures. DOI: http://dx.doi.org/10.7554/eLife.17159.001 PMID:27466704

Intrathecal immunoglobulin synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic').

PubMed

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.

Differential epileptogenic potentials of selective mu and delta opiate receptor agonists.

PubMed

Haffmans, J; Dzoljic, M R

1983-01-01

By using electroencephalographic (EEG) and electromyographic recordings in anaesthetized and free-moving rats, two opioid peptides, known as selective agonists for mu and delta opiate receptors, respectively, were examined for their epileptogenic properties. The delta receptor peptide (DSTLE, 4.6-18.6 nmol, intraventricularly, ivt), a putative delta opiate agonist, produced a dose-related increase of myoclonic contractions (MC) with epileptic discharges in anaesthetized rats and severe wet dog shakes, with occasionally falling down, in free-moving animals. Morphiceptin, a specific mu opiate agonist, used in equimolar doses and under the same experimental conditions, had a significantly less pronounced effect on the number of MC and epileptiform EEG phenomena. Similarly, DSTLE (18.6 nmol) injected in the CA2 area of the hippocampus, a region with a nearly equal distribution of mu and delta opiate receptors, induced epileptic discharges in anaesthetized and free-moving rats, while an equimolar dose of morphiceptin had no significant effect. It is suggested that the epileptiform activity of opioid peptides is mainly due to an activation of delta opiate receptors in the central nervous system.

The effects of lossy compression on diagnostically relevant seizure information in EEG signals.

PubMed

Higgins, G; McGinley, B; Faul, S; McEvoy, R P; Glavin, M; Marnane, W P; Jones, E

2013-01-01

This paper examines the effects of compression on EEG signals, in the context of automated detection of epileptic seizures. Specifically, it examines the use of lossy compression on EEG signals in order to reduce the amount of data which has to be transmitted or stored, while having as little impact as possible on the information in the signal relevant to diagnosing epileptic seizures. Two popular compression methods, JPEG2000 and SPIHT, were used. A range of compression levels was selected for both algorithms in order to compress the signals with varying degrees of loss. This compression was applied to the database of epileptiform data provided by the University of Freiburg, Germany. The real-time EEG analysis for event detection automated seizure detection system was used in place of a trained clinician for scoring the reconstructed data. Results demonstrate that compression by a factor of up to 120:1 can be achieved, with minimal loss in seizure detection performance as measured by the area under the receiver operating characteristic curve of the seizure detection system.

Effect of infrared laser irradiation on amino acid neurotransmitters in an epileptic animal model induced by pilocarpine.

PubMed

Radwan, Nasr Mahmoud; El Hay Ahmed, Nawal Abd; Ibrahim, Khayria Mansour; Khedr, Mona Emam; Aziz, Mona A; Khadrawy, Yasser Ashry

2009-06-01

The aim of the present study was to investigate the effect of daily laser irradiation on the levels of amino acid neurotransmitters in the cortex and hippocampus in an epileptic animal model induced by pilocarpine. It has been claimed that at specific wavelengths and energy densities, laser irradiation is a novel and useful tool for the treatment of peripheral and central nervous system injuries and disorders. Adult male albino rats were divided into three groups: control rats, pilocarpinized rats (epileptic animal model), and pilocarpinized rats treated daily with laser irradiation (90 mW at 830 nm) for 7 d. The following parameters were assayed in cortex and hippocampus: amino acid neurotransmitters (excitatory: glutamic acid and aspartate; and inhibitory: gamma-aminobutyric acid [GABA], glycine, and taurine) by high-performance liquid chromatography (HPLC), glucose content, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), using a spectrophotometer. Significant increases in the concentrations of glutamic acid, glutamine, glycine, and taurine were recorded in the cortices of pilocarpinized rats, and they returned to initial levels after laser treatment. In the hippocampus, a moderate increase in aspartate accompanied by a significant increase in glycine were observed in the epileptic animal model, and these dropped to near-control values after laser treatment. In addition, a significant increase in cortical AST activity and a significant decrease in ALT activity and glucose content were obtained in the pilocarpinized animals and pilocarpinized rats treated with laser irradiation. In the hippocampus, significant decreases in the activity of AST and ALT and glucose content were recorded in the epileptic animals and in the epileptic animals treated with laser irradiation. Based on the results obtained in this study, it may be suggested that nearinfrared laser irradiation may reverse the neurochemical changes in amino acid neurotransmitters induced by pilocarpine.

First Analysis of the Association Between CYP3A4/5, ABCB1 Genetic Polymorphisms and Oxcarbazepine Metabolism and Transport in Chinese Epileptic Patients with Oxcarbazepine Monotherapy and Bitherapy.

PubMed

Wang, Ping; Yin, Tao; Ma, Hong-ying; Liu, Dan-Qi; Sheng, Yangh-ao; Zhou, Bo-Ting

2015-01-01

Oxcarbazepine (OXC) is widely used in anti-epileptic treatment. Cytochrome P450 3A4 (CYP3A4), cytochrome P450 3A5(CYP3A5), and ATP-binding cassette sub-family B member 1 (ABCB1) are potential genes involved in OXC metabolisms and transport in vivo. This study aims to examine the genetic effects of CYP3A4, CYP3A5, and ABCB1 on OXC metabolism and transport in Chinese epileptic patients using OXC as monotherapy and bitherapy with lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). Sixty-six Chinese epileptic patients were recruited from Xiangya Hospital Central South University, of whom 40 patients were receiving OXC monotherapy, 11 patients were placed in the OXC bitherapy group combined with one enzyme-inducing anti-epileptic drugs (LTG or LEV), and 15 patients were placed in the OXC bitherapy group combined with VPA. Oxcarbazepine and its main metabolite 10-hydrocarbazepine (MHD) plasma concentrations were measured using high performance liquid chromatography (HPLC)-UV method. In addition, eight single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, ABCB1 gene were genotyped by polymerase chain reaction-improved multiple ligase detection reaction (PCR-iMLDR). In the OXC+VPA group, ABCB1 rs2032582 and rs2032582-rs10234411-rs1045642 TAG haplotype were associated with MHD and MHD+OXC plasma concentration before permutation test. In OXC monotherapy and OXC+ LTG/LEV groups, no significant association between genetic polymorphisms in CYP3A4/5, ABCB1 gene and OXC plasma concentration parameters were observed. CYP3A4/5 and ABCB1 genetic variants might not take part in the metabolism and transport of MHD and OXC among epileptic patients using OXC monotherapy and bitherapy in combination with LEV, LTG or VPA.

Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

PubMed

Simoens, Steven

2011-01-01

This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

Study on the Relationships between Intrinsic Functional Connectivity of the Default Mode Network and Transient Epileptic Activity

PubMed Central

Lopes, Renaud; Moeller, Friederike; Besson, Pierre; Ogez, François; Szurhaj, William; Leclerc, Xavier; Siniatchkin, Michael; Chipaux, Mathilde; Derambure, Philippe; Tyvaert, Louise

2014-01-01

Rationale: Simultaneous recording of electroencephalogram and functional MRI (EEG–fMRI) is a powerful tool for localizing epileptic networks via the detection of hemodynamic changes correlated with interictal epileptic discharges (IEDs). fMRI can be used to study the long-lasting effect of epileptic activity by assessing stationary functional connectivity during the resting-state period [especially, the connectivity of the default mode network (DMN)]. Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) are associated with low responsiveness and disruption of DMN activity. A dynamic functional connectivity approach might enable us to determine the effect of IEDs on DMN connectivity and to better understand the correlation between DMN connectivity changes and altered consciousness. Method: We studied dynamic changes in DMN intrinsic connectivity and their relation to IEDs. Six IGE patients (with generalized spike and slow-waves) and 6 TLE patients (with unilateral left temporal spikes) were included. Functional connectivity before, during, and after IEDs was estimated using a sliding window approach and compared with the baseline period. Results: No dependence on window size was observed. The baseline DMN connectivity was decreased in the left hemisphere (ipsilateral to the epileptic focus) in TLEs and was less strong but remained bilateral in IGEs. We observed an overall increase in DMN intrinsic connectivity prior to the onset of IEDs in both IGEs and TLEs. After IEDs in TLEs, we found that DMN connectivity increased before it returned to baseline values. Most of the DMN regions with increased connectivity before and after IEDs were lateralized to the left hemisphere in TLE (i.e., ipsilateral to the epileptic focus). Conclusion: Results suggest that DMN connectivity may facilitate IED generation and may be affected at the time of the IED. However, these results need to be confirmed in a larger independent cohort. PMID:25346721

Cross-sectional study of the hospital management of adult patients with a suspected seizure (EPIC2).

PubMed

Dickson, Jon Mark; Dudhill, Hannah; Shewan, Jane; Mason, Sue; Grünewald, Richard A; Reuber, Markus

2017-07-13

To determine the clinical characteristics, management and outcomes of patients taken to hospital by emergency ambulance after a suspected seizure. Quantitative cross-sectional retrospective study of a consecutive series of patients. An acute hospital trust in a large city in England. In 2012-2013, the regions' ambulance service managed 605 481 emergency incidents, 74 141/605 481 originated from Sheffield (a large city in the region), 2121/74 141 (2.9%) were suspected seizures and 178/2121 occurred in May 2012. We undertook detailed analysis of the medical records of the 91/178 patients who were transported to the city's acute hospital. After undertaking a retrospective review of the medical records, the best available aetiological explanation for the seizures was determined. The best available aetiological explanation for 74.7% (68/91) of the incidents was an epileptic seizure, 11.0% (10/91) were psychogenic non-epileptic seizures and 9.9% (9/91) were cardiogenic events. The epileptic seizures fall into the following four categories: first epileptic seizure (13.2%, 12/91), epileptic seizure with a historical diagnosis of epilepsy (30.8%, 28/91), recurrent epileptic seizures without a historical diagnosis of epilepsy (20.9%, 19/91) and acute symptomatic seizures (9.9%, 9/91). Of those with seizures (excluding cardiogenic events), 2.4% (2/82) of patients were seizing on arrival in the Emergency Department (ED), 19.5% (16/82) were postictal and 69.5% (57/82) were alert. 63.4% (52/82) were discharged at the end of their ED attendance and 36.5% (19/52) of these had no referral or follow-up. Most suspected seizures are epileptic seizures but this is a diagnostically heterogeneous group. Only a small minority of patients require emergency medical care but most are transported to hospital. Few patients receive expert review and many are discharged home without referral to a specialist leaving them at risk of further seizures and the associated morbidity, mortality and health services costs of poorly controlled epilepsy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics

NASA Astrophysics Data System (ADS)

Serletis, Demitre; Bardakjian, Berj L.; Valiante, Taufik A.; Carlen, Peter L.

2012-10-01

Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/fγ noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders. This paper is based on chapter 5 of Serletis (2010 PhD Dissertation Department of Physiology, Institute of Biomaterials and Biomedical Engineering, University of Toronto).

Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy

PubMed Central

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

Metabolic networks in epilepsy by MR spectroscopic imaging.

PubMed

Pan, J W; Spencer, D D; Kuzniecky, R; Duckrow, R B; Hetherington, H; Spencer, S S

2012-12-01

The concept of an epileptic network has long been suggested from both animal and human studies of epilepsy. Based on the common observation that the MR spectroscopic imaging measure of NAA/Cr is sensitive to neuronal function and injury, we use this parameter to assess for the presence of a metabolic network in mesial temporal lobe epilepsy (MTLE) patients. A multivariate factor analysis is performed with controls and MTLE patients, using NAA/Cr measures from 12 loci: the bilateral hippocampi, thalami, basal ganglia, and insula. The factor analysis determines which and to what extent these loci are metabolically covarying. We extract two independent factors that explain the data's variability in control and MTLE patients. In controls, these factors characterize a 'thalamic' and 'dominant subcortical' function. The MTLE patients also exhibit a 'thalamic' factor, in addition to a second factor involving the ipsilateral insula and bilateral basal ganglia. These data suggest that MTLE patients demonstrate a metabolic network that involves the thalami, also seen in controls. The MTLE patients also display a second set of metabolically covarying regions that may be a manifestation of the epileptic network that characterizes limbic seizure propagation. © 2012 John Wiley & Sons A/S.

Magnetic resonance volumetry of the hippocampus in familial spontaneous epileptic cats.

PubMed

Mizoguchi, Shunta; Hasegawa, Daisuke; Kuwabara, Takayuki; Hamamoto, Yuji; Ogawa, Fukie; Fujiwara, Aki; Matsuki, Naoaki; Fujita, Michio

2014-12-01

A strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010. The electroencephalographic features suggested that an epileptogenic zone is present in the mesial temporal structures (i.e., amygdala and/or hippocampus). In this study, visual evaluations and quantitative analyses were performed by using 3D MR hippocampal volumetry in comparing FSECs with age-matched controls. Visual hippocampal asymmetries were seen in 8 of 14 (57.1%) FSECs. The FSEC group showed a significantly higher asymmetric ratio (4.15%) than the control group (0.99%). The smaller side of hippocampal volume (HV) (0.206 cm(3)) in FSECs was significantly smaller than the mean HV in controls (0.227 cm(3)). However, the means of left and right HVs and total HVs in FSECs showed no differences because the laterality of hippocampal atrophy was different in each individual. Therefore, since FSECs represent a true model of spontaneous epilepsy, hippocampal volumetry should be evaluated in each individual as well as in human patients. The significant asymmetry of HV suggests the potential for hippocampal atrophy in FSECs. Copyright © 2014 Elsevier B.V. All rights reserved.

Verbal Memory Compensation: Application to Left and Right Temporal Lobe Epileptic Patients

ERIC Educational Resources Information Center

Bresson, Christel; Lespinet-Najib, Veronique; Rougier, Alain; Claverie, Bernard; N'Kaoua, Bernard

2007-01-01

This study investigates the compensatory impact of cognitive aids on left and right temporal lobe epileptic patients suffering from verbal memory disorders, who were candidates for surgery. Cognitive aids are defined in the levels-of-processing framework and deal with the depth of encoding, the elaboration of information, and the use of retrieval…

Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

ERIC Educational Resources Information Center

Tan, Siang-Yang

1986-01-01

Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

Seizure, Fit or Attack? The Use of Diagnostic Labels by Patients with Epileptic or Non-Epileptic Seizures

ERIC Educational Resources Information Center

Plug, Leendert; Sharrack, Basil; Reuber, Markus

2010-01-01

We present an analysis of the use of diagnostic labels such as "seizure", "attack", "fit", and "blackout" by patients who experience seizures. While previous research on patients' preferences for diagnostic terminology has relied on questionnaires, we assess patients' own preferences and their responses to a doctor's use of different labels…

Surgical Treatment of Pediatric Epileptic Encephalopathies

PubMed Central

Fridley, J.; Reddy, G.; Curry, D.; Agadi, S.

2013-01-01

Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed. PMID:24288601

Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain.

PubMed

Bonansco, Christian; Fuenzalida, Marco

2016-01-01

Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

PubMed Central

Bonansco, Christian; Fuenzalida, Marco

2016-01-01

Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID:27006834

The influence of hubs in the structure of a neuronal network during an epileptic seizure

NASA Astrophysics Data System (ADS)

Rodrigues, Abner Cardoso; Cerdeira, Hilda A.; Machado, Birajara Soares

2016-02-01

In this work, we propose changes in the structure of a neuronal network with the intention to provoke strong synchronization to simulate episodes of epileptic seizure. Starting with a network of Izhikevich neurons we slowly increase the number of connections in selected nodes in a controlled way, to produce (or not) hubs. We study how these structures alter the synchronization on the spike firings interval, on individual neurons as well as on mean values, as a function of the concentration of connections for random and non-random (hubs) distribution. We also analyze how the post-ictal signal varies for the different distributions. We conclude that a network with hubs is more appropriate to represent an epileptic state.

Amygdala Volumetry in Patients with Temporal Lobe Epilepsy and Normal Magnetic Resonance Imaging

PubMed Central

Singh, Paramdeep; Kaur, Rupinderjeet; Saggar, Kavita; Singh, Gagandeep; Aggarwal, Simmi

2016-01-01

Summary Background It has been suggested that the pathophysiology of temporal lobe epilepsy may relate to abnormalities in various brain structures, including the amygdala. Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NMRI) represent a challenge for diagnosis of the underlying abnormality and for presurgical evaluation. To date, however, only few studies have used quantitative structural Magnetic Resonance Imaging-based techniques to examine amygdalar pathology in these patients. Material/Methods Based on clinical examination, 24-hour video EEG recordings and MRI findings, 50 patients with EEG lateralized TLE and normal structural Magnetic Resonance Imaging results were included in this study. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas and hippocampi were conducted in 50 non-epileptic controls (age 7–79 years) and 50 patients with MTLE with normal MRI on a 1.5-Tesla scanner. Visual assessment and amygdalar volumetry were performed on oblique coronal T2W and T1W MP-RAGE images respectively. The T2 relaxation times were measured using the 16-echo Carr-Purcell-Meiboom-Gill sequence (TE, 22–352). Volumetric data were normalized for variation in head size between individuals. Results were assessed by SSPS statistic program. Results Individual manual volumetric analysis confirmed statistically significant amygdala enlargement (AE) in eight (16%) patients. Overall, among all patients with AE and a defined epileptic focus, 7 had predominant increased volume ipsilateral to the epileptic focus. The T2 relaxometry demonstrated no hyperintense signal of the amygdala in any patient with significant AE. Conclusions This paper presented AE in a few patients with TLE and normal MRI. These findings support the hypothesis that there might be a subgroup of patients with MTLE-NMRI in which the enlarged amygdala could be related to the epileptogenic process. PMID:27231493

CHD2 variants are a risk factor for photosensitivity in epilepsy

PubMed Central

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 into human cortical excitability. PMID:25783594

Patient-Specific Detection of Cerebral Blood Flow Alterations as Assessed by Arterial Spin Labeling in Drug-Resistant Epileptic Patients

PubMed Central

Boscolo Galazzo, Ilaria; Storti, Silvia Francesca; Del Felice, Alessandra; Pizzini, Francesca Benedetta; Arcaro, Chiara; Formaggio, Emanuela; Mai, Roberto; Chappell, Michael; Beltramello, Alberto; Manganotti, Paolo

2015-01-01

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients. PMID:25946055

Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES).

PubMed

Pardo, Carlos A; Nabbout, Rima; Galanopoulou, Aristea S

2014-04-01

The mechanisms of epileptogenesis in pediatric epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific epileptic syndromes, such as infantile spasms and West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as infections or fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric epileptic syndromes in which acute and rapidly progressive encephalopathies preceded by fever and/or infections, such as febrile infection-related epilepsy syndrome, or in chronic progressive encephalopathies, such as Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8(+) T lymphocytes and neuroglial responses has been demonstrated in Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to steroids and adrenocorticotropic hormone of infantile spasms, or preceding fever or infection in FIRES, may support a potential role of neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric epileptic syndromes.

