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Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures  [PDF]
A. S. Bazyan,G. van Luijtelaar
ISRN Neurology , 2013, DOI: 10.1155/2013/875834
Abstract: The absence epilepsy typical electroencephalographic pattern of sharp spikes and slow waves (SWDs) is considered to be due to an interaction of an initiation site in the cortex and a resonant circuit in the thalamus. The hyperpolarization-activated cyclic nucleotide-gated cationic Ih pacemaker channels (HCN) play an important role in the enhanced cortical excitability. The role of thalamic HCN in SWD occurrence is less clear. Absence epilepsy in the WAG/Rij strain is accompanied by deficiency of the activity of dopaminergic system, which weakens the formation of an emotional positive state, causes depression-like symptoms, and counteracts learning and memory processes. It also enhances GABAA receptor activity in the striatum, globus pallidus, and reticular thalamic nucleus, causing a rise of SWD activity in the cortico-thalamo-cortical networks. One of the reasons for the occurrence of absences is that several genes coding of GABAA receptors are mutated. The question arises: what the role of DA receptors is. Two mechanisms that cause an infringement of the function of DA receptors in this genetic absence epilepsy model are proposed. 1. Introduction Absence seizures, typical for many different patients with absence epilepsy, principally differ from convulsive seizures. To illustrate, a number of widely used and efficient anticonvulsant drugs enhance absence seizures in patients and in the genetic absence models and ethosuximide is only effective in suppressing absence seizures and completely ineffective in other types of seizures [1–3]. Absence epilepsy is characterized by the occurrence of spontaneous occurring spike-wave discharges (SWDs) and periods of reduced alertness or responsiveness. The SWDs are induced by hyperpolarization and they appear on an otherwise normal EEG. The spike of the SWD represents an excitatory postsynaptic potential and bursts of action potentials (Figure 1(b)) of thalamocortical and corticothalamic cells, the wave a slow wave in the EEG, is the subsequent inhibitory phase [4, 5]. The generalized and widespread bilaterally synchronous SWDs are the result of highly synchronized oscillations in corticothalamocortical networks. SWDs, as can be found in WAG/Rij rats, have a local cortical origin in the perioral region of the somatosensory cortex [6–12], which is now confirmed in GAERS [13, 14], another well validated and often used strain of rats with absence epilepsy [15, 16]. Local injections in the perioral region of the somatosensory cortex of the T-type Ca2+ channel blocker ethosuximide was rather effective in suppressing
Lack of appropriate controls leads to mistaking absence seizures for post-traumatic epilepsy  [PDF]
Krista M. Rodgers,F. Edward Dudek,Daniel S. Barth
Quantitative Biology , 2015,
Abstract: Here we provide a thorough discussion of a rebuttal by D'Ambrosio et al to a study conducted by Rodgers et al. (Rodgers KM, Dudek FE, Barth DS (2015) Progressive, Seizure-Like, Spike- Wave Discharges Are Common in Both Injured and Uninjured Sprague-Dawley Rats: Implications for the Fluid Percussion Injury Model of Post-Traumatic Epilepsy. J Neurosci. 35(24):9194-204. doi: 10.1523/JNEUROSCI.0919-15.2015.) to investigate focal seizures and acquired epileptogenesis induced by head injury in the rat. This manuscript serves as supplementary document for our letter to the Editor to appear in the Journal of Neuroscience. We find the rebuttal is flawed on all points, particularly concerning use of proper controls, experimental methods, analytical methods, and epilepsy diagnostic criteria, leading to mistaking absence seizures for post-traumatic epilepsy.
Unraveling Genetic Modifiers in the Gria4 Mouse Model of Absence Epilepsy  [PDF]
Wayne N. Frankel ,Connie L. Mahaffey,Tracy C. McGarr,Barbara J. Beyer,Verity A. Letts
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004454
Abstract: Absence epilepsy (AE) is a common type of genetic generalized epilepsy (GGE), particularly in children. AE and GGE are complex genetic diseases with few causal variants identified to date. Gria4 deficient mice provide a model of AE, one for which the common laboratory inbred strain C3H/HeJ (HeJ) harbors a natural IAP retrotransposon insertion in Gria4 that reduces its expression 8-fold. Between C3H and non-seizing strains such as C57BL/6, genetic modifiers alter disease severity. Even C3H substrains have surprising variation in the duration and incidence of spike-wave discharges (SWD), the characteristic electroencephalographic feature of absence seizures. Here we discovered extensive IAP retrotransposition in the C3H substrain, and identified a HeJ-private IAP in the Pcnxl2 gene, which encodes a putative multi-transmembrane protein of unknown function, resulting in decreased expression. By creating new Pcnxl2 frameshift alleles using TALEN mutagenesis, we show that Pcnxl2 deficiency is responsible for mitigating the seizure phenotype – making Pcnxl2 the first known modifier gene for absence seizures in any species. This finding gave us a handle on genetic complexity between strains, directing us to use another C3H substrain to map additional modifiers including validation of a Chr 15 locus that profoundly affects the severity of SWD episodes. Together these new findings expand our knowledge of how natural variation modulates seizures, and highlights the feasibility of characterizing and validating modifiers in mouse strains and substrains in the post-genome sequence era.