Chronic deficit in the expression of voltage-gated potassium channel Kv3.4 subunit in the hippocampus of pilocarpine-treated epileptic rats

PubMed Central

Pacheco Otalora, Luis F.; Skinner, Frank; Oliveira, Mauro S.; Dotson, Bianca Farrel; Arshadmansab, Massoud F.; Pandari, Tarun; Garcia, Ileana; Robles, Leslie; Rosas, Gerardo; Mello, Carlos F.; Ermolinsky, Boris S.; Garrido-Sanabria, Emilio R.

2010-01-01

Voltage gated K+ channels (Kv) are a highly diverse group of channels critical in determining neuronal excitability. Deficits of Kv channel subunit expression and function have been implicated in the pathogenesis of epilepsy. In this study, we investigate whether the expression of the specific subunit Kv3.4 is affected during epileptogenesis following pilocarpine-induced status epilepticus. For this purpose, we used immunohistochemistry, Western blotting assays and comparative analysis of gene expression using TaqMan-based probes and delta-delta cycle threshold (Δ ΔCT) method of quantitative real-time polymerase chain reaction (qPCR) technique in samples obtained from age-matched control and epileptic rats. A marked down-regulation of Kv3.4 immunoreactivity was detected in the stratum lucidum and hilus of dentate gyrus in areas corresponding to the mossy fiber system of chronically epileptic rats. Correspondingly, a 20% reduction of Kv3.4 protein levels was detected in the hippocampus of chronic epileptic rats. Real-time quantitative PCR analysis of gene expression revealed that a significant 33% reduction of transcripts for Kv3.4 (gene Kcnc4) occurred after 1 month of pilocarpine-induced status epilepticus and persisted during the chronic phase of the model. These data indicate a reduced expression of Kv3.4 channels at protein and transcript levels in the epileptic hippocampus. Down-regulation of Kv3.4 in mossy fibers may contribute to enhanced presynaptic excitability leading to recurrent seizures in the pilocarpine model of temporal lobe epilepsy. PMID:20971086

Seizures and epilepsy in elderly patients of an urban area of Iran: clinical manifestation, differential diagnosis, etiology, and epilepsy subtypes.

PubMed

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.

Epileptic seizures in Neuro-Behcet disease: why some patients develop seizure and others not?

PubMed

Kutlu, Gulnihal; Semercioglu, Sencer; Ucler, Serap; Erdal, Abidin; Inan, Levent E

2015-03-01

Behcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. All files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. The mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. CVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Ictal speech and language dysfunction in adult epilepsy: Clinical study of 95 seizures.

PubMed

Dussaule, C; Cauquil, C; Flamand-Roze, C; Gagnepain, J-P; Bouilleret, V; Denier, C; Masnou, P

2017-04-01

To analyze the semiological characteristics of the language and speech disorders arising during epileptic seizures, and to describe the patterns of language and speech disorders that can predict laterality of the epileptic focus. This study retrospectively analyzed 95 consecutive videos of seizures with language and/or speech disorders in 44 patients admitted for diagnostic video-EEG monitoring. Laterality of the epileptic focus was defined according to electro-clinical correlation studies and structural and functional neuroimaging findings. Language and speech disorders were analyzed by a neurologist and a speech therapist blinded to these data. Language and/or speech disorders were subdivided into eight dynamic patterns: pure anterior aphasia; anterior aphasia and vocal; anterior aphasia and "arthria"; pure posterior aphasia; posterior aphasia and vocal; pure vocal; vocal and arthria; and pure arthria. The epileptic focus was in the left hemisphere in more than 4/5 of seizures presenting with pure anterior aphasia or pure posterior aphasia patterns, while discharges originated in the right hemisphere in almost 2/3 of seizures presenting with a pure vocal pattern. No laterality value was found for the other patterns. Classification of the language and speech disorders arising during epileptic seizures into dynamic patterns may be useful for the optimal analysis of anatomo-electro-clinical correlations. In addition, our research has led to the development of standardized tests for analyses of language and speech disorders arising during seizures that can be conducted during video-EEG sessions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Use of anti-epileptic drugs in a tertiary care hospital of Eastern India with emphasis on epilepsy due to neurocysticercosis.

PubMed

Sil, Amrita; Das, Kamalesh; Das, Nilay K; Chakraborty, Dibyendu; Mazumdar, Goutameswar; Tripathi, Santanu K

2012-01-01

Epilepsy is a chronic disease and neurocysticercosis is an important cause of secondary seizures. Its therapy is modified by a number of parameters and thus the pattern of anti-epileptic drugs used varies in different clinical settings. It was our objective to evaluate clinico-demographic and treatment profile of epilepsy patients attending neurology outpatient department, efficacy and side-effect profile of anti-epileptic drugs with special emphasis on epilepsy resulting from neurocysticercosis. This was a cross-sectional descriptive study of epilepsy patients over four months in neurology outpatient department. Clinico-biological data were obtained by interrogating patients and from recorded data using standard case-report form. 79 patients were studied with 54.43% having primary etiology, 40.51% having seizures secondary to neurocysticercosis. 81% had generalized tonic-clonic seizure, 17.7% partial and 1.3% myoclonic seizures. Phenytoin (86.08%), valproate (30.38%), clobazam (26.58%) and carbamazepine (10.13%) were used either alone or in combination, with no use of anthelmintics even in cases of neurocysticercosis. Control of seizure was obtained in 79.7% with significant decrease in seizure frequency from 2.92 to 0.51 (P < 0.0001). Weight loss, nausea, decreased appetite, increased sleep, drowsiness, tremors were found to be significantly associated (P < 0.05) with phenytoin use. Phenytoin is the primary antiepileptic in spite of its side effects; though addition of other anti-epileptic drugs (valproate, clobazam) was required for better seizure control. Cases of neurocysticercosis respond to anti-epileptic drugs without addition of anthelmintics. Side effects observed were mostly neurological in nature.

[Epileptic insults, cerebral infarction and rhabdomyolysis as complications of amphetamine use].

PubMed

Roebroek, R M; Korten, J J

1996-01-27

In a 16-year-old boy with acute generalised epileptic convulsions, cerebral infarction and rhabdomyolysis were diagnosed. The urine was positive for amphetamine. Until that moment the patient had denied using drugs. He recovered and was discharged after nine days. Recreational use of ecstasy (methylenedioxymethamphetamine) and other amphetamine derivatives is gaining popularity worldwide. This drug abuse is rarely reported spontaneously.

Consciousness in Non-Epileptic Attack Disorder

PubMed Central

Reuber, M.; Kurthen, M.

2011-01-01

Non-epileptic attack disorder (NEAD) is one of the most important differential diagnoses of epilepsy. Impairment of consciousness is the key feature of non-epileptic attacks (NEAs). The first half of this review summarises the clinical research literature featuring observations relating to consciousness in NEAD. The second half places this evidence in the wider context of the recent discourse on consciousness in neuroscience and the philosophy of mind. We argue that studies of consciousness should not only distinguish between the ‘level’ and ‘content’ of consciousness but also between ‘phenomenal consciousness’ (consciousness of states it somehow “feels to be like”) and ‘access consciousness’ (having certain ‘higher’ cognitive processes at one’s disposal). The existing evidence shows that there is a great intra- and interindividual variability of NEA experience. However, in most NEAs phenomenal experience – and, as a precondition for that experience, vigilance or wakefulness – is reduced to a lesser degree than in those epileptic seizures involving impairment of consciousness. In fact, complete loss of “consciousness” is the exception rather than the rule in NEAs. Patients, as well as external observers, may have a tendency to overestimate impairments of consciousness during the seizures. PMID:21447903

The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection

PubMed Central

Latini, Francesco; Hjortberg, Mats; Aldskogius, Håkan; Ryttlefors, Mats

2015-01-01

The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity. PMID:26063964

Drug monitoring: simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydroxycarbazepine, and zonisamide by HPLC-UV and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam

PubMed Central

Greiner-Sosanko, Elizabeth; Giannoutsos, Spiros; Lower, Darla R.; Virji, Mohamed A.; Krasowski, Matthew D.

2008-01-01

A high-performance liquid chromatography (HPLC) assay using ultraviolet detection is described for the simultaneous measurement of the newer generation anti-epileptic medications lamotrigine, oxcarbazepine (parent drug and active metabolite 10-hydroxycarbazepine), and zonisamide. Detection of all four compounds can be done at 230 nm; however, there is a potential interference with zonisamide in patients on clonazepam therapy. Therefore, the method uses dual wavelength detection: 230 nm for oxcarbazepine and 10-hydroxycarbazepine and 270 nm for lamotrigine and zonisamide. In addition, a simple gas chromatography method using a nitrogen-phosphorus detector is described for measurement of levetiracetam, another of the recently approved anti-epileptic medications. For both methods, limits of quantitation, linearities, accuracies, and imprecisions cover the therapeutic range for drug monitoring of patients. A wide variety of clinical drugs, including other anti-epileptic drugs, do not interfere with these assays. These procedures would be of special interest to clinical laboratories, particularly due to the limited availability of immunoassays for newer generation anti-epileptic medications and that therapeutic uses of these drugs are expanding beyond epilepsy to other neurologic and psychiatric disorders. PMID:17988451

Multimodal investigation of epileptic networks: The case of insular cortex epilepsy.

PubMed

Zerouali, Y; Ghaziri, J; Nguyen, D K

2016-01-01

The insula is a deep cortical structure sharing extensive synaptic connections with a variety of brain regions, including several frontal, temporal, and parietal structures. The identification of the insular connectivity network is obviously valuable for understanding a number of cognitive processes, but also for understanding epilepsy since insular seizures involve a number of remote brain regions. Ultimately, knowledge of the structure and causal relationships within the epileptic networks associated with insular cortex epilepsy can offer deeper insights into this relatively neglected type of epilepsy enabling the refining of the clinical approach in managing patients affected by it. In the present chapter, we first review the multimodal noninvasive tests performed during the presurgical evaluation of epileptic patients with drug refractory focal epilepsy, with particular emphasis on their value for the detection of insular cortex epilepsy. Second, we review the emerging multimodal investigation techniques in the field of epilepsy, that aim to (1) enhance the detection of insular cortex epilepsy and (2) unveil the architecture and causal relationships within epileptic networks. We summarize the results of these approaches with emphasis on the specific case of insular cortex epilepsy. © 2016 Elsevier B.V. All rights reserved.

Health related quality of life in patients admitted for video-electroencephalography monitoring diagnosed with epilepsy or psychogenic non-epileptic seizures.

PubMed

Yerdelen, Deniz; Altintas, Ebru

2016-01-01

To determine the health related quality of life (HRQOL) in patients with epilepsy or psychogenic non-epileptic seizures (PNES). This cross-sectional study was carried out between December 2010 and December 2014 in the Department of Neurology and Psychiatry, Faculty of Medicine, Baskent University, Adana, Turkey. Patients who were admitted for video-electroencephalography monitoring and diagnosed of epileptic seizures or PNES were asked to complete a questionnaire from the World Health Organization Quality of Life, and psychiatric comorbidities were diagnosed using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. Patients with epilepsy and PNES were found to have similar HRQOL in physical, psychological, social, and environmental domains. However, the percentage of comorbid psychiatric disorders were higher in patients with PNES than patients with epilepsy. Patients with epilepsy and PNES have similar HRQOL, and PNES are resistant to the standard medical therapies used for the treatment of epileptic seizures. The direct lifetime cost of undiagnosed PNES may be of equal with intractable epilepsy. A better understanding of the impact of PNES manifestations and epilepsy would help to provide appropriate clinical, psychological and social care.

The dynamics of human cognition: Increasing global integration coupled with decreasing segregation found using iEEG.

PubMed

Cruzat, Josephine; Deco, Gustavo; Tauste-Campo, Adrià; Principe, Alessandro; Costa, Albert; Kringelbach, Morten L; Rocamora, Rodrigo

2018-05-15

Cognitive processing requires the ability to flexibly integrate and process information across large brain networks. How do brain networks dynamically reorganize to allow broad communication between many different brain regions in order to integrate information? We record neural activity from 12 epileptic patients using intracranial EEG while performing three cognitive tasks. We assess how the functional connectivity between different brain areas changes to facilitate communication across them. At the topological level, this facilitation is characterized by measures of integration and segregation. Across all patients, we found significant increases in integration and decreases in segregation during cognitive processing, especially in the gamma band (50-90 Hz). We also found higher levels of global synchronization and functional connectivity during task execution, again particularly in the gamma band. More importantly, functional connectivity modulations were not caused by changes in the level of the underlying oscillations. Instead, these modulations were caused by a rearrangement of the mutual synchronization between the different nodes as proposed by the "Communication Through Coherence" Theory. Copyright © 2018 Elsevier Inc. All rights reserved.

Electrical Cerebral Stimulation Modifies Inhibitory Systems

NASA Astrophysics Data System (ADS)

Cuéllar-Herrera, M.; Rocha, L.

2003-09-01

Electrical stimulation of the nervous tissue has been proposed as a method to treat some neurological disorders, such as epilepsy. Epileptic seizures result from excessive, synchronous, abnormal firing patterns of neurons that are located predominantly in the cerebral cortex. Many people with epilepsy continue presenting seizures even though they are under regimens of antiepileptic medications. An alternative therapy for treatment resistant epilepsy is cerebral electrical stimulation. The present study is focused to review the effects of different types of electrical stimulation and specifically changes in amino acids.

Epileptogenicity and pathology - Under consideration of ablative approaches.

PubMed

Stefan, H; Schmitt, F C

2018-05-01

Besides resective epilepsy surgery, minimally invasive ablation using new diagnostic and therapeutic techniques recently became available. Optimal diagnostic approaches for these treatment options are discussed. The pathophysiology of epileptogenic networks differs depending on the lesion-types and location, requiring a differential use of non-invasive or invasive functional studies. In addition to the definition of epileptogenic zones, a challenge for pre-surgical investigation is the determination of three-dimensional epileptic networks to be removed. Copyright © 2018. Published by Elsevier B.V.

A case study on Discrete Wavelet Transform based Hurst exponent for epilepsy detection.

PubMed

Madan, Saiby; Srivastava, Kajri; Sharmila, A; Mahalakshmi, P

2018-01-01

Epileptic seizures are manifestations of epilepsy. Careful analysis of EEG records can provide valuable insight and improved understanding of the mechanism causing epileptic disorders. The detection of epileptic form discharges in EEG is an important component in the diagnosis of epilepsy. As EEG signals are non-stationary, the conventional frequency and time domain analysis does not provide better accuracy. So, in this work an attempt has been made to provide an overview of the determination of epilepsy by implementation of Hurst exponent (HE)-based discrete wavelet transform techniques for feature extraction from EEG data sets obtained during ictal and pre ictal stages of affected person and finally classifying EEG signals using SVM and KNN Classifiers. The The highest accuracy of 99% is obtained using SVM.

Stimulus driver for epilepsy seizure suppression with adaptive loading impedance

NASA Astrophysics Data System (ADS)

Ker, Ming-Dou; Lin, Chun-Yu; Chen, Wei-Ling

2011-10-01

A stimulus driver circuit for a micro-stimulator used in an implantable device is presented in this paper. For epileptic seizure control, the target of the driver was to output 30 µA stimulus currents when the electrode impedance varied between 20 and 200 kΩ. The driver, which consisted of the output stage, control block and adaptor, was integrated in a single chip. The averaged power consumption of the stimulus driver was 0.24-0.56 mW at 800 Hz stimulation rate. Fabricated in a 0.35 µm 3.3 V/24 V CMOS process and applied to a closed-loop epileptic seizure monitoring and controlling system, the proposed design has been successfully verified in the experimental results of Long-Evans rats with epileptic seizures.

Differential diagnosis of epileptic seizures in infancy including the neonatal period.

PubMed

Cross, J Helen

2013-08-01

It is important to accurately diagnose epileptic seizures in early life to optimise management and prognosis. Conversely, however, many different movements and behaviours may manifest in the neonatal period and infancy that may not have at their root cause a change in electrical activity of the brain. It is important to distinguish them from epileptic seizures to avoid over- and inappropriate treatment. Some are physiological in the normal infant, such as neonatal tremor, benign neonatal sleep myoclonus, and shuddering attacks, whereas others may herald alternative rare neurological diagnoses with differing prognoses such as hyperekplexia, paroxysmal extreme pain disorder and alternating hemiplegia of childhood. Here are highlighted the key clinical features that distinguish some of these disorders, their management and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Piriform Cortex and Human Focal Epilepsy

PubMed Central

Vaughan, David N.; Jackson, Graeme D.

2014-01-01

It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. PMID:25538678

[Analysis of gene mutation of early onset epileptic spasm with unknown reason].

PubMed

Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

2017-11-02

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks). Among them, five cases had no effect and two cases were seizure free recently. A case with GABRB3 (C.905A>G) had seizure controlled for 3 mouths. A case with ARX (C.700G>A) had seizure controlled for 6 mouths. Conclusion: The early onset epileptic spasm with unknown reason is highly related to genetic disorders. A variety of genetic mutations, especially new mutations were found. Genetic heterogeneity of epileptic spasm is obvious.

In Utero Administration of Drugs Targeting Microglia Improves the Neurodevelopmental Outcome Following Cytomegalovirus Infection of the Rat Fetal Brain

PubMed Central

Cloarec, Robin; Bauer, Sylvian; Teissier, Natacha; Schaller, Fabienne; Luche, Hervé; Courtens, Sandra; Salmi, Manal; Pauly, Vanessa; Bois, Emilie; Pallesi-Pocachard, Emilie; Buhler, Emmanuelle; Michel, François J.; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N.; Bruneau, Nadine; Szepetowski, Pierre

2018-01-01

Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain. PMID:29559892

Early Detection of Human Focal Seizures Based on Cortical Multiunit Activity

PubMed Central

Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

2014-01-01

Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing (spike counts) applied to the 300 Hz – 6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 ± 2.27 sec (mean ± SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. PMID:25571313

Activity of hippocampal, amygdala, and neocortex during the Rey auditory verbal learning test: an event-related potential study in epileptic patients.

PubMed

Babiloni, Claudio; Vecchio, Fabrizio; Mirabella, Giovanni; Sebastiano, Fabio; Di Gennaro, Giancarlo; Quarato, Pier P; Buffo, Paola; Esposito, Vincenzo; Manfredi, Mario; Cantore, Giampaolo; Eusebi, Fabrizio

2010-08-01

Previous evidence in epileptic subjects has shown that theta (about 4-7Hz) and gamma rhythms (about 40-45Hz) of hippocampus, amygdala, and neocortex were temporally synchronized during the listening of repeated words successfully remembered (Babiloni et al., 2009). Here we re-analyzed those electroencephalographic (EEG) data to test whether a parallel increase in amplitude of late positive event-related potentials takes place. Intracerebral electroencephalographic (EEG) activity had been recorded in five subjects with drug-resistant temporal lobe epilepsy, undergoing pre-surgical evaluation. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of the Rey auditory verbal learning test (RAVLT). They heard the same list of 15 common words for five times. Each time, immediately after the listening of the list, the subjects were required to repeat as many words as they could recall. We found that late positive event-related potentials (ERPs) peaking at about 350ms post-stimulus in amygdala, hippocampus, and occipital-temporal cortex had a higher amplitude during the listening of the repeated words that were subsequently recalled than for those that were not recalled. Late positive ERPs reflect a functional mechanism implemented in a human brain network spanning amygdala, hippocampus, and occipital-temporal cortex which is at the basis of the memorization processes of verbal materials. This ERP component is a promising neuromarker of successful memorization of repeated words in humans. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Short-term depression of gap junctional coupling in reticular thalamic neurons of absence epileptic rats.

PubMed

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 gap junctional blockers into RTN of GAERS in vivo resulted in a decrease of spike wave discharge (SWD) activity. Repeated activation results in a short-term depression (STD) of gap junctional coupling in RTN neurons of GAERS, depending on intracellular Ca(2+) mechanisms in the activated cell. As blockage of gap junctions in vivo results in a decrease of SWD activity, the STD observed in GAERS is considered a compensatory mechanism, aimed to dampen SWD activity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Spatio-temporal analysis of brain electrical activity in epilepsy based on cellular nonlinear networks

NASA Astrophysics Data System (ADS)

Gollas, Frank; Tetzlaff, Ronald

2009-05-01

Epilepsy is the most common chronic disorder of the nervous system. Generally, epileptic seizures appear without foregoing sign or warning. The problem of detecting a possible pre-seizure state in epilepsy from EEG signals has been addressed by many authors over the past decades. Different approaches of time series analysis of brain electrical activity already are providing valuable insights into the underlying complex dynamics. But the main goal the identification of an impending epileptic seizure with a sufficient specificity and reliability, has not been achieved up to now. An algorithm for a reliable, automated prediction of epileptic seizures would enable the realization of implantable seizure warning devices, which could provide valuable information to the patient and time/event specific drug delivery or possibly a direct electrical nerve stimulation. Cellular Nonlinear Networks (CNN) are promising candidates for future seizure warning devices. CNN are characterized by local couplings of comparatively simple dynamical systems. With this property these networks are well suited to be realized as highly parallel, analog computer chips. Today available CNN hardware realizations exhibit a processing speed in the range of TeraOps combined with low power consumption. In this contribution new algorithms based on the spatio-temporal dynamics of CNN are considered in order to analyze intracranial EEG signals and thus taking into account mutual dependencies between neighboring regions of the brain. In an identification procedure Reaction-Diffusion CNN (RD-CNN) are determined for short segments of brain electrical activity, by means of a supervised parameter optimization. RD-CNN are deduced from Reaction-Diffusion Systems, which usually are applied to investigate complex phenomena like nonlinear wave propagation or pattern formation. The Local Activity Theory provides a necessary condition for emergent behavior in RD-CNN. In comparison linear spatio-temporal autoregressive filter models are considered, for a prediction of EEG signal values. Thus Signal features values for successive, short, quasi stationary segments of brain electrical activity can be obtained, with the objective of detecting distinct changes prior to impending epileptic seizures. Furthermore long term recordings gained during presurgical diagnostics in temporal lobe epilepsy are analyzed and the predictive performance of the extracted features is evaluated statistically. Therefore a Receiver Operating Characteristic analysis is considered, assessing the distinguishability between distributions of supposed preictal and interictal periods.

The Persistence of Erroneous Familiarity in an Epileptic Male: Challenging Perceptual Theories of Deja Vu Activation

ERIC Educational Resources Information Center

O'Connor, Akira R.; Moulin, Christopher J. A.

2008-01-01

We report the case of a 39-year-old, temporal lobe epileptic male, MH. Prior to complex partial seizure, experienced up to three times a day, MH often experiences an aura experienced as a persistent sensation of deja vu. Data-driven theories of deja vu formation suggest that partial familiarity for the perceived stimulus is responsible for the…

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.

Epileptic seizure prediction by non-linear methods

DOEpatents

Hively, Lee M.; Clapp, Ned E.; Daw, C. Stuart; Lawkins, William F.

1999-01-01

Methods and apparatus for automatically predicting epileptic seizures monitor and analyze brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis tools; obtaining time serial trends in the nonlinear measures; comparison of the trend to known seizure predictors; and providing notification that a seizure is forthcoming.

A Study into the Possible Link between Anti-Epileptic Drugs and the Risk of Fractures in Muckamore Abbey Hospital.

ERIC Educational Resources Information Center

Tohill, Carmel

1997-01-01

A study investigated whether the effects of anti-epileptic drugs were (carbamazepine, phenobarbitone, and phenytoin) related, to the incidence of fractures in 85 Irish patients. If patients were only on one antiepileptic drug, there appeared to be no correlation; however, if patients were taking a combination of three drugs, they were more likely…

Eye-closure-triggered paroxysmal activity and cognitive impairment: a case report.

PubMed

Termine, Cristiano; Rubboli, Guido; Veggiotti, Pierangelo

2006-01-01

To study the neuropsychological status of an epileptic patient presenting with epileptic activity triggered by eye closure in a 14-year follow-up period. The patient was studied at 12 and 26 years of age; during this period he underwent periodical clinical evaluations and EEG investigations; brain magnetic resonance imaging (MRI) was performed at 12 years of age. A neuropsychological assessment was carried out both at 12 years of age (T0) and at 26 years of age. At T0 and T1, neuropsychological tests (digits and words span, graphoestesia, reactions time to auditory stimuli, sentences repetition, words repetition, digital gnosis, backward counting [i.e.,100-0]) were performed during video-EEG monitoring either with eyes closed or with eyes open, to evaluate possible transitory effects related to ongoing epileptic activity. Moreover, at T0 the patient underwent Wechsler Intelligence Scale for Children-Revised, and at T1 to Wechsler Adult Intelligence Scale-Revised. EEG recordings showed continuous epileptic activity triggered by eye closure, disappearing only with eyes opening, both at T0 and T1 (in this latter case, anteriorly predominant). The results of neuropsychological assessment during eyes closed as compared to performances with eyes open did not show significant differences, at T0 as well as at T1. Wechsler Intelligence scales showed a deterioration of performances at T1 with respect to T0; in addition, at T1, attention and short-term memory abnormalities, impairment in facial recognition and block design, and defective results in Continuous Performance Test and Wisconsin Card Sorting Test were observed. Lack of differences between the results of neuropsychological tests performed with eyes closed as compared to the eyes open condition suggests that in our patient epileptic activity did not cause transitory cognitive abnormalities. Deterioration of Wechsler Intelligence Scales in the follow-up period might be interpreted as the result of a disruption of cognitive processes possibly related to the persistence of a continuous epileptic activity during eye closure over the years. We speculate whether a dysfunction in posterior cortical areas involved in visual processing might be related to the impairment in face recognition and block design tests as well to eye closure sensitivity.

Misdiagnosis of gastroesophageal reflux disease as epileptic seizures in children.

PubMed

Bayram, Ayşe Kaçar; Canpolat, Mehmet; Karacabey, Neslihan; Gumus, Hakan; Kumandas, Sefer; Doğanay, Selim; Arslan, Duran; Per, Hüseyin

2016-03-01

Gastroesophageal reflux disease (GERD) can mimic epileptic seizure, and may be misdiagnosed as epilepsy. On the other hand, GERD can be more commonly seen in children with neurological disorders such as cerebral palsy (CP); this co-incidence may complicate the management of patients by mimicking refractory seizures. The purpose of our study was to evaluate the clinical features, definite diagnoses and treatment approaches of the patients with clinically suspected GERD who were referred to the division of pediatric neurology with a suspected diagnosis of epileptic seizure. We also aimed to investigate the occurrence of GERD in children with epilepsy and/or CP. Fifty-seven children who had a final diagnosis of GERD but were initially suspected of having epileptic seizures were assessed prospectively. All patients were assigned to 3 groups according to definite diagnoses as follows: patients with only GERD who were misdiagnosed as having epileptic seizure (group 1: n=16; 28.1%), those with comorbidity of epilepsy and GERD (group 2: n=21; 36.8%), and those with the coexistence of GERD with epilepsy and CP (group 3: n=20; 35.1%). Five patients (8.8%) did not respond to anti-reflux treatment and laparoscopic reflux surgery was performed. The positive effect of GERD therapy on paroxysmal nonepileptic events was observed in 51/57 (89.5%) patients. GERD is one of the important causes of paroxysmal nonepileptic events. In addition, GERD must be kept in mind at the initial diagnosis and also in the long-term management of patients with neurological disorders such as epilepsy and CP. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

'Epileptic', 'epileptic person' or 'person with epilepsy'? Bringing quantitative and qualitative evidence on the views of UK patients and carers to the terminology debate.

PubMed

Noble, Adam J; Robinson, Abbey; Snape, Darlene; Marson, Anthony G

2017-02-01

How to refer to someone with epilepsy is a divisive topic. Arguments for and against different approaches, including traditional adjective labels, disability-first labels, and person-first terms have been presented. The preferences of those with epilepsy and their family and friends have, though, never been determined. This study provides this information for the first time. Via epilepsy interest groups and organizations in the UK and Republic of Ireland, 638 patients and 333 significant others completed an online survey. Three distinct phrases were presented: "They're epileptic" (traditional label), "They're an epileptic person" (disability-first) and "That person has epilepsy" (person-first). Participants identified which they preferred and explained their choices. Patients' median age was 39, with 69% having experienced seizures in the prior 12months. Significant others were typically parents. Most (86.7%) patients and significant others (93.4%) favored the person-first term. Traditional and disability-first terms were "Disliked"/"Strongly disliked". Regression found it was not possible to reliably distinguish between participants favoring the different terms on the basis of demographics. Qualitative analysis of answers to open-ended questions, however, revealed most favored person-first terminology as by not including the word 'epileptic' and by affirming personhood before disability, it was felt to less likely restrict a listener's expectations or evoke the condition's negative association. It was also considered to suggest the person being referred to might have some mastery over their condition. The findings indicate consensus amongst these key stakeholders others for the use of person-first terminology in English. A truly informed debate on the topic can now begin. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Pregestational stress attenuated fertility rate in dams and increased seizure susceptibility in offspring.

PubMed

Mahmoodkhani, Maryam; Saboory, Ehsan; Roshan-Milani, Shiva; Azizi, Negar; Karimipour, Mojtaba; Rasmi, Yosef; Gholinejad, Zafar

2018-02-01

Many studies have found that stress during pregnancy is linked to an increased incidence of epileptic behaviors and reproductive disorders. However, few works have investigated the effect of pregestational stress on seizure susceptibility in the offspring. We investigated the effect of pregestational stress on epileptic behaviors in the offspring as well as fertility rate in dams. The male and female rats were randomly divided into four groups to form a combination of control and stressed groups for each sex. The rats were subjected to predatory stress (exposed to a cat) twice per day for 50 (male) and 15 (female) consecutive days. At the end of the stress procedure, the rats were coupled as follows: both male and female control (M C -F C ), male stressed/female control (M S -F C ), male control/female stressed (M C -F S ), and both male and female stressed (M S -F S ). Then, the puppies born from these groups were counted and evaluated for pentylentetrazole (PTZ)-induced seizure. There was no significant difference between the male and female pups in each identical group in terms of litter size and epileptic behaviors, except duration of tail rigidity and duration of immobility. The total score of seizure increased in all the stressed groups, but more severely in the M S -F S group. However, the onset of the first epileptic behavior and tonic-clonic seizure significantly decreased in the stressed groups. Moreover, fertility rate significantly decreased in the stressed groups compared with the control group, but there was no significant difference in terms of litter size between the groups. These data revealed the impact of pregestational stress during spermatogenesis and oogenesis on fertility rate in dams and epileptic behaviors in the offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazol-induced epileptic behaviors in infant and prepubertal rats.

PubMed

Ebrahimi, Loghman; Saboory, Ehsan; Roshan-Milani, Shiva; Hashemi, Paria

2014-09-01

Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. Many reports have shown an interaction between morphine- and stress-induced behavioral changes in adult rats. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylentetrazole (PTZ)-induced epileptic behaviors was investigated in rat offspring to address effect of the interaction between morphine and stress. Pregnant rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, the rats were placed in 25 °C water on 17-19 days of pregnancy. In the morphine/saline group, the rats received morphine/saline on the same days. In the morphine/saline-stressed group, they were exposed to stress and received morphine/saline simultaneously. On postnatal day 15 (P15), blood samples were collected to determine corticosterone (COS) level. On P15 and P25, PTZ was injected to the rest of pups to induce seizure. Then, epileptic behaviors of each rat were individually observed. Latency of tonic-colonic seizures decreased in control-morphine and stressed-saline groups while increasing in stressed-morphine rats compared to control-saline group on P15. Duration of tonic-colonic seizures significantly increased in control-morphine and stressed-saline rats compared to stressed-morphine and control-saline rats on P15, but not P25. COS levels increased in stressed-saline group but decreased in control-morphine group compared to control-saline rats. Body weight was significantly higher in morphine groups than saline treated rats. Prenatal exposure to forced-swim stress potentiated PTZ-induced seizure in the offspring rats. Co-administration of morphine attenuated effect of stress on body weight, COS levels, and epileptic behaviors. © 2014 Wiley Periodicals, Inc.

The role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures.

PubMed

Nass, Robert D; Sassen, Robert; Elger, Christian E; Surges, Rainer

2017-04-01

Epileptic seizures (ES) lead to alterations in the blood laboratory values and reflect changes in different organ systems. Here, we review the diagnostic and prognostic value of various blood laboratory values within the context of epilepsy. Narrative review and literature search on PubMed using the term, "seizure" and various laboratory values. Laboratory markers can help clinicians determine whether an unwitnessed event was more likely to be epileptic or non-epileptic. Prolactin testing helps differentiate ES from psychogenic non-epileptic seizures (PNES) in adults and adolescents, and is associated with high specificity and moderate sensitivity. Elevations in the creatine kinase (CK) levels are common after generalized tonic-clonic seizures (GTCS) and display high specificity and moderate sensitivity. Metabolic markers such as ammonia and lactate may have diagnostic potential for postictal blood tests. Analyzing blood postictally is important for identifying the cause of the symptomatic seizures due to endocrine, metabolic, toxic or infectious etiologies. Finally, laboratory analyses are used for identifying patients who are at risk for developing rare, threatening complications such as rhabdomyolysis, acute renal failure (ARF) or cardiomyopathy. Presently, no postictal laboratory values can definitively prove or rule out the diagnosis of an epileptic seizure. For seizures with unknown causes, simple blood tests can be a valuable aid for quickly defining the etiology, particularly with certain metabolic and toxic encephalopathies. For this reason, CK, electrolytes, creatinine, liver and renal function tests should be measured on at least one occasion. Further research is needed in order to identify new biomarkers that improve the diagnosis and prognosis of seizures and seizure-related complications. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Paroxysmal non-epileptic events in infants and toddlers: A phenomenologic analysis.

PubMed

Chen, Li; Knight, Elia M Pestana; Tuxhorn, Ingrid; Shahid, Asim; Lüders, Hans O

2015-06-01

The aim of this study was to analyze in detail the clinical phenomenology of paroxysmal non-epileptic events (PNEE) in infants and toddlers. We studied all children aged ≤2 years who were diagnosed with PNEE based on video-electroencephalographic (VEEG) recordings. We analyzed the following four clinical domains of each clinical event: (i) motor manifestations (body/limb jerking, complex motor, and asymmetric limb posturing); (ii) oral/vocal (crying, vocalization, sighing); (iii) behavioral change (arrest of activity, staring); (iv) and autonomic (facial flushing, breath holding). Thirty-one of 81 (38.3%) infants and toddlers had 38 PNEE recorded during the study period (12 girls and 19 boys, mean age 10.5 months). The predominant clinical features were as follows: motor in 26/38 events, oral/verbal in 14/38 events, behavioral in 11/38 events, and autonomic in 8/38 events. Epileptic seizures and PNEE coexisted in four children (12.9%). Seventeen children (54.8%) had one or more risk factors suggestive of epilepsy. Twelve children (38.7%) had a normal neurologic examination, 10 (32.3%) had developmental delay, and eight (25.8%) had a family history of epilepsy or seizures. VEEG recorded PNEE in nearly 40% of 81 infants and toddlers referred for unclear paroxysmal events in our cohort. Non-epileptic staring spells and benign sleep myoclonus were the most common events recorded, followed by shuddering attacks and infantile masturbation. In addition, greater than one-half of the infants and toddlers had risk factors, raising a concern for epilepsy in the family and prompting the VEEG evaluation, suggesting that paroxysmal non-epileptic seizures may frequently coexist in young children with epilepsy. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.

PubMed

Sugaya, Yuki; Kano, Masanobu

2018-05-08

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.

Comparative case-control study of homocysteine, vitamin B12, and folic acid levels in patients with epilepsy.

PubMed

Pulido Fontes, L; Pulido Fontes, M; Quesada Jiménez, P; Muruzabal Pérez, J; Mendioroz Iriarte, M

2017-09-01

Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk. We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B 12 . Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05). Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Alpha, delta and theta rhythms in a neural net model. Comparison with MEG data.

PubMed

Kotini, A; Anninos, P

2016-01-07

The aim of this study is to provide information regarding the comparison of a neural model to MEG measurements. Our study population consisted of 10 epileptic patients and 10 normal subjects. The epileptic patients had high MEG amplitudes characterized with θ (4-7 Hz) or δ (2-3 Hz) rhythms and absence of α-rhythm (8-13 Hz). The statistical analysis of such activities corresponded to Poisson distribution. Conversely, the MEG from normal subjects had low amplitudes, higher frequencies and presence of α-rhythm (8-13 Hz). Such activities were not synchronized and their distributions were Gauss. These findings were in agreement with our theoretical neural model. The comparison of the neural network with MEG data provides information about the status of brain function in epileptic and normal states. Copyright © 2015 Elsevier Ltd. All rights reserved.

Which Brain Regions are Important for Seizure Dynamics in Epileptic Networks? Influence of Link Identification and EEG Recording Montage on Node Centralities.

PubMed

Geier, Christian; Lehnertz, Klaus

2017-02-01

Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics.

[Ictal Speech Manifesting as Sleep Talking: A Case Report].

PubMed

Suzuki, Takehiro; Kakisaka, Yosuke; Kitazawa, Yu; Jin, Kazutaka; Sato, Shiho; Iwasaki, Masaki; Fujikawa, Mayu; Nishio, Yoshiyuki; Kanno, Akitake; Nakasato, Nobukazu

2017-02-01

We present a 28-year-old female patient whose epilepsy started at the age of 19. MRI showed right perisylvian polymicrogyria. She exhibited various seizure symptoms, such as somatosensory aura involving the left leg, dyscognitive seizures, and amnesic seizures. Her mother indicated that the patient sometimes had "sleep talking", which was associated with presence of epileptic seizures of the next day. Long-term video electroencephalography (EEG) revealed that her episodes of "sleep talking" were epileptic events, specifically ictal speech, originating in the right hemisphere. The present case demonstrates the importance of considering "sleep talk" as an epileptic symptom. Careful history taking is fundamental to carry patients with possibly pathological "sleep talk" to the long-term video EEG, which will contribute correct diagnosis and treatment. (Received August 16, 2016; Accepted September 9, 2016; Published February 1, 2017).

Effect of conductor geometry on source localization: Implications for epilepsy studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlitt, H.; Heller, L.; Best, E.

1994-07-01

We shall discuss the effects of conductor geometry on source localization for applications in epilepsy studies. The most popular conductor model for clinical MEG studies is a homogeneous sphere. However, several studies have indicated that a sphere is a poor model for the head when the sources are deep, as is the case for epileptic foci in the mesial temporal lobe. We believe that replacing the spherical model with a more realistic one in the inverse fitting procedure will improve the accuracy of localizing epileptic sources. In order to include a realistic head model in the inverse problem, we mustmore » first solve the forward problem for the realistic conductor geometry. We create a conductor geometry model from MR images, and then solve the forward problem via a boundary integral equation for the electric potential due to a specified primary source. One the electric potential is known, the magnetic field can be calculated directly. The most time-intensive part of the problem is generating the conductor model; fortunately, this needs to be done only once for each patient. It takes little time to change the primary current and calculate a new magnetic field for use in the inverse fitting procedure. We present the results of a series of computer simulations in which we investigate the localization accuracy due to replacing the spherical model with the realistic head model in the inverse fitting procedure. The data to be fit consist of a computer generated magnetic field due to a known current dipole in a realistic head model, with added noise. We compare the localization errors when this field is fit using a spherical model to the fit using a realistic head model. Using a spherical model is comparable to what is usually done when localizing epileptic sources in humans, where the conductor model used in the inverse fitting procedure does not correspond to the actual head.« less

Increased hair cortisol and antecedent somatic complaints in children with a first epileptic seizure.

PubMed

Stavropoulos, Ioannis; Pervanidou, Panagiota; Gnardellis, Charalampos; Loli, Nomiki; Theodorou, Virginia; Mantzou, Aimilia; Soukou, Faye; Sinani, Olga; Chrousos, George P

2017-03-01

Stress is the most frequent seizure-precipitating factor reported by patients with epilepsy, while stressful life events may increase seizure susceptibility in humans. In this study, we investigated the relations between both biological and behavioral measures of stress in children with a first epileptic seizure (hereafter called seizure). We hypothesized that hair cortisol, a biomarker of chronic stress reflecting approximately 3months of preceding exposure, might be increased in children with a first seizure. We also employed standardized questionnaires to examine presence of stress-related behavioral markers. This was a cross-sectional clinical study investigating stress-related parameters in children with a first seizure (First Epileptic Seizure Group (FESG), n=22) in comparison to healthy children without seizures (Control Group, n=29). Within 24h after a first seizure, hair samples were collected from children for the determination of cortisol. In parallel, perceived stress and anxiety and depressive symptoms were examined with appropriate self- and parent-completed questionnaires, and history of stressful life events during the past year was recorded. Emotional and behavioral problems were also assessed by parent-reported validated and widely-used questionnaires. Higher hair cortisol measurements were observed in the FESG than control children (7.5 versus 5.0pg/mg respectively, p=0.001). The former were more likely to complain of somatic problems than the latter (59.8 vs. 55.4 according to DSM-oriented Scale, p=0.021); however, there were no differences in perceived stress and anxiety or depressive symptoms between the two groups. Using ROC analysis of hair cortisol measurements for predicting disease status, the maximum sensitivity and specificity were observed for a cut-off point of 5.25pg/mg. Increased hair cortisol indicates chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis prior to the first seizure. This might have contributed to the epileptogenesis process and may help explain the higher incidence of antecedent somatic complaints in the first seizure group. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior of Rats.

PubMed

A, Mahmoudi; M B, Shojaeifard; S, Nematollahii; S M J, Mortazavi; A R, Mehdizadeh

2018-06-01

Electromagnetic fields (EMF) with different intensities are widely used at home, offices and public places.Today, there is a growing global concern about the effects of human exposure to EMFs. Epilepsy is one of the most common chronic neurological diseases, affecting 50 million people of all ages worldwide. We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic behavior of rats. 147 male rats, weighing 200-250 g, were divided into seven groups; negative control (no intervention), sham 1(distilled water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi-Fi "off"), sham 2 (distilled water + Wi-Fi "off"), sham 3 (distilled water + Wi-Fi "on"), and intervention group 2 (PTZ + Wi-Fi "on"). The rats were exposed to Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive behaviors of rats were monitored and scored based on the intensity and type by measuring latency/threshold time, number of convulsions, sum of scores and durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann-Whitney U-tests were used to analyze the data. Convulsion was observed in interventions Group 4 and Group 7, and positive control. The mean number of events, and sum of scores were significantly different in intervention 2 than other two groups. However, the differences in mean threshold, mean sum of durations and " time to show convulsion with score 6 " were not statistically significant (P>0.05). Due to limitations of our study including the sample size, these findings should be interpreted with caution. In this study, exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the epileptic behaviour of rats. More experiments are needed to verify if these exposures can be used as a therapeutic approach for amelioration of seizures in epilepsy.

Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior of Rats

PubMed Central

A., Mahmoudi; M.B., Shojaeifard; S., Nematollahii; S.M.J., Mortazavi; A.R., Mehdizadeh

2018-01-01

Background: Electromagnetic fields (EMF) with different intensities are widely used at home, offices and public places.Today, there is a growing global concern about the effects of human exposure to EMFs. Epilepsy is one of the most common chronic neurological diseases, affecting 50 million people of all ages worldwide. We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic behavior of rats. Materials and Methods: 147 male rats, weighing 200-250 g, were divided into seven groups; negative control (no intervention), sham 1(distilled water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi-Fi “off”), sham 2 (distilled water + Wi-Fi “off”), sham 3 (distilled water + Wi-Fi “on”), and intervention group 2 (PTZ + Wi-Fi “on”). The rats were exposed to Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive behaviors of rats were monitored and scored based on the intensity and type by measuring latency/threshold time, number of convulsions, sum of scores and durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann-Whitney U-tests were used to analyze the data. Results: Convulsion was observed in interventions Group 4 and Group 7, and positive control. The mean number of events, and sum of scores were significantly different in intervention 2 than other two groups. However, the differences in mean threshold, mean sum of durations and “ time to show convulsion with score 6 ” were not statistically significant (P>0.05). Conclusion: Due to limitations of our study including the sample size, these findings should be interpreted with caution. In this study, exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the epileptic behaviour of rats. More experiments are needed to verify if these exposures can be used as a therapeutic approach for amelioration of seizures in epilepsy. PMID:29951445

Postictal aphasia and paresis: a clinical and intracerebral EEG study.

PubMed

Adam, C; Adam, C; Rouleau, I; Saint-Hilaire, J M

2000-02-01

We examined the lateralizing value of postictal language and motor deficits and studied their underlying mechanisms. The total sample consisted of 35 patients (26 temporals, 8 frontals, 1 parietal) with a good postsurgical outcome (Engel's class I and II). Postictal examination was blindly reviewed on videotapes. In 15 cases (29 seizures), postictal language manifestations were analyzed in relation with the diffusion of the epileptic discharge recorded by intracerebral EEG. Language dominance was determined by the intracarotid amobarbital test. Postictal aphasia was observed only when (1) seizure originated in the dominant hemisphere and (2) ictal activity spread to language areas (Wernicke and/or Broca areas). When the epileptic focus was in the nondominant hemisphere, no postictal aphasia was observed even if there was secondary generalization of ictal activity affecting the language areas of the dominant hemisphere. Postictal motor deficits also had a strong lateralizing value even when seizures were secondarily generalized. Postictal aphasia in temporal epilepsies and postical motor deficits in temporal and extra temporal epilepsies provided excellent lateralizing information. Postictal deficits appear to be the result of inhibitory mechanisms induced by previous ictal activity of the structures related to these functions.

Cerebral hemodynamic responses to seizure in the mouse brain: simultaneous near-infrared spectroscopy-electroencephalography study

NASA Astrophysics Data System (ADS)

Lee, Seungduk; Lee, Mina; Koh, Dalkwon; Kim, Beop-Min; Choi, Jee Hyun

2010-05-01

We applied near-infrared spectroscopy (NIRS) and electroencephalography (EEG) simultaneously on the mouse brain and investigated the hemodynamic response to epileptic episodes under pharmacologically driven seizure. γ-butyrolactone (GBL) and 4-aminopyridine (4-AP) were applied to induce absence and tonic-clonic seizures, respectively. The epileptic episodes were identified from the single-channel EEG, and the corresponding hemodynamic changes in different regions of the brain were characterized by multichannel frequency-domain NIRS. Our results are the following: (i) the oxyhemoglobin level increases in the case of GBL-treated mice but not 4-AP-treated mice compared to the predrug state; (ii) the dominant response to each absence seizure is a decrease in deoxyhemolobin; (iii) the phase shift between oxy- and deoxyhemoglobin reduces in GBL-treated mice but no 4-AP-treated mice; and (iv) the spatial correlation of hemodynamics increased significantly in 4-AP-treated mice but not in GBL-treated mice. Our results shows that spatiotemporal tracking of cerebral hemodynamics using NIRS can be successfully applied to the mouse brain in conjunction with electrophysiological recording, which will support the study of molecular, cellular, and network origin of neurovascular coupling in vivo.

Unsupervised EEG analysis for automated epileptic seizure detection

NASA Astrophysics Data System (ADS)

Birjandtalab, Javad; Pouyan, Maziyar Baran; Nourani, Mehrdad

2016-07-01

Epilepsy is a neurological disorder which can, if not controlled, potentially cause unexpected death. It is extremely crucial to have accurate automatic pattern recognition and data mining techniques to detect the onset of seizures and inform care-givers to help the patients. EEG signals are the preferred biosignals for diagnosis of epileptic patients. Most of the existing pattern recognition techniques used in EEG analysis leverage the notion of supervised machine learning algorithms. Since seizure data are heavily under-represented, such techniques are not always practical particularly when the labeled data is not sufficiently available or when disease progression is rapid and the corresponding EEG footprint pattern will not be robust. Furthermore, EEG pattern change is highly individual dependent and requires experienced specialists to annotate the seizure and non-seizure events. In this work, we present an unsupervised technique to discriminate seizures and non-seizures events. We employ power spectral density of EEG signals in different frequency bands that are informative features to accurately cluster seizure and non-seizure events. The experimental results tried so far indicate achieving more than 90% accuracy in clustering seizure and non-seizure events without having any prior knowledge on patient's history.

Epileptic seizure prediction by non-linear methods

DOEpatents

Hively, L.M.; Clapp, N.E.; Day, C.S.; Lawkins, W.F.

1999-01-12

This research discloses methods and apparatus for automatically predicting epileptic seizures monitor and analyze brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis tools; obtaining time serial trends in the nonlinear measures; comparison of the trend to known seizure predictors; and providing notification that a seizure is forthcoming. 76 figs.

Bradycardia and asystole during generalised interictal EEG discharges.

PubMed

Sforza, Emilia; Pichot, Vincent; Gschwind, Markus; Roche, Frédéric; Maeder-Ingvar, Malin

2014-12-01

Few studies have investigated the effects of interictal epileptic discharges on the cardiac autonomic system. This study reports the case of a 37-year-old man with refractory generalised epilepsy, who recently reported an increase in frequency of nocturnal tonic-clonic seizures, not responding to treatment. During the nocturnal video study, in non-rapid eye movements sleep, we recorded 106 generalised sharp- and polyspike-waves lasting for 3 to 7 seconds, associated with bradycardia and asystole, without behavioural changes and without increase in deltoid muscle activity. The asystole had a duration of between 3 and 8 seconds. In one case, a 7 second asystole was associated with a tonic-clonic generalised seizure. A 24-hour electrocardiographic study revealed a bradycardia and a Wenckebach atrioventricular block. Heart rate analysis at the time of the interictal epileptic discharges revealed an abrupt increase in the RR interval, occurring simultaneously with the onset of interictal epileptic discharges and followed by a return to values below baseline value. A cardiac pacemaker was installed with a reduction of asystole length during the interictal epileptic discharges. Our findings indicate, for the first time, the role of interictal generalised discharges in EEG-related asystole and bradycardia. These data support the hypothesis that some patients with epilepsy may be predisposed to disturbances of the autonomic cardiac system.

Reflex seizures in Rett syndrome.

PubMed

Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

2011-12-01

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

Differences in MMPI-2 FBS and RBS scores in brain injury, probable malingering, and conversion disorder groups: a preliminary study.

PubMed

Peck, C P; Schroeder, R W; Heinrichs, R J; Vondran, E J; Brockman, C J; Webster, B K; Baade, L E

2013-01-01

This study examined differences in raw scores on the Symptom Validity Scale and Response Bias Scale (RBS) from the Minnesota Multiphasic Personality Inventory-2 in three criterion groups: (i) valid traumatic brain injured, (ii) invalid traumatic brain injured, and (iii) psychogenic non-epileptic seizure disorders. Results indicate that a >30 raw score cutoff for the Symptom Validity Scale accurately identified 50% of the invalid traumatic brain injured group, while misclassifying none of the valid traumatic brain injured group and 6% of the psychogenic non-epileptic seizure disorder group. Using a >15 RBS raw cutoff score accurately classified 50% of the invalid traumatic brain injured group and misclassified fewer than 10% of the valid traumatic brain injured and psychogenic non-epileptic seizure disorder groups. These cutoff scores used conjunctively did not misclassify any members of the psychogenic non-epileptic seizure disorder or valid traumatic brain injured groups, while accurately classifying 44% of the invalid traumatic brain injured individuals. Findings from this preliminary study suggest that the conjunctive use of the Symptom Validity Scale and the RBS from the Minnesota Multiphasic Personality Inventory-2 may be useful in differentiating probable malingering from individuals with brain injuries and conversion disorders.

Imbalance of community structures in epilepsy

NASA Astrophysics Data System (ADS)

Ortega, G. J.; Herrera Peco, I.; García de Sola, R.; Pastor, J.

2010-09-01

Epilepsy is commonly associated with synchronous activity in the form of spikes and also in developed seizures. Desynchronised activity seems to play an important role also in the seizure process, favouring the initiation of seizures. The aim of the present work is to explore synchronization activity in the inner areas in the temporal lobe of epileptic patients by a novel approach. Two temporal lobe epilepsy (TLE) patients' records have been analyzed through a cluster analysis. Electrical activity in the inner part of the temporal has been recorded by using Foramen Ovale Electrodes (FOE), a semi-invasive technique frequently used in drug resistant epileptic patients. Instead of tracking synchronized activity, we give here special attention to desynchronized activity, mainly those areas which are not included in synchronization clusters. Our results show that electrical activity in the epileptic side behaves in a less cohesive fashion than the contra-lateral side. There exists a clear tendency in the epileptic side to be organized as isolated clusters of electrical activity as compared with the contra-lateral side, which is organized in the form of large clusters of synchronous activity. In particular, we shall give special attention to the cluster desynchronization during the seizures. As we shall show, our results can help in understand several characteristics of the seizures dynamics.

[Magnetoencephalography in the presurgical evaluation of patients with drug-resistant epilepsy].

PubMed

Koptelova, A M; Arkhipova, N A; Golovteev, A L; Chadaev, V A; Grinenko, O A; Kozlova, A B; Novikova, S I; Stepanenko, A Iu; Melikian, A G; Stroganova, T A

2013-01-01

Magnetoencephalography (MEG) in combination with structural MRI (magnetic source imaging, MSI) plays an increasingly important role as one of the tools for presurgical evaluation of medically intractable focal epilepsy. The aim of the study was to compare the MSI and commonly used video EEG monitoring method (vEEG) in their sensitivity to interictal epileptic discharges (IED) in 22 patients with drug resistant epilepsy. Furthermore, the detection and localization results obtained by both methods were verified using the data of electrocorticography (ECoG) and postsurgical outcome in 13 patients who underwent invasive EEG monitoring and surgery. The results showed that MSI was superior to vEEC in terms of sensitivity to IED with difference in sensitivity of 22%. The data also suggested that MSI superiority to vEEG in detecting epileptic discharges might, at least partly, arise from better MEG responsiveness to epileptic events coming from the medial, opercular and basal aspects of cortical lobes. MSI localization estimates were in the same cortical lobe and at the same lobar aspects as the epileptic foci detected by ECoG in all patients. Thus, magnetic source imaging can provide critical localization information that is not available when other noninvasive methods, such as vEEG and MRI, are used.

[Role of video electroencephalogram in diagnosis and localization of epilepsy in children].

PubMed

Yang, Xiao-Yan; Long, Li-Li; Xiao, Bo

2016-10-01

To study the role of video electroencephalogram (VEEG) versus regular electroencephalogram (REEG) in the diagnosis of epilepsy and localization of origin of epileptic discharge in children through a comparative analysis. A retrospective analysis was performed for the clinical data of 223 children with clinical paroxysmal symptoms in the past and suspected epilepsy. VEEG and REEG were compared from the aspects of monitoring of clinical seizures, interictal epileptiform discharge (IED), localization of the origin of IED, and identification of non-epileptic seizures, and the detection rate of IED during awakening and sleep stages was also compared. Compared with REEG, VEEG had significantly higher detection rates of IED and synchronous clinical seizures in children with epileptiform discharge (P<0.01). Of all children, 86 were diagnosed with epilepsy, 78 were diagnosed with epilepsy syndrome, 31 were diagnosed with non-epileptic seizures, and 81 had a definite location of the origin of epileptic discharge according to the VEEG. The detection rate of IED in the sleep stage was higher than that in the awakening stage (46% vs 13.2%; P<0.01), and IED was mainly detected in the NREM I-II stages according to the VEEG. VEEG has a significantly better performance than REEG in the diagnosis and localization of epilepsy in children and has a high value in clinical practice.

CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells

PubMed Central

Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

2012-01-01

Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms involved in its regulation are still unknown. Using human neuroblastoma cells as a model system we found that an increase in CDKL5 expression caused an arrest of the cell cycle in the G0/G1 phases and induced cellular differentiation. Interestingly, CDKL5 expression was inhibited by MYCN, a transcription factor that promotes cell proliferation during brain development and plays a relevant role in neuroblastoma biology. Through a combination of different and complementary molecular and cellular approaches we could show that MYCN acts as a direct repressor of the CDKL5 promoter. Overall our findings unveil a functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation. The fact that CDKL5 is involved in the control of both neuron proliferation and differentiation may help understand the early appearance of neurological symptoms in patients with mutations in CDKL5. PMID:22921766

[The turn of the screw: complex visual hallucinations in the Henry James' novel].

PubMed

Alvaro, L C; Martín Del Burgo, A

2002-03-01

The turn of the screw is one of the most celebrated stories by Henry James. It is also a top writing within the so-called fantastic literature, whose narrative strength comes from the intermittent visions suffered by the main character. The vividness and dramatic content that represent the firstly unidentified human figures, that moreover recur as brief, stereotyped and fragmentary images, are constitutive of complex visual hallucinations. These characteristics, alongside acute premonitory symptoms such as emotional changes (fear, anxiety) or altered thinking (forced, "dejà vu", "jamais vu"), and the final altered awareness or loss of consciousness, allow us to infer an epileptic nature of the ten episodes described. Postictal psychosis, that follows a lucid interval and may last up to the several weeks encompassed by the story, would account for the paranoia featured, in the setting of a temporal lobe epilepsy. The accurate descriptions prompted us to search for autobiographical, scientific or literary influences: The alcoholism and visual hallucinations suffered by his father, the knowledge on hallucinations provided by his brother Williams on his paramount and former The Principles of Psychology, and an early devotion to Poe's writings, an epileptic himself with excellent descriptions of seizures in his writings, might have enabled the author to perform his story with such a hallmark of neurological details.

[Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].

PubMed

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.

Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms.

PubMed

van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

2016-01-01

Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated. Seven weeks after kainic acid-induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human BBB was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for BBB integrity. (Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin-treated rats compared to vehicle-treated rats. In vitro studies showed that rapamycin could attenuate TNFα-induced endothelial barrier breakdown. These data suggest that rapamycin improves BBB function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Alternative therapeutic options for medical management of epilepsy in apes.

PubMed

Gerlach, Trevor; Clyde, Victoria L; Morris, George L; Bell, Barbara; Wallace, Roberta S

2011-06-01

Phenobarbital has been the primary antiepileptic drug used in primates, but the dosage required for seizure control is frequently associated with significant side effects. Newer antiepileptic drugs and adjunctive therapies currently being used in human medicine provide additional options for treatment of nonhuman primates. This report describes different drug regimes used for control of epileptic seizures in apes at the Milwaukee County Zoo (Milwaukee, Wisconsin, U.S.A.), including the addition of acetazolamide to phenobarbital, levetiracetam, carbamazepine, and the use of extended cycle oral contraceptives to assist seizure control in female apes with catamenial epilepsy.

[Anxiety and depression among the epileptics in general population in Benin (Western Africa)].

PubMed

Nubukpo, P; Houinato, D; Preux, P-M; Avodé, G; Clément, J-P

2004-01-01

In order to assess prevalence of depression and anxiety among epileptic patients and to compare it to a control population, a matched case-control survey was performed in 196 persons above 18 Year old (98 epileptics and 98 controls matched according to sex, age 10 and social environment) in Republic of Benin (West Africa), using Goldberg's Depression and Anxiety scale. Two main investigators helped by 5 sociology students were trained on a questionnaire by a psychiatrist skilled with public health matters. People taking part in the survey are epileptic patients who already used health services. Inclusions took place within 17 communes of four departments (Mono, Zou, Ouémé, Atlantique) located in Southern part of Benin. The questionnaire used an Identity sheet and the Goldberg Depression Scale. Results are shown as mean standard deviations, for quantitative values, and percents for qualitative ones. Comparisons of proportions in qualitative variables are carried out using c2 test or Fisher's exact test. Comparisons of means rates between subject's groups are carried out with a Student t test or variance analysis. The correlations between two quantitative variables were assessed by linear correlation coefficient. Significance threshold chosen for the whole set of statistics analysis is 0.05. The majority of interviewed epileptic patients is young (average 32.6 11.5 Years old). A male predominance exists (sex ratio 1.28). 93% of interviewed persons live within their family, are married or cohabit (controls: 98.2%; cases: 87.9%); 57.4% are married (controls: 70%; cases: 44%). The most represented professional categories are craftsmen and shopkeepers (29.2%) as well as farmers (19.5%). Most of recruited patients live in an urban setting (55.4%) and 63.6% of interviewed persons had been living in the area of survey for over 10 Years. The most represented religion within the sample is Christian religion (67.7%), Animists (23.3%) and Muslims (5.8%). 97% of epileptic patients reported they had one fit during the two Years before the survey; roughly one half (48%) had 2 to 5 fits and 41.5% of them had more than 10 fits; only 14% say they have had an EEG. Presence of an Anti Epileptic Drug (77.5%) reduces anxiety and depression. Considering a severity threshold of 5 for anxiety and 2 for depression (8), proportions of epileptic patients displaying a severe anxiety (79.8%) or a severe depression (89.6%) are significantly higher (p<0.0001) than in control subjects (12.3% and 46.9%). Comparison of average scores confirms the difference (p<0.0001) between cases (5.8 2.0 and 2.3 1.9) and controls (4.7 2.4 and 2.0 2.1) regarding anxiety and depression. Neither the sex, nor age, nor life environment (urban/rural), nor frequency of fits hold significant influence over an-xiety and depression. However, results in this survey include higher average rates of anxiety and depression for women (6.3 1.8) than men (5.5 1.8), though such statement is only nearly significant (p=0.06). Results of the survey confirm the other works on this topic about characteristics of depression for epileptic patients, though results here are higher than usual. Anxiety and depression are common troubles found in epileptic patient, both often occurring at the same time. Two distinct theories about this fact are opposed, first explain the connection of anxiety and depression with epilepsy because of the social and cultural burden upon an epileptic patient in those countries, the second theory is about depression and epilepsy sharing some neuroaminergical dysfunctions; these facts were not considered in this survey. When taking into account the thresholds of seriousness on Goldberg's scale, proportion of controls displaying a probably deeper depression is high (46.9%) compared to usual hospital prevalence rates (4 to 25%) found in Western Africa where survey in general population are scarce. It could either be a bias in the selection or the confirmation that family and relatives of an epileptic patient are enduring a great psychic pain too; finally, this high rate o, this high rate of severe depression within controls may suggest a need to adapt thresholds of Goldberg's scale to match African populations. This hypothesis is interesting regarding the results of some Authors who validated this scale in population of aged people; they highlighted the fewer precision of two items (lost of interest, focus difficulties) and also a slight discriminatory weight for other few items. However the psychometric characteristics of Goldberg's scale are accurate (for depression subscale, a sensitivity of 88% and a specificity of 68%; for the whole scale, a sensitivity of 84% and a specificity of 68%). It would be pertinent to carry out a study to validate Goldberg's scale within some African populations. This study also highlights the importance of psychological factors in epilepsy and suggests a specific global care of the disease.

Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

NASA Astrophysics Data System (ADS)

Lopour, Beth A.; Staba, Richard J.; Stern, John M.; Fried, Itzhak; Ringach, Dario L.

2016-04-01

Objective. Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach. Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results. We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance. The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition.

Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

PubMed Central

Lopour, Beth A; Staba, Richard J; Stern, John M; Fried, Itzhak; Ringach, Dario L

2017-01-01

Objective Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition. PMID:26975603

Apparatus and method for epileptic seizure detection using non-linear techniques

DOEpatents

Hively, Lee M.; Clapp, Ned E.; Daw, C. Stuart; Lawkins, William F.

1998-01-01

Methods and apparatus for automatically detecting epileptic seizures by monitoring and analyzing brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis; obtaining time serial trends in the nonlinear measures; determining that one or more trends in the nonlinear measures indicate a seizure, and providing notification of seizure occurrence.

Epilepsy and the law--a view from Thailand.

PubMed

Locharernkul, Chaichon

2007-03-01

Patients with epilepsy often suffer social injustice in many societies. This is a review of current laws dealing with epilepsy and the consequences of this complex disease. The author looked at reported unjust legal and social acts resulting from epileptic seizures and their results. The author found that accusation of criminal acts, accidents while driving, and job loss are relatively common experiences for epileptics. Such events reflect lack of public understanding. There is inadequate legislation to protect epileptics. Most disturbing areas are ictal behavior misinterpreted as crime, driving while experiencing a seizure, and social discrimination. There is no law dealing with epilepsy in Thailand while considerable progress in this field has been made in Western countries. Epilepsy patients are inadequately protected by Thai law. There is an urgent need for education and campaigns for their rights focused on the public, the legal profession, and the health care professionals.

Electroclinical overlap of two types of epileptic encephalopathy occurring in the same children in a certain age period?

PubMed

Caraballo, Roberto Horacio; Soraru, Alejandra; Cersósimo, Ricardo Oscar

2012-08-01

In this study, we describe three patients who each had an electroclinical overlap of two different epileptic encephalopathies (EE), with onset in a certain age period. Patient 1 had electroclinical features compatible with continuous spikes and waves during slow sleep (CSWSS) syndrome that changed into Lennox-Gastaut syndrome (LGS) (symptomatic, cause porencephalic cyst) at the age of 8.5 years. Patient 2 had LGS which evolved into CSWSS at the age of 6 years (symptomatic, cause polymicrogyria). The third patient had cryptogenic CSWSS syndrome at age the age of 7 years which evolved into LGS at the age of 7.5 years. All three patients could be considered to have two EE: CSWSS syndrome and LGS or to have had overlapping features of these epileptic syndromes. Copyright © 2012 Elsevier B.V. All rights reserved.

[Diagnosis of seizures originating in the amygdala and the hippocampus].

PubMed

Padró, L; Rovira, R

1998-02-01

Lesions in the hippocampus of some epileptic patients were first described one hundred and seventy years ago. Since then our knowledge of the relationship between epileptic seizures and temporal lobe lesions has greatly improved. The aim of this paper is to systematize the symptomatology of the hippocampus and amygdala seizures. These seizures may have a great number of different clinical features: special 'loss' or 'impairment of consciousness', epileptic automatisms and autonomic changes. Moreover, at the beginning of seizures some patients have reported experiences having subjective qualities similar to those experienced in everyday life. P Gloor named them 'experiential phenomena' and subdivided them into affective (eg: fear), perceptual (eg: visual hallucinations) and mnemonic (eg: 'déjà vu' illusion). It is very important to know the contribution of the hippocampus and the amygdala to the symptomatology of temporal lobe seizures due to the progress of MRI diagnostic possibilities that are improving the surgical outcome.

Monoamine metabolites, iron induced seizures, and the anticonvulsant effect of tannins.

PubMed

Kabuto, H; Yokoi, I; Mori, A

1992-06-01

Intracortical injections of iron ions have been shown to induce recurrent seizures and epileptic discharges in the EEG. (-)-Epigallocatechin (EGC) and (-)-epigallocatechin-3-O-gallate (EGCG), isolated from green tea leaves, have been reported to prevent or diminish the occurrence of epileptic discharges induced by iron ions, and to inhibit catechol-O-methyltransferase. Iron ions significantly increased DOPAC and HVA levels in the intrastriatal perfusate 140 and 180 minutes, respectively, after injection. EGC and EGCG inhibited the increases induced by iron ions. Furthermore, EGCG decreased the HVA level in the perfusate 200 minutes after injection whether or not iron ions were injected. Iron ions had no effect on the 5-HIAA level, and EGC and EGCG raised it. These results suggest that formation of an epileptic focus induced by iron ions might be accompanied by activation of dopaminergic neurons, and that EGC and EGCG inhibit that hyperactivity.

Alterations in the contents of consciousness in partial epileptic seizures.

PubMed

Johanson, Mirja; Valli, Katja; Revonsuo, Antti; Chaplin, John E; Wedlund, Jan-Eric

2008-08-01

Epilepsy research suffers from a deficiency of systematic studies concerning the phenomenology of the contents of consciousness during seizures, partially because of the lack of suitable research methods. The Phenomenology of Consciousness Inventory (PCI), a standardized, valid, and reliable questionnaire, was used here to study which dimensions of the contents of consciousness are distorted during partial epileptic seizures compared with baseline. Further, the similarity of the altered pattern of subjective experiences across recurring seizures was also explored. Our results indicate that patients with epilepsy report alterations on most dimensions of the contents of consciousness in conjunction with seizures, but individual seizure experiences remain similar from one seizure to another. The PCI was found suitable for the assessment of subjective experiences during epileptic seizures and could be a valuable tool in providing new information about phenomenal consciousness in epilepsy in both the research and clinical settings.

Ethical Dilemmas in Pediatric and Adolescent Psychogenic Non-Epileptic Seizures

PubMed Central

Cole, Cristie M.; Falcone, Tatiana; Caplan, Rochelle; Timmons-Mitchell, Jane; Jares, Kristine; Ford, Paul J.

2014-01-01

To date only a very narrow window of ethical dilemmas in psychogenic non-epileptic seizures (PNES) have been explored. Numerous distinct ethical dilemmas arise in diagnosing and treating pediatric and adolescent patients with PNES. Important ethical values at stake include trust, transparency, confidentiality, professionalism, autonomy of all stakeholders and justice. In order to further elucidate the ethical challenges in caring for this population, an ethical analysis of the special challenges faced in four specific domains is undertaken: (1) conducting and communicating a diagnosis of PNES; (2) advising patients about full transparency and disclosure to community including patients’ peers; (3) responding to requests to continue anti-epileptic drugs; and (4) managing challenges arising from school policy and procedure. An analysis of these ethical issues is essential for the advancement of best care practices that promote the overall well-being of patients and their families. PMID:25022823

Role of oxidative stress in epileptic seizures

PubMed Central

Shin, Eun-Joo; Jeong, Ji Hoon; Chung, Yoon Hee; Kim, Won-Ki; Ko, Kwang-Ho; Bach, Jae-Hyung; Hong, Jau-Shyong; Yoneda, Yukio; Kim, Hyoung-Chun

2013-01-01

Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies aimed at reducing oxidative stress have received considerable attention in epilepsy treatment. However, much evidence suggests that oxidative stress does not always have the same pattern in all seizures models. Thus, this review provides an overview aimed at achieving a better understanding of this issue. We summarize work regarding seizure models (i.e., genetically epilepsy-prone rats, kainic acid, pilocarpine, pentylenetetrazol, and trimethyltin), oxidative stress as an etiologic factor in epileptic seizures (i.e., impairment of antioxidant systems, mitochondrial dysfunction, involvement of redox-active metals, arachidonic acid pathway activation, and aging), and antioxidant strategies for seizure treatment. Combined, this review highlights pharmacological mechanisms associated with oxidative stress in epileptic seizures and the potential for neuroprotection in epilepsy that targets oxidative stress and is supported by effective antioxidant treatment. PMID:21672578

Localizing epileptic seizure onsets with Granger causality

NASA Astrophysics Data System (ADS)

Adhikari, Bhim M.; Epstein, Charles M.; Dhamala, Mukesh

2013-09-01

Accurate localization of the epileptic seizure onset zones (SOZs) is crucial for successful surgery, which usually depends on the information obtained from intracranial electroencephalography (IEEG) recordings. The visual criteria and univariate methods of analyzing IEEG recordings have not always produced clarity on the SOZs for resection and ultimate seizure freedom for patients. Here, to contribute to improving the localization of the SOZs and to understanding the mechanism of seizure propagation over the brain, we applied spectral interdependency methods to IEEG time series recorded from patients during seizures. We found that the high-frequency (>80 Hz) Granger causality (GC) occurs before the onset of any visible ictal activity and causal relationships involve the recording electrodes where clinically identifiable seizures later develop. These results suggest that high-frequency oscillatory network activities precede and underlie epileptic seizures, and that GC spectral measures derived from IEEG can assist in precise delineation of seizure onset times and SOZs.

Role of inhibitory control in modulating focal seizure spread.

PubMed

Liou, Jyun-You; Ma, Hongtao; Wenzel, Michael; Zhao, Mingrui; Baird-Daniel, Eliza; Smith, Elliot H; Daniel, Andy; Emerson, Ronald; Yuste, Rafael; Schwartz, Theodore H; Schevon, Catherine A

2018-05-10

Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts did not propagate beyond a 2-3-mm region, they were associated with hemisphere-wide field potential fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. While bicuculline surface application enhanced contiguous seizure propagation, focal bicuculline microinjection at sites distant to the 4-aminopyridine focus resulted in epileptic network formation with maximal activity at the two foci. Our study suggests that both classical and epileptic network propagation can arise from localized inhibition defects, and that the network appearance can arise in the context of normal brain structure without requirement for pathological connectivity changes between sites.

Topiramate-induced paresthesia is more frequently reported by migraine than epileptic patients.

PubMed

Sedighi, Behnaz; Shafiei, Kaveh; Azizpour, Iman

2016-04-01

Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of topiramate-induced paresthesia in migraine headache to epileptic patients. Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. The odds ratio of developing topiramate-induced paresthesia in migraine compared to epilepsy patients was 3.4. Three factors were independent contributors to developing topiramate-induced paresthesia: female sex (odds ratio 2.1), topiramate dosage (odds ratio 0.3) and duration of therapy. Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as topiramate adverse effects. Female sex, treatment duration and topiramate dosage contribute significantly to subsequent development of paresthesia.

Anti-epileptic drugs in pediatric traumatic brain injury.

PubMed

Tanaka, Tomoko; Litofsky, N Scott

2016-10-01

Pediatric post-traumatic epilepsy incidence varies depending on reporting mechanism and injury severity; anti-epileptic drug (AEDs) use also varies with lack of quality evidence-based data. Adverse AED effects are not negligible; some may negatively affect functional outcome. This review focuses on clarifying available data. This review discusses seizures associated with traumatic brain injury in children, including seizure incidence, relationship to severity of injury, potential detrimental effects of seizures, potential benefits of AED, adverse effects of AED, new developments in preventing epileptogenesis, and suggested recommendations for patient management. English language papers were identified from PubMed using search terms including but not excluding the following: adverse drug effects, anti-epileptic drugs, children, electroencephalogram, epilepsy, epileptogenesis, head injury, levetiracetam, pediatrics, phenytoin, post-traumatic epilepsy, prevention, prophylaxis, seizures, and traumatic brain injury. Expert commentary: Identification of high-risk patients for post-traumatic seizures is a key goal. Levetiracetam may prevent epileptogenesis, as may other developments.

A method for detecting nonlinear determinism in normal and epileptic brain EEG signals.

PubMed

Meghdadi, Amir H; Fazel-Rezai, Reza; Aghakhani, Yahya

2007-01-01

A robust method of detecting determinism for short time series is proposed and applied to both healthy and epileptic EEG signals. The method provides a robust measure of determinism through characterizing the trajectories of the signal components which are obtained through singular value decomposition. Robustness of the method is shown by calculating proposed index of determinism at different levels of white and colored noise added to a simulated chaotic signal. The method is shown to be able to detect determinism at considerably high levels of additive noise. The method is then applied to both intracranial and scalp EEG recordings collected in different data sets for healthy and epileptic brain signals. The results show that for all of the studied EEG data sets there is enough evidence of determinism. The determinism is more significant for intracranial EEG recordings particularly during seizure activity.

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

PubMed Central

Palma, Eleonora; Roseti, Cristina; Maiolino, Francesca; Fucile, Sergio; Martinello, Katiuscia; Mazzuferi, Manuela; Aronica, Eleonora; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Miledi, Ricardo; Simonato, Michele; Eusebi, Fabrizio

2007-01-01

A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease. PMID:18083839

Underlying neurological dysfunction in children with language, speech or learning difficulties and a verbal IQ--performance IQ discrepancy.

PubMed

Meulemans, J; Goeleven, A; Zink, I; Loyez, L; Lagae, L; Debruyne, F

2012-01-01

We investigated the relationship between possible underlying neurological dysfunction and a significant discrepancy between verbal IQ/performance IQ (VIQ-PIQ) in children with language, speech or learning difficulties. In a retrospective study, we analysed data obtained from intelligence testing and neurological evaluation in 49 children with a significant VIQ-PIQ discrepancy (> or = 25 points) who were referred because of language, speech or learning difficulties to the Multidisciplinary University Centre for Logopedics and Audiology (MUCLA) of the University Hospitals of Leuven, Belgium. The group of children broke down into a group of 35 children with PIQ > VIQ and a group of 14 children with VIQ > PIQ. In the first group, neurological data were present for 24 children. The neurological history and clinical neurological examination were normal in all cases. Brain MRI was performed in 15 cases and proved to be normal in all children. Brain activity was assessed with long-term video EEG monitoring in ten children. In two children, the EEG results were abnormal: there was an epileptic focus in one child and a manifest alteration in the EEG typical of Landau-Kleffner syndrome in the other. In the second group of 14 children whose VIQ was higher than the PIQ, neurological data were available for ten children. Neurological history and clinical neurological examination were normal in all cases. Brain MRI was performed in five cases and was normal in all children. EEG monitoring was performed in one child. This revealed benign childhood epilepsy with centrotemporal spikes. In a small number of children (9%) with speech, language and learning difficulties and a discrepancy between VIQ and PIQ, an underlying neurological abnormality is present. We recommend referring children with a significant VIQ-PIQ mismatch to a paediatric neurologist. As an epileptic disorder seems to be the most common underlying neurological pathology in this specific group of children, EEG monitoring should be recommended in these children. Neuro-imaging should only be used in selected patients.

Anticipating epileptic seizures: from mathematics to clinical applications.

PubMed

Le Van Quyen, Michel

2005-02-01

The study of dynamical changes in the neural activity preceding an epileptic seizure allows the characterization of a preictal state several minutes prior to seizure onset. This opens new perspectives for studying the mechanisms of ictogenesis as well as for possible therapeutic interventions that represent a major breakthrough. In this review we present and discuss the results from our group in this domain using nonlinear analysis of brain signals, as well as its limitation and open questions.

Psychomotor epileptic symptoms in six patients with bipolar mood disorders.

PubMed

Lewis, D O; Feldman, M; Greene, M; Martinez-Mustardo, Y

1984-12-01

Of 12 consecutive patients with bipolar mood disorders satisfying DSM-III criteria, six were discovered to have five or more psychomotor epileptic symptoms. All of the six had olfactory hallucinations, metamorphopsias, and multiple déjà vu or mystical experiences. Each of them responded to lithium carbonate and had a first-degree relative with a bipolar disorder. The authors suggest that psychomotor symptoms may be more prevalent in bipolar patients than has hitherto been recognized.

Apparatus and method for epileptic seizure detection using non-linear techniques

DOEpatents

Hively, L.M.; Clapp, N.E.; Daw, C.S.; Lawkins, W.F.

1998-04-28

Methods and apparatus are disclosed for automatically detecting epileptic seizures by monitoring and analyzing brain wave (EEG or MEG) signals. Steps include: acquiring the brain wave data from the patient; digitizing the data; obtaining nonlinear measures of the data via chaotic time series analysis; obtaining time serial trends in the nonlinear measures; determining that one or more trends in the nonlinear measures indicate a seizure, and providing notification of seizure occurrence. 76 figs.

Epileptic syndrome in systemic lupus erythematosus and neuronal autoantibody associations.

PubMed

Kampylafka, E I; Alexopoulos, H; Fouka, P; Moutsopoulos, H M; Dalakas, M C; Tzioufas, A G

2016-10-01

We investigated systemic lupus erythematosus (SLE) patients with epilepsy, a major and organic neurological symptom. Our aim was to test patients for the autoimmune epilepsy-associated antibodies anti-GAD, anti-NMDAR, anti-AMPAR1/2, anti-GABABR and anti-VGKC. We tested sera from ten SLE patients with current or previous episodes of epileptic seizures. In addition, sera were tested for staining on primary hippocampal neurons. The patients' clinical and neuroimaging profile, disease activity and accumulated damage scores and therapeutic regimens administered were recorded, and correlations were evaluated. Patients were negative for all anti-neuronal autoantibodies tested, and showed no staining on primary hippocampal cells, which suggests the absence of autoantibodies against neuronal cell surface antigens. Epileptic seizures were all tonic-clonic, and all patients had high disease activity (mean SLE Damage Acticity Index score 19.3 ± 7.3). Six patients had minor or no brain magnetic resonance imaging findings, and three had major findings. 9/10 patients received immunosuppression for 5 ± 4 months, while anti-convulsive treatment was administered to all patients (4.2 ± 3 years). Our results suggest that the majority of SLE-related epileptic seizures cannot be attributed to the action of a single antibody against neuronal antigens. Studies with larger neuropsychiatric SLE populations and stricter inclusion criteria are necessary to verify these findings. © The Author(s) 2016.

Hidden pattern discovery on epileptic EEG with 1-D local binary patterns and epileptic seizures detection by grey relational analysis.

PubMed

Kaya, Yılmaz

2015-09-01

This paper proposes a novel approach to detect epilepsy seizures by using Electroencephalography (EEG), which is one of the most common methods for the diagnosis of epilepsy, based on 1-Dimension Local Binary Pattern (1D-LBP) and grey relational analysis (GRA) methods. The main aim of this paper is to evaluate and validate a novel approach, which is a computer-based quantitative EEG analyzing method and based on grey systems, aimed to help decision-maker. In this study, 1D-LBP, which utilizes all data points, was employed for extracting features in raw EEG signals, Fisher score (FS) was employed to select the representative features, which can also be determined as hidden patterns. Additionally, GRA is performed to classify EEG signals through these Fisher scored features. The experimental results of the proposed approach, which was employed in a public dataset for validation, showed that it has a high accuracy in identifying epileptic EEG signals. For various combinations of epileptic EEG, such as A-E, B-E, C-E, D-E, and A-D clusters, 100, 96, 100, 99.00 and 100% were achieved, respectively. Also, this work presents an attempt to develop a new general-purpose hidden pattern determination scheme, which can be utilized for different categories of time-varying signals.

Should epidural drain be recommended after supratentorial craniotomy for epileptic patients?

PubMed

Guangming, Zhang; Huancong, Zuo; Wenjing, Zhou; Guoqiang, Chen; Xiaosong, Wang

2009-08-01

ED was once and is still commonly applied to prevent mainly EH and subgaleal CSF collection. We designed this study to observe if ED could decrease the incidence and volume of EH and subgaleal CSF collection after supratentorial craniotomy in epileptic patients. Three hundred forty-two epileptic patients were divided into 2 groups according to their first craniotomy date (group 1 in odd date and group 2 in even date). Patients in group 1 had ED and those in group 2 had no ED. The patient numbers and volumes of EH and subgaleal CSF collections in both groups were recorded and statistically analyzed. There were 22 EHs in group 1 and 20 EHs in group 2. There were 11 and 10 subgaleal CSF collections in groups 1 and 2, respectively. The average volume of EH was 13.5 +/- 8.12 and 14.65 +/- 7.72 mL in groups 1 and 2, respectively. The average volume of subgaleal CSF collection was 42.76 +/- 12.09 and 43.75 +/- 11.44 mL in groups 1 and 2, respectively. There were no statistical differences in the incidence and average volume of EH and subgaleal CSF collection between the 2 groups. ED cannot decrease the incidence and volume of EH and subgaleal CSF collection. ED should not be recommended after supratentorial epileptic craniotomy.

Information-seeking behaviour for epilepsy: an infodemiological study of searches for Wikipedia articles.

PubMed

Brigo, Francesco; Otte, Willem M; Igwe, Stanley C; Ausserer, Harald; Nardone, Raffaele; Tezzon, Frediano; Trinka, Eugen

2015-12-01

Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopaedia used by patients and physicians to search for health-related information. Our aim was to evaluate information-seeking behaviour of English-speaking internet users searching Wikipedia for articles related to epilepsy and epileptic seizures. Using Wiki Trends, which provides quantitative information on daily viewing of articles, data on global search queries for Wikipedia articles related to epilepsy and seizures were analysed. The daily Wikipedia article views on syncope, psychogenic non-epileptic seizures, migraine, and multiple sclerosis served as comparative data. The period of analysis covered was from January 2008 to December 2014. Overall, the Wikipedia article "epilepsy and driving" was found to be more frequently visited than the articles "epilepsy and employment" or "epilepsy in children". Since January 2008, the Wikipedia article "multiple sclerosis" was more often visited compared to the articles "epilepsy", "syncope", "psychogenic non-epileptic seizures" or "migraine"; the article "epilepsy" ranked 3,779 and was less frequently visited than "multiple sclerosis", ranked at 571, in traffic on Wikipedia. The highest peak in search volume for the article "epilepsy" coincided with the news of a celebrity having seizures. Fears and worries about epileptic seizures, their impact on driving and employment, and news about celebrities with epilepsy might be major determinants in searching Wikipedia for information.

Variable expressivity of a likely pathogenic variant in KCNQ2 in a three-generation pedigree presenting with intellectual disability with childhood onset seizures.

PubMed

Hewson, Stacy; Puka, Klajdi; Mercimek-Mahmutoglu, Saadet

2017-08-01

KCNQ2 has been reported as a frequent cause of autosomal dominant benign familial neonatal seizures. De novo likely pathogenic variants in KCNQ2 have been described in neonatal or early infantile onset epileptic encephalopathy patients. Here, we report a three-generation family with six affected patients with a novel likely pathogenic variant (c.628C>T; p.Arg210Cys) in KCNQ2. Four family members, three adults and a child, presented with a childhood seizure onset with variability in the severity of seizures and response to treatment, intellectual disability (ID) as well as behavioral problems. The two youngest affected patients had a variable degree of global developmental delay with no seizures at their current age. This three-generation family with six affected members expands the phenotypic spectrum of KCNQ2 associated encephalopathy to KCNQ2 associated ID and or childhood onset epileptic encephalopathy. We think that KCNQ2 associated epileptic encephalopathy should be included in the differential diagnosis of childhood onset epilepsy and early onset global developmental delay, cognitive dysfunction, or ID. Furthermore, whole exome sequencing in families with ID and history of autosomal dominant inheritance pattern with or without seizures, may further broaden the phenotypic spectrum of KCNQ2 associated epileptic encephalopathy or encephalopathy. © 2017 Wiley Periodicals, Inc.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

PubMed

Dinkelacker, Vera; Xin, Xu; Baulac, Michel; Samson, Séverine; Dupont, Sophie

2016-09-01

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity. Copyright © 2016. Published by Elsevier Inc.

Exploring the Epileptic Brain Network Using Time-Variant Effective Connectivity and Graph Theory.

PubMed

Storti, Silvia Francesca; Galazzo, Ilaria Boscolo; Khan, Sehresh; Manganotti, Paolo; Menegaz, Gloria

2017-09-01

The application of time-varying measures of causality between source time series can be very informative to elucidate the direction of communication among the regions of an epileptic brain. The aim of the study was to identify the dynamic patterns of epileptic networks in focal epilepsy by applying multivariate adaptive directed transfer function (ADTF) analysis and graph theory to high-density electroencephalographic recordings. The cortical network was modeled after source reconstruction and topology modulations were detected during interictal spikes. First a distributed linear inverse solution, constrained to the individual grey matter, was applied to the averaged spikes and the mean source activity over 112 regions, as identified by the Harvard-Oxford Atlas, was calculated. Then, the ADTF, a dynamic measure of causality, was used to quantify the connectivity strength between pairs of regions acting as nodes in the graph, and the measure of node centrality was derived. The proposed analysis was effective in detecting the focal regions as well as in characterizing the dynamics of the spike propagation, providing evidence of the fact that the node centrality is a reliable feature for the identification of the epileptogenic zones. Validation was performed by multimodal analysis as well as from surgical outcomes. In conclusion, the time-variant connectivity analysis applied to the epileptic patients can distinguish the generator of the abnormal activity from the propagation spread and identify the connectivity pattern over time.

Epileptic negative drop attacks in atypical benign partial epilepsy: a neurophysiological study.

PubMed

Hirano, Yoshiko; Oguni, Hirokazu; Osawa, Makiko

2009-03-01

We conducted a computer-assisted polygraphic analysis of drop attacks in a child with atypical benign partial epilepsy (ABPE) to investigate neurophysiological characteristics. The patient was a six-year two-month-old girl, who had started to have focal motor seizures, later combined with daily epileptic negative myoclonus (ENM) and drop attacks, causing multiple injuries. We studied episodes of ENM and drop attacks using video-polygraphic and computer-assisted back-averaging analysis. A total of 12 ENM episodes, seven involving the left arm (ENMlt) and five involving both arms (ENMbil), and five drop attacks were captured for analysis. All episodes were time-locked to spike-and-wave complexes (SWC) arising from both centro-temporo-parietal (CTP) areas. The latency between the onset of SWC and ENMlt, ENMbil, and drop attacks reached 68 ms, 42 ms, and 8 ms, respectively. The height of the spike as well as the slow-wave component of SWC for drop attacks were significantly larger than that for both ENMlt and ENMbil (p < 0.05). Drop attacks were considered to be epileptic negative myoclonus involving not only upper proximal but also axial muscles, causing the body to fall. Thus, drop attacks in ABPE are considered to be epileptic negative drop attacks arising from bilateral CTP foci and differ from drop attacks of a generalized origin seen in Lennox-Gastaut syndrome and myoclonic-astatic epilepsy.

Population pharmacokinetic analysis for 10-monohydroxy derivative of oxcarbazepine in pediatric epileptic patients shows no difference between Japanese and other ethnicities.

PubMed

Sugiyama, Ikuo; Bouillon, Thomas; Yamaguchi, Masayuki; Suzuki, Hikoe; Hirota, Takashi; Fink, Martin

2015-04-01

Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

ALA-induced PpIX fluorescence in epileptogenic tissue

NASA Astrophysics Data System (ADS)

Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

Millivolt-scale DC shifts in the human scalp EEG: evidence for a nonneuronal generator.

PubMed

Voipio, Juha; Tallgren, Pekka; Heinonen, Erkki; Vanhatalo, Sampsa; Kaila, Kai

2003-04-01

Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO(2) levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo- or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 microV/s at the vertex (Cz) and an extremely steep dependence (up to 100 microV/mmHg) on the end-tidal Pco(2). This shift had a maximum of up to -2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO(2)-95% O(2), which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO(2) in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco(2)-dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco(2), are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.

Crowdsourcing reproducible seizure forecasting in human and canine epilepsy.

PubMed

Brinkmann, Benjamin H; Wagenaar, Joost; Abbot, Drew; Adkins, Phillip; Bosshard, Simone C; Chen, Min; Tieng, Quang M; He, Jialune; Muñoz-Almaraz, F J; Botella-Rocamora, Paloma; Pardo, Juan; Zamora-Martinez, Francisco; Hills, Michael; Wu, Wei; Korshunova, Iryna; Cukierski, Will; Vite, Charles; Patterson, Edward E; Litt, Brian; Worrell, Gregory A

2016-06-01

SEE MORMANN AND ANDRZEJAK DOI101093/BRAIN/AWW091 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : Accurate forecasting of epileptic seizures has the potential to transform clinical epilepsy care. However, progress toward reliable seizure forecasting has been hampered by lack of open access to long duration recordings with an adequate number of seizures for investigators to rigorously compare algorithms and results. A seizure forecasting competition was conducted on kaggle.com using open access chronic ambulatory intracranial electroencephalography from five canines with naturally occurring epilepsy and two humans undergoing prolonged wide bandwidth intracranial electroencephalographic monitoring. Data were provided to participants as 10-min interictal and preictal clips, with approximately half of the 60 GB data bundle labelled (interictal/preictal) for algorithm training and half unlabelled for evaluation. The contestants developed custom algorithms and uploaded their classifications (interictal/preictal) for the unknown testing data, and a randomly selected 40% of data segments were scored and results broadcasted on a public leader board. The contest ran from August to November 2014, and 654 participants submitted 17 856 classifications of the unlabelled test data. The top performing entry scored 0.84 area under the classification curve. Following the contest, additional held-out unlabelled data clips were provided to the top 10 participants and they submitted classifications for the new unseen data. The resulting area under the classification curves were well above chance forecasting, but did show a mean 6.54 ± 2.45% (min, max: 0.30, 20.2) decline in performance. The kaggle.com model using open access data and algorithms generated reproducible research that advanced seizure forecasting. The overall performance from multiple contestants on unseen data was better than a random predictor, and demonstrates the feasibility of seizure forecasting in canine and human epilepsy.media-1vid110.1093/brain/aww045_video_abstractaww045_video_abstract. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Epilepsy and education in developing countries: a survey of school teachers' knowledge about epilepsy and their attitude towards students with epilepsy in Northwestern Nigeria.

PubMed

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.

Quantitative analysis of surface electromyography during epileptic and nonepileptic convulsive seizures.

PubMed

Beniczky, Sándor; Conradsen, Isa; Moldovan, Mihai; Jennum, Poul; Fabricius, Martin; Benedek, Krisztina; Andersen, Noémi; Hjalgrim, Helle; Wolf, Peter

2014-07-01

To investigate the characteristics of sustained muscle activation during convulsive epileptic and psychogenic nonepileptic seizures (PNES), as compared to voluntary muscle activation. The main goal was to find surface electromyography (EMG) features that can distinguish between convulsive epileptic seizures and convulsive PNES. In this case-control study, surface EMG was recorded from the deltoid muscles during long-term video-electroencephalography (EEG) monitoring in 25 patients and in 21 healthy controls. A total of 46 clinical episodes were recorded: 28 generalized tonic-clonic seizures (GTCS) from 14 patients with epilepsy, and 18 convulsive PNES from 12 patients (one patient had both GTCS and PNES). The healthy controls were simulating GTCS. To quantitatively characterize the signals we calculated the following parameters: root mean square (RMS) of the amplitude, median frequency (MF), coherence, and duration of the seizures, of the clonic EMG discharges, and of the silent periods between the cloni. Based on wavelet analysis, we distinguished between a low-frequency component (LF 2-8 Hz) and a high-frequency component (HF 64-256 Hz). Duration of the seizure, and separation between the tonic and the clonic phases distinguished at group-level but not at individual level between convulsive PNES and GTCS. RMS, temporal dynamics of the HF/LF ratio, and the evolution of the silent periods differentiated between epileptic and nonepileptic convulsive seizures at the individual level. A combination between HF/LF ratio and RMS separated all PNES from the GTCS. A blinded review of the EMG features distinguished correctly between GTCS and convulsive PNES in all cases. The HF/LF ratio and the RMS of the PNES were smaller compared to the simulated seizures. In addition to providing insight into the mechanism of muscle activation during convulsive PNES, these results have diagnostic significance, at the individual level. Surface EMG features can accurately distinguish convulsive epileptic from nonepileptic psychogenic seizures, even in PNES cases without rhythmic clonic movements. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Epilepsy and Education in developing countries: a survey of school teachers’ knowledge about epilepsy and their attitude towards students with epilepsy in Northwestern Nigeria

PubMed Central

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

Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy.

PubMed

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 development of a chronic epileptic state that is characterized by (i) a latent period before the onset of chronic motor seizures, and (ii) a high but variable seizure frequency that initially increases with time after the first chronic seizure. This modification of the kainate-treatment protocol is efficient and relatively simple, and the properties of the chronic epileptic state appear similar to severe human temporal lobe epilepsy. Furthermore, the observation that seizure frequency initially increased as a function of time after kainate treatment supports the hypothesis that temporal lobe epilepsy can be a progressive syndrome.

Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures.

PubMed

Yang, Dong-Ping; Robinson, P A

2017-04-01

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures

NASA Astrophysics Data System (ADS)

Yang, Dong-Ping; Robinson, P. A.

2017-04-01

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

Biotelemetry system for Epilepsy Seizure Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, LaCurtise; Bohnert, George W.

2009-07-02

The Biotelemetry System for Epilepsy Seizure Control Project developed and tested an automated telemetry system for use in an epileptic seizure prevention device that precisely controls localized brain temperature. This project was a result of a Department of Energy (DOE) Global Initiatives for Proliferation Prevention (GIPP) grant to the Kansas City Plant (KCP), Argonne National Laboratory (ANL), and Pacific Northwest National Laboratory (PNNL) to partner with Flint Hills Scientific, LLC, Lawrence, KS and Biophysical Laboratory Ltd (BIOFIL), Sarov, Russia to develop a method to help control epileptic seizures.

[Non-epileptic paroxysmal sleep disorders].

PubMed

Malagón-Valdez, Jorge

2013-09-06

Non-epileptic paroxysmal disorders during sleep are a great challenge for the clinician. It is important to know the various clinical manifestations for appropriate differential diagnosis, since alterations in sleep, mostly motor, are part of these disorders. Our paper describes the normal sleep stages and electroencephalographic characteristics and polysomnography basic data. The confusions especially with nocturnal frontal lobe epilepsy are frequent and cause unnecessary drugs administered, the emotional burden of the parents or caretakers, which is the diagnosis of epilepsy. We discuss the possible causes of diagnostic errors.

Extreme startle and photomyoclonic response in severe hypocalcaemia.

PubMed

Moccia, Marcello; Erro, Roberto; Nicolella, Elvira; Striano, Pasquale; Striano, Salvatore

2014-03-01

We report the case of 62-year-old woman referred to our department because of a clinical suspicion of tonic-clonic seizures. Clinical examination revealed an exaggerated startle reflex, EEG showed a photomyoclonic response, and blood tests indicated severe hypocalcaemia. Additional clinical data, treatment strategies, and long-term follow-up visits were reported. The present report discusses the difficulties in distinguishing between epileptic and non-epileptic startles, and shows, for the first time, exaggerated startle reflex and extreme photomyoclonic response due to severe hypocalcaemia.

Excitatory amino acids in epilepsy and potential novel therapies.

PubMed

Meldrum, B S

1992-07-01

Evidence that an abnormality of excitatory neurotransmission may contribute to the epileptic phenomena in various animal and human syndromes is reviewed. Altered glutamate transport or metabolism may be a contributory factor in some genetic syndromes and enhanced responsiveness to activation of NMDA receptors may be significant in various acquired forms of epilepsy. Decreasing glutamatergic neurotransmission provides a rational therapeutic approach to epilepsy. Potent anticonvulsant effects are seen with the acute administration of NMDA antagonists in a wide range of animal models. Some competitive antagonists acting at the NMDA/glutamate site show prolonged anticonvulsant activity following oral administration at doses free of motor side effects and appear suitable for clinical trial.

Adjunctive antiepileptic drugs in adult epilepsy: how the first add-on could be the last.

PubMed

Cretin, Benjamin; Hirsch, Edouard

2010-05-01

In adult epilepsies, incomplete seizure control under monotherapy affects approximately 20-25% of patients with idiopathic generalized epilepsies (IGE) and approximately 20-40% of patients with epilepsies with focal seizures (FE). The choice of an adjunctive therapy is therefore a common event. Efficacy studies of add-on anti-epileptic drugs for adult epilepsies--approved since the early 1990s until 2008--were reviewed. An exception was made for valproate. Efficacy studies give important clues for add-on drug choice but--beyond this--we encourage physicians to consider other parameters, especially co-morbidity(ies) and special situation(s). According to clinical and pharmacological data, an original, practical approach is proposed, by which decisions are based on three main criteria, which aim to optimize patients' seizure control and quality of life. The need for drugs that act not only on 'ictogenesis' but also on 'epileptogenesis' is also discussed briefly. Given the increasing disposal of anti-epileptic drugs, the choice of an add-on therapy appears to be partly based on subjective criteria (physician opinions and preferences). In fact, the selection criteria can be clarified as: treatment decisions rely not only on seizure type, efficacy and tolerability profiles but also on patient-related factors.

Recurrence of conversion disorder symptoms in a successfully treated 16-year-old female.

PubMed

Shapiro, Michael; Mehta, Anuja; Avila, Jorge; Nguyen, Mathew

2015-01-01

We present a case of a 16-year-old Caucasian female with a history of major depressive disorder and post-traumatic stress disorder who was admitted to an inpatient adolescent psychiatric unit with symptoms of conversion disorder, including non-epileptic seizures, an inability to speak or walk, and not eating on her own. She has a history of multiple previous medical and psychiatric hospitalizations without any significant resolution of symptoms, and extensive medical workups have all been negative. Treatment ultimately involved reassuring the patient and family that there was no underlying medical condition and emphasizing the conversion disorder diagnosis. The patient participated daily in physical therapy to improve mobility, deconditioning, and functioning. Hospital staff was instructed on the nature of the non-epileptic seizures, which continued to occur during the hospitalization. After one month, the patient was discharged home fully functional: walking, speaking, and eating on her own. One week after discharge, the patient presented with the same symptoms and was readmitted to the psychiatric facility. She subsequently never regained her previous level of functioning, and she was ultimately transferred to a residential treatment facility. We will discuss factors that led to the initial improvement and the factors that led to recurrence and persistence of symptoms. © The Author(s) 2015.

Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presenting as acute meningoencephalitis: a case report.

PubMed

Hsu, Yu-Chuan; Yang, Fu-Chi; Perng, Cherng-Lih; Tso, An-Chen; Wong, Lee-Jun C; Hsu, Chang-Hung

2012-09-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Epileptic seizures are common features of both MELAS and meningoencephalitis and are typically treated with anticonvulsants. To provide the reader with a better understanding of MELAS and the adverse effects of valproic acid. A 47-year-old man with a history of diabetes, hearing loss, sinusitis, and otitis media was brought to our emergency department due to acute onset of fever, headache, generalized seizure, and agitation. Because acute meningoencephalitis was suspected, the patient was treated with antibiotics on an empirical basis. The seizure activity was aggravated by valproic acid and abated after its discontinuation. MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. Detailed history-taking and systematic review help emergency physicians differentiate MELAS from meningoencephalitis in patients with the common presentation of epileptic seizures. Use of valproic acid to treat epilepsy in patients suspected of having mitochondrial disease should be avoided. Underlying mitochondrial disease should be suspected if seizure activity worsens with valproic acid therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Spatial and Temporal EEG-fMRI Changes During Preictal and Postictal Phases in a Patient With Posttraumatic Epilepsy.

PubMed

Storti, Silvia F; Del Felice, Alessandra; Formaggio, Emanuela; Boscolo Galazzo, Ilaria; Bongiovanni, Luigi G; Cerini, Roberto; Fiaschi, Antonio; Manganotti, Paolo

2015-07-01

The combined use of electroencephalography (EEG) and functional magnetic resonance imaging (EEG-fMRI) in epilepsy allows the noninvasive hemodynamic characterization of epileptic discharge-related neuronal activations. The aim of this study was to investigate pathophysiologic mechanisms underlying epileptic activity by exploring the spatial and temporal distribution of fMRI signal modifications during seizure in a single patient with posttraumatic epilepsy. EEG and fMRI data were acquired during two scanning sessions: a spontaneous critical episode was observed during the first, and interictal events were recorded during the second. The EEG-fMRI data were analyzed using the general linear model (GLM). Blood oxygenation level-dependent (BOLD) localization derived from the preictal and artifact-free postictal phase was concordant with the BOLD localization of the interictal epileptiform discharges identified in the second session, pointing to a left perilesional mesiofrontal area. Of note, BOLD signal modifications were already visible several seconds before seizure onset. In brief, BOLD activations from the preictal, postictal, and interictal epileptiform discharge analysis appear to be concordant with the clinically driven localization hypothesis, whereas a widespread network of activations is detected during the ictal phase in a partial seizure. © EEG and Clinical Neuroscience Society (ECNS) 2014.

[The mind and epilepsy: opinions and viewpoints over the course of time].

PubMed

Vaney, C

1989-07-18

Among the very few diseases that can be traced back to ancient times none has stimulated human phantasy as much as epilepsy, and the many names given to epilepsy reflects the different trends of thinking on the topic over the past two and a half thousand years. The ancient Greek believed epilepsy to be a sacred disease with the body being invaded by a God. The view that demons and evil spirits rather than Gods were responsible for the disease prevailed throughout the middle ages, influenced by Christian thinking. This led people with epilepsy to be treated, as the mentally ill, with contempt and pity. Up to the latter half of the 19th century epilepsy remained an integral part of psychiatry. The concept of the epileptic personality, stating that the behaviour and consequently the seizures themselves came from a constitutional hereditary psychopathic make-up, was deeply entrenched. The process of distinguishing epilepsy from insanity began with the development of neurology as a new and independent discipline, helped by the discovery of electroencephalography EEG and potent antiepileptic drugs. It became more widely accepted that most epileptic patients have normal mental states. It was argued that the psychiatric consequences of having epilepsy depended on the existence of pathological brain lesions, side-effects of inadequate drugs and the psychological stress of living with a chronic and debilitating disease.

CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells.

PubMed

Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

2012-01-01

Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms involved in its regulation are still unknown. Using human neuroblastoma cells as a model system we found that an increase in CDKL5 expression caused an arrest of the cell cycle in the G(0)/G(1) phases and induced cellular differentiation. Interestingly, CDKL5 expression was inhibited by MYCN, a transcription factor that promotes cell proliferation during brain development and plays a relevant role in neuroblastoma biology. Through a combination of different and complementary molecular and cellular approaches we could show that MYCN acts as a direct repressor of the CDKL5 promoter. Overall our findings unveil a functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation. The fact that CDKL5 is involved in the control of both neuron proliferation and differentiation may help understand the early appearance of neurological symptoms in patients with mutations in CDKL5. Copyright © 2012 Elsevier B.V. All rights reserved.

Music and its association with epileptic disorders.

PubMed

Maguire, Melissa

2015-01-01

The association between music and epileptic seizures is complex and intriguing. Musical processing within the human brain recruits a network which involves many cortical areas that could activate as part of a temporal lobe seizure or become hyperexcitable on musical exposure as in the case of musicogenic epilepsy. The dichotomous effect of music on seizures may be explained by modification of dopaminergic circuitry or counteractive cognitive and sensory input in ictogenesis. Research has explored the utility of music as a therapy in epilepsy and while limited studies show some evidence of an effect on seizure activity; further work is required to ascertain its clinical potential. Sodium channel-blocking antiepileptic drugs, e.g., carbamazepine and oxcarbazepine, appear to effect pitch perception particularly in native-born Japanese, a rare but important adverse effect, particularly if a professional musician. Temporal lobe surgery for right lateralizing epilepsy has the capacity to effect all facets of musical processing, although risk and correlation to resection area need further research. There is a need for the development of investigative tools of musical processing that could be utilized along the surgical pathway. Similarly, work is also required in devising a musical paradigm as part of electroencephalography to improve surveillance of musicogenic seizures. These clinical applications could aid the management of epilepsy and preservation of musical ability. © 2015 Elsevier B.V. All rights reserved.

SVM-Based System for Prediction of Epileptic Seizures from iEEG Signal

PubMed Central

Cherkassky, Vladimir; Lee, Jieun; Veber, Brandon; Patterson, Edward E.; Brinkmann, Benjamin H.; Worrell, Gregory A.

2017-01-01

Objective This paper describes a data-analytic modeling approach for prediction of epileptic seizures from intracranial electroencephalogram (iEEG) recording of brain activity. Even though it is widely accepted that statistical characteristics of iEEG signal change prior to seizures, robust seizure prediction remains a challenging problem due to subject-specific nature of data-analytic modeling. Methods Our work emphasizes understanding of clinical considerations important for iEEG-based seizure prediction, and proper translation of these clinical considerations into data-analytic modeling assumptions. Several design choices during pre-processing and post-processing are considered and investigated for their effect on seizure prediction accuracy. Results Our empirical results show that the proposed SVM-based seizure prediction system can achieve robust prediction of preictal and interictal iEEG segments from dogs with epilepsy. The sensitivity is about 90–100%, and the false-positive rate is about 0–0.3 times per day. The results also suggest good prediction is subject-specific (dog or human), in agreement with earlier studies. Conclusion Good prediction performance is possible only if the training data contain sufficiently many seizure episodes, i.e., at least 5–7 seizures. Significance The proposed system uses subject-specific modeling and unbalanced training data. This system also utilizes three different time scales during training and testing stages. PMID:27362758

Déjà vu phenomenon-related EEG pattern. Case report.

PubMed

Vlasov, P N; Chervyakov, A V; Gnezditskii, V V

2013-01-01

Déjà vu (DV, from French déjà vu - "already seen") is an aberration of psychic activity associated with transitory erroneous perception of novel circumstances, objects, or people as already known. This study aimed to record the EEG pattern of déjà vu. The subjects participated in a survey concerning déjà vu characteristics and underwent ambulatory EEG monitoring (12-16 h). In patients with epilepsy, DV episodes began with polyspike activity in the right temporal lobe region and, in some cases, ended with slow-wave theta-delta activity over the right hemisphere. There were no epileptic discharges in healthy respondents during DV. Two types of déjà vu are suggested to exist: "pathological-epileptic" déjà vu, characteristic of patients with epilepsy and equivalent to an epileptic seizure, and "nonpathological-nonepileptic" déjà vu, which is characteristic of healthy people and psychological phenomenon.

Diagnostic outcomes of inpatient video electroencephalography: nonepileptic events in South Carolina.

PubMed

Koontz, Elizabeth H; Hanson, Jarom; Pritchard, Paul B

2013-09-01

The Epilepsy Monitoring Unit (EMU) was established at the Medical University Hospital to assist in the diagnosis of epilepsy and the evaluation of other paroxysmal neurological symptoms, including non-epileptic events (NEEs), which are often confused with epileptic seizures. Correct diagnosis can prevent inappropriate treatment with antiepileptic drugs, avoid some of the restrictions imposed by epileptic seizures, and facilitate appropriate treatment for NEEs. A retrospective review of patients admitted to the EMU over a two year period showed the percentage of patients diagnosed with NEEs (39%) is greater than those diagnosed with epilepsy alone (36%). This incidence of NEE is higher than in other academic medical centers. The explanations for this disparity are not fully defined, but warrant further study as to patient demographics, risk factors, and referral patterns in South Carolina. The average time from when patients began having events to accurate diagnosis of NEEs was 4.5 years, and 21 patients had NEEs for at least 10 years prior to diagnosis.

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

PubMed

Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p < 0.05). Corresponding relative ln (concentration-dose ratios) values for SCN1A IVS5-91 variants differed by the genotypic order GG > GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Investigation of phase synchronization of interictal EEG in right temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Yu, Haitao; Cai, Lihui; Wu, Xinyu; Song, Zhenxi; Wang, Jiang; Xia, Zijie; Liu, Jing; Cao, Yibin

2018-02-01

Epilepsy is commonly associated with abnormally synchronous activity of neurons located in epileptogenic zones. In this study, we investigated the synchronization characteristic of right temporal lobe epilepsy (RTLE). Multichannel electroencephalography (EEG) data were recorded from the RTLE patients during interictal period and normal controls. Power spectral density was first used to analyze the EEG power for two groups of subjects. It was found that the power of epileptics is increased in the whole brain compared with that of the control. We calculated phase lag index (PLI) to measure the phase synchronization between each pair of EEG signals. A higher degree of synchronization was observed in the epileptics especially between distant channels. In particular, the regional synchronization degree was negatively correlated with power spectral density and the correlation was weaker for epileptics. Moreover, the synchronization degree decayed with the increase of relative distance of channels for both the epilepsy and control, but the dependence was weakened in the former. The obtained results may provide new insights into the generation mechanism of epilepsy.

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.

Heterogeneous integration of adult-generated granule cells into the epileptic brain

PubMed Central

Murphy, Brian L.; Pun, Raymund Y.K.; Yin, Hulian; Faulkner, Christian R.; Loepke, Andreas W.; Danzer, Steve C.

2011-01-01

The functional impact of adult-generated granule cells in the epileptic brain is unclear, with data supporting both protective and maladaptive roles. These conflicting findings could be explained if new granule cells integrate heterogeneously, with some cells taking neutral or adaptive roles, while others contribute to recurrent circuitry supporting seizures. Here, we tested this hypothesis by completing detailed morphological characterizations of age- and experience-defined cohorts of adult-generated granule cells from transgenic mice. The majority of newborn cells exposed to an epileptogenic insult exhibited reductions in dendritic spine number, suggesting reduced excitatory input to these cells. A significant subset, however, exhibited higher spine numbers. These latter cells tended to have enlarged cell bodies, long basal dendrites or both. Moreover, cells with basal dendrites received significantly more recurrent mossy fiber input through their apical dendrites, indicating that these cells are robustly integrated into the pathological circuitry of the epileptic brain. These data imply that newborn cells play complex – and potentially conflicting – roles in epilepsy. PMID:21209195

Relations between epileptic seizures and headaches.

PubMed

Gameleira, Fernando Tenório; Ataíde, Luiz; Raposo, Maria Cristina Falcão

2013-10-01

To describe headaches in patients with epilepsy and try to identify relations between epileptic seizures and headaches. Cross-sectional study, with 304 patients from the epilepsy out-patient section of University Hospital of Federal University of Alagoas (Brazil) between February 2007 and February 2008. The presence of headaches and their relationships with the epileptic seizures were analyzed. Frequent seizures were associated with a greater tendency of occurrence of headaches (odds ratio=1.6 times, p=0.077). Headaches occurred in 66.1% of the cases. The highest occurrence was of migraine (32.9% of the patients), followed by tension-type headaches (9.2%). Two syndromes with a continuum epilepsy-migraine in the same seizure are worth mentioning: migralepsy in 6.6% and epilepgraine in 10.2% of the patients with epilepsy. A high prevalence of headaches in patients with epilepsy was observed, with emphasis on hybrid crises of epilepsy and migraine. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Mechanisms for Selective Single-Cell Reactivation during Offline Sharp-Wave Ripples and Their Distortion by Fast Ripples.

PubMed

Valero, Manuel; Averkin, Robert G; Fernandez-Lamo, Ivan; Aguilar, Juan; Lopez-Pigozzi, Diego; Brotons-Mas, Jorge R; Cid, Elena; Tamas, Gabor; Menendez de la Prida, Liset

2017-06-21

Memory traces are reactivated selectively during sharp-wave ripples. The mechanisms of selective reactivation, and how degraded reactivation affects memory, are poorly understood. We evaluated hippocampal single-cell activity during physiological and pathological sharp-wave ripples using juxtacellular and intracellular recordings in normal and epileptic rats with different memory abilities. CA1 pyramidal cells participate selectively during physiological events but fired together during epileptic fast ripples. We found that firing selectivity was dominated by an event- and cell-specific synaptic drive, modulated in single cells by changes in the excitatory/inhibitory ratio measured intracellularly. This mechanism collapses during pathological fast ripples to exacerbate and randomize neuronal firing. Acute administration of a use- and cell-type-dependent sodium channel blocker reduced neuronal collapse and randomness and improved recall in epileptic rats. We propose that cell-specific synaptic inputs govern firing selectivity of CA1 pyramidal cells during sharp-wave ripples. Copyright © 2017 Elsevier Inc. All rights reserved.

[Convulsions due to an interaction between anti-epileptic drugs and rifampicin].

PubMed

Hanrath, Maarten A; Swart, Eleonora L

2014-01-01

Anti-epileptic drugs (AEDs) have a small therapeutic window, so it is important to monitor plasma levels. Inadequate plasma levels may lead to convulsions. Many AEDs are cleared hepatically, and there are many drug interactions that are known to lead to changes in plasma levels. A 54-year-old woman with known epilepsy developed convulsions after using rifampicin and flucloxacillin, despite the use of maintenance treatment in the form of carbamazepine, valproic acid and clonazepam. Since rifampicin is known to induce several cytochrome P450 enzymes and clearance of the anti-epileptic drug used may be affected by this, it can be assumed that the convulsions were caused by rifampicin. This interaction is however not mentioned in the Dutch 'G-standard' database. Rifampicin is known to be a strong inducer of various cytochrome P450 enzymes. This case description shows that the use of rifampicin may lead to convulsions. For this reason, these interactions should be included in the Dutch G-standard database.

The body comes to family therapy: Treatment of a school-aged boy with hyperventilation-induced non-epileptic seizures.

PubMed

Kozlowska, Kasia; Chudleigh, Catherine; Elliott, Bronwen; Landini, Andrea

2016-10-01

We present the case of a 10-year-old boy, Evan, where a knock to the head activated memories of past bullying, causing intense distress, activation of the body's stress-regulation systems and recurrent hospital presentations with hyperventilation-induced non-epileptic seizures. We describe the initial assessment session that enabled Evan and his family to understand the context for Evan's non-epileptic seizures, to engage with the therapeutic team and to collaborate in the implementation of a mind-body multimodal family-based intervention. Once the physical symptoms had been addressed therapeutically, we explored possible dangers within the family and school systems and we worked with Evan and his family to increase his ability to access comfort and protection from his parents. Our short hospital intervention highlighted the importance of ongoing therapeutic work with Evan and the family and laid the foundation stones for the next part of the family's therapeutic journey. © The Author(s) 2015.

The role of hypnosis in the detection of psychogenic seizures.

PubMed

Martínez-Taboas, Alfonso

2002-07-01

In this preliminary clinical investigation, hypnosis was used in the differential diagnosis of epileptic versus psychogenic seizures (PS). Eight patients with a clinical profile suggesting the presence of PS were given a hypnotic suggestion in which they had to go back in time to the exact moment of their last seizure. They were then asked to concentrate their attention on any unusual feeling or bodily sensation. All 8 patients presented a PS during the age regression protocol. In 6 cases, independent testimony from family members corroborated the morphological similarity of the induced attack and the ones presented in their natural environment. Also, the seizures ended abruptly after a command was given to stop them. A control group of 5 epileptic subjects did not present any signs of discomfort or seizure behavior during the hypnotic protocol. It is argued that a simple procedure as the one described in this investigation can be useful as a diagnostic tool in the differentiation of epileptic from PS attacks.

Cannabinoids, cannabinoid receptors and tinnitus.

PubMed

Smith, Paul F; Zheng, Yiwen

2016-02-01

One hypothesis suggests that tinnitus is a form of sensory epilepsy, arising partly from neuronal hyperactivity in auditory regions of the brain such as the cochlear nucleus and inferior colliculus. Although there is currently no effective drug treatment for tinnitus, anti-epileptic drugs are used in some cases as a potential treatment option. There is increasing evidence to suggest that cannabinoid drugs, i.e. cannabinoid receptor agonists, can also have anti-epileptic effects, at least in some cases and in some parts of the brain. It has been reported that cannabinoid CB1 receptors and the endogenous cannabinoid, 2-arachidonylglycerol (2-AG), are expressed in the cochlear nucleus and that they are involved in the regulation of plasticity. This review explores the question of whether cannabinoid receptor agonists are likely to be pro- or anti-epileptic in the cochlear nucleus and therefore whether cannabinoids and Cannabis itself are likely to make tinnitus better or worse. Copyright © 2015 Elsevier B.V. All rights reserved.

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

PubMed Central

Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

2012-01-01

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus PMID:21837247

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression.

PubMed

Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

2012-01-01

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA(A)) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus.

Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA (A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.

PubMed

Wu, Guofeng; Wang, Likun; Hong, Zhen; Ren, Siying; Zhou, Feng

2017-08-01

The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats). A stimulation electrode was implanted into the hippocampus of all of the rats. Hip-LFS was administered twice per day in the PRS group for two weeks. Simultaneously, amygdala stimulus-induced seizures and afterdischarge were recorded. After the hippocampal stimulation was terminated, the brain tissues were obtained to determine the GABA (A) receptors by a method of immumohistochemistry and a real-time polymerase chain reaction. The stages and duration of the amygdala stimulus-induced epileptic seizures were decreased in the PRS group. The afterdischarge threshold was increased and the duration as well as the afterdischarge frequency was decreased. Simultaneously, the GABA (A) expression was significantly increased in the PRS group. Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects of hippocampal stimulation may be partly achieved by increasing the GABA (A) receptor.

Perception and attitude to epilepsy among teachers in primary, secondary and tertiary educational institutions in middle belt Nigeria.

PubMed

Sanya, E O; Salami, T A T; Goodman, O O; Buhari, O I N; Araoye, M O

2005-07-01

Compared with the disability associated with repeated seizures or side-effects of antiepileptic medications, the social stigma associated with epilepsy is often a major handicap to people living with this condition. This study therefore looked at the knowledge, attitude and perception of teachers who see a lot of epileptics, relates on daily bases and have a high influence on students with epilepsy.Self-administered questionnaires were used to obtain information from 460 randomly selected teachers in primary, secondary and tertiary educational institutions in Kwara State-middle belt of Nigeria. The response rate was 75%. Almost all of the teachers had heard about epilepsy, but their awareness does not equate with the acceptance and understanding of epilepsy. About 30.5% believed that it could be contracted through the saliva of an epileptic, 27.7% thought it was synonymous with possession with evil spirit, while 10% misunderstood epilepsy for insanity. Close to one-fifth of the teachers were of the opinion that epileptic students have a below average mental capacity compared with other students and so cannot attainment the highest possible education. Negative attitude and bias towards epilepsy is still deeply ingrained among teachers in Nigeria. Apart from formal education, teachers need to have health education courses on common disease conditions such as epilepsy that are prevalent in school age. This might help to reduce prejudice and increase the acceptance of epileptic individuals into the classroom.

Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI.

PubMed

Pizzini, Francesca B; Farace, Paolo; Manganotti, Paolo; Zoccatelli, Giada; Bongiovanni, Luigi G; Golay, Xavier; Beltramello, Alberto; Osculati, Antonio; Bertini, Giuseppe; Fabene, Paolo F

2013-07-01

Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment. Copyright © 2013 Elsevier Inc. All rights reserved.

Reducing motion artifacts for long-term clinical NIRS monitoring using collodion-fixed prism-based optical fibers

PubMed Central

Yücel, Meryem A.; Selb, Juliette; Boas, David A.; Cash, Sydney S.; Cooper, Robert J.

2013-01-01

As the applications of near-infrared spectroscopy (NIRS) continue to broaden and long-term clinical monitoring becomes more common, minimizing signal artifacts due to patient movement becomes more pressing. This is particularly true in applications where clinically and physiologically interesting events are intrinsically linked to patient movement, as is the case in the study of epileptic seizures. In this study, we apply an approach common in the application of EEG electrodes to the application of specialized NIRS optical fibers. The method provides improved optode-scalp coupling through the use of miniaturized optical fiber tips fixed to the scalp using collodion, a clinical adhesive. We investigate and quantify the performance of this new method in minimizing motion artifacts in healthy subjects, and apply the technique to allow continuous NIRS monitoring throughout epileptic seizures in two epileptic in-patients. Using collodion-fixed fibers reduces the percent signal change of motion artifacts by 90 % and increases the SNR by 6 and 3 fold at 690 and 830 nm wavelengths respectively when compared to a standard Velcro-based array of optical fibers. The change in both HbO and HbR during motion artifacts is found to be statistically lower for the collodion-fixed fiber probe. The collodion-fixed optical fiber approach has also allowed us to obtain good quality NIRS recording of three epileptic seizures in two patients despite excessive motion in each case. PMID:23796546

Nap polygraphic recordings after partial sleep deprivation in patients with suspected epileptic seizures.

PubMed

Peraita-Adrados, R; Gutierrez-Solana, L; Ruiz-Falcó, M L; García-Peñas, J J

2001-02-01

A review of the literature shows that nap recordings make a significant contribution to epilepsy studies, providing evidence of specific EEG findings in patients suspected of having epilepsy. In addition, sleep deprivation can cause paroxysmal EEG activity and clinical seizures. We studied retrospectively 686 patients, 51.8% males and 48.2% females, who had experienced at least one episode classified from the clinical point of view as epileptic in origin. They were divided into six age groups. Patients underwent a two-hour (1 P.M.-3 P.M.) nap-video-polygraphic recording (EEG 13 channels using the standard 10-20 system, EOG, ECG, EMG and respiration), following a partial sleep deprivation (1 to 3 h) the night before. A second recording was made in 40 patients. In 35.3% of patients, a complete sleep cycle was obtained; in 64.6% sufficient light and deep NREM sleep was obtained, but not REM stage; in 9.3%, we only observed drowsiness and stage 1 of sleep, and this group was excluded from the analysis. Interictal and/or ictal epileptic discharges were observed during the first nap recording in 245 patients (40.4% of the sample). In addition, in 40 patients (11%) with normal or inconclusive first nap EEG, a second recording was able to demonstrate epileptic abnormalities in 35% of cases. Because of its good cost/benefit ratio and availability in most western laboratories, we consider the 'nap plus partial sleep deprivation' method as advantageous over other activation procedures.

[Tropical causes of epilepsy].

PubMed

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.

Epileptogenic developmental venous anomaly: insights from simultaneous EEG/fMRI.

PubMed

Scheidegger, Olivier; Wiest, Roland; Jann, Kay; König, Thomas; Meyer, Klaus; Hauf, Martinus

2013-04-01

Developmental venous anomalies (DVAs) are associated with epileptic seizures; however, the role of DVA in the epileptogenesis is still not established. Simultaneous interictal electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) recordings provide supplementary information to electroclinical data about the epileptic generators, and thus aid in the differentiation of clinically equivocal epilepsy syndromes. The main objective of our study was to characterize the epileptic network in a patient with DVA and epilepsy by simultaneous EEG/fMRI recordings. A 17-year-old woman with recently emerging generalized tonic-clonic seizures, and atypical generalized discharges, was investigated using simultaneous EEG/fMRI at the university hospital. Previous high-resolution MRI showed no structural abnormalities, except a DVA in the right frontal operculum. Interictal EEG recordings showed atypical generalized discharges, corresponding to positive focal blood oxygen level dependent (BOLD) correlates in the right frontal operculum, a region drained by the DVA. Additionally, widespread cortical bilateral negative BOLD correlates in the frontal and parietal lobes were delineated, resembling a generalized epileptic network. The EEG/fMRI recordings support a right frontal lobe epilepsy, originating in the vicinity of the DVA, propagating rapidly to both frontal and parietal lobes, as expressed on the scalp EEG by secondary bilateral synchrony. The DVA may be causative of focal epilepsies in cases where no concomitant epileptogenic lesions can be detected. Advanced imaging techniques, such as simultaneous EEG/fMRI, may thus aid in the differentiation of clinically equivocal epilepsy syndromes.

Paroxysmal events during prolonged video-video electroencephalography monitoring in refractory epilepsy.

PubMed

Sanabria-Castro, A; Henríquez-Varela, F; Monge-Bonilla, C; Lara-Maier, S; Sittenfeld-Appel, M

2017-03-16

Given that epileptic seizures and non-epileptic paroxysmal events have similar clinical manifestations, using specific diagnostic methods is crucial, especially in patients with drug-resistant epilepsy. Prolonged video electroencephalography monitoring during epileptic seizures reveals epileptiform discharges and has become an essential procedure for epilepsy diagnosis. The main purpose of this study is to characterise paroxysmal events and compare patterns in patients with refractory epilepsy. We conducted a retrospective analysis of medical records from 91 patients diagnosed with refractory epilepsy who underwent prolonged video electroencephalography monitoring during hospitalisation. During prolonged video electroencephalography monitoring, 76.9% of the patients (n=70) had paroxysmal events. The mean number of events was 3.4±2.7; the duration of these events was highly variable. Most patients (80%) experienced seizures during wakefulness. The most common events were focal seizures with altered levels of consciousness, progressive bilateral generalized seizures and psychogenic non-epileptic seizures. Regarding all paroxysmal events, no differences were observed in the number or type of events by sex, in duration by sex or age at onset, or in the number of events by type of event. Psychogenic nonepileptic seizures were predominantly registered during wakefulness, lasted longer, started at older ages, and were more frequent in women. Paroxysmal events recorded during prolonged video electroencephalography monitoring in patients with refractory epilepsy show similar patterns and characteristics to those reported in other latitudes. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

[The electroencephalographic correlates of neurological disorders in the late periods of exposure to ionizing radiation (the aftereffects of the accident at the Chernobyl Atomic Electric Power Station)].

PubMed

Zhavoronkova, L A; Kholodova, N B; Zubovskiĭ, G A; Smirnov, Iu N; Koptelov, Iu M; Ryzhov, N I

1994-01-01

EEG mapping and three-dimensional localization of epileptic activity sources together with a neurological analysis were carried out in subjects having taken part in 1986-1987 in the liquidation of consequences of the Chernobyl accident. Experimental group included 40 right-handed 25-45 years-old men having received a radiation dose of 15-51 Ber stated officially. Control group consisted of 20 healthy men. Neurological examination of the patients revealed vegetative-vascular and endocrine dysfunctions as well as diffuse neurological symptoms. EEG of one group of patients (25 persons) was characterized by slow alpha- and theta-band foci and epileptic waves in the central-frontal regions; epileptic sources were localized at the diencephalic level mainly in the midline being shifted to the right hemisphere. In the EEG of another group (15 persons) delta-waves were recorded in the frontal regions at the background of diffuse beta-activity. The sources of epileptic activity of a diffuse character were localized at the basal level of the brain and in the cortex (predominantly) in the left hemisphere. The results obtained together with SPECT mapping and CT data permit to suppose the organic damage of different brain structures (at the cortical and the midline levels) in the patients, with participation of diencephalic structures in the pathological process hypothalamic-hypophysial system being probably connected with adaptive processes in the CNS.

Epileptic encephalopathy with continuous spike-waves during sleep: the need for transition from childhood to adulthood medical care appears to be related to etiology.

PubMed

de Saint-Martin, Anne; Rudolf, Gabrielle; Seegmuller, Caroline; Valenti-Hirsch, Maria Paola; Hirsch, Edouard

2014-08-01

Epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) presents clinically with infrequent nocturnal focal seizures, atypical absences related to secondary bilateral synchrony, negative myoclonia, and atonic and rare generalized tonic-clonic seizures. The unique electroencephalography (EEG) pattern found in ECSWS consists of continuous, diffuse, bilateral spike-waves during slow-wave sleep. Despite the eventual disappearance of clinical seizures and EEG abnormalities by adolescence, the prognosis is guarded in most cases because of neuropsychological and behavioral deficits. ECSWS has a heterogeneous etiology (genetic, structural, and unknown). Because epilepsy and electroencephalography (EEG) abnormalities in epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) are self-limited and age related, the need for ongoing medical care and transition to adult care might be questioned. For adolescents in whom etiology remains unknown (possibly genetic) and who experience the disappearance of seizures and EEG abnormalities, there is rarely need for long-term neurologic follow-up, because often a relatively normal cognitive and social evolution follows. However, the majority of patients with structural and possibly "genetic syndromic" etiologies will have persistent cognitive deficits and will need suitable socioeducative care. Therefore, the transition process in ECSWS will depend mainly on etiology and its related features (epileptic active phase duration, and cognitive and behavioral evolution) and revolve around neuropsychological and social support rather than medical and pharmacologic follow-up. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model

PubMed Central

Choo, Brandon Kar Meng; Kundap, Uday P.; Kumari, Yatinesh; Hue, Seow-Mun; Othman, Iekhsan; Shaikh, Mohd Farooq

2018-01-01

Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate that O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ) treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish. PMID:29527169