Juvenile myoclonic epilepsy
Alfradique, Isabel;Vasconcelos, Marcio Moacyr;
Arquivos de Neuro-Psiquiatria , 2007, DOI: 10.1590/S0004-282X2007000700036
Abstract: juvenile myoclonus epilepsy (jme) is a common epileptic syndrome, the etiology of which is genetically determined. its onset occurs from 6 through 22 years of age, and affected patients present with myoclonic jerks, often associated with generalized tonic-clonic seizures - the most common association - and absence seizures. jme is non-progressive, and there are no abnormalities on clinical examination or intellectual deficits. psychiatric disorders may coexist. generalized polyspike-and-waves are the most characteristic electroencephalographic pattern. usual neuroimaging studies show no abnormalities. atypical presentations should be entertained, as they are likely to induce misdiagnosis. prevention of precipitating factors and therapy with valproic acid (vpa) are able to control seizures in the great majority of patients. whenever vpa is judged to be inappropriate, other antiepileptic drugs such as lamotrigine may be considered. treatment should not be withdrawn, otherwise recurrences are frequent.
Absence Seizures
H Ehsani
Iranian Journal of Pediatrics , 1986,
Abstract: Presenting two patients with typical absence seizures this paper discusses the clinical features, diagnostic tests and therapeutic possibilities of the disease. Absence seizures may have various clinical pictures. Early recognition and treatment may prevent avoidable complications and sequelae. Otherwise the prognostic outcome is poor. In addition to clinical observation, EEG is the most helpful diagnostic means. This shows characteristic changes especially under stimulation by hyperventilation. Ethosuximide is the drug of choice in the therapy of absence seizures, which causes the clinical symptoms as well as EEG changes to disappear.
Epilepsy in patients with psychogenic non-epileptic seizures
Marchetti, Renato Luiz;Kurcgant, Daniela;Gallucci-Neto, José;Von Bismark, Mary Ann;Fiore, Lia Arno;
Arquivos de Neuro-Psiquiatria , 2010, DOI: 10.1590/S0004-282X2010000200003
Abstract: the aim of this study was to evaluate the frequency of epilepsy in patients who presented psychogenic non-epileptic seizures (pnes). the evaluation was carried out during intensive veeg monitoring in a diagnostic center for epilepsy in a university hospital. the difficulties involved in reaching this diagnosis are discussed. ninety-eight patients underwent intensive and prolonged video-electroencephalographic (veeg) monitoring; out of these, a total of 28 patients presented pnes during monitoring. epilepsy was defined as present when the patient presented epileptic seizures during veeg monitoring or when, although not presenting epileptic seizures during monitoring, the patient presented unequivocal interictal epileptiform discharges. the frequency of epilepsy in patients with pnes was 50% (14 patients). our findings suggest that the frequency of epilepsy in patients with pnes is much higher than that of previous studies, and point out the need, at least in some cases, for prolonging the evaluation of patients with pnes who have clinical histories indicating epilepsy.
Atypical EEG pattern in children with absence seizures
Silva, Délrio F.;Lima, Márcia Marques;Anghinah, Renato;Zanoteli, Edmar;Lima, José Geraldo Camargo;
Arquivos de Neuro-Psiquiatria , 1995, DOI: 10.1590/S0004-282X1995000200012
Abstract: we studied four children with diagnosis of absence seizures (generalized primary epilepsy), and with a generalized delta activity on the eeg during clinical attacks provoked by hyperventilation. the lack of ictal generalized spike-and-wave discharges with a frequency of 3 hz in our patients, makes this an atypical pattern. all children had complete control of their seizures and disappearance of the eeg changes with valproate. we concluded that generalized delta activity observed on eeg during the hyperventilation in children should not always be considered as a normal finding for age, since it could be an ictal event of an absence seizure.
Clinical and EEG Analysis of Patients With Idiopathic Generalized Epilepsy and Photosensitivity  [PDF]
Nazl? DEM?RKAYA,Ebru Nur VANLI YAVUZ,Ebru ALTINDA?,Betul BAYKAN
Journal of Neurological Sciences , 2009,
Abstract: Introduction: Our aim is to define the electroclinical characteristics of patients with photosensitive idiopathic generalized epilepsy (IGE) and to investigate the differences in seizure types, therapy and outcome between subgroups, based on photoparoxysmal response (PPR)/EEG characteristics and different syndromes.Patients and Methods: Fifty consecutive patients with a diagnosis of IGE and having EEG or clinical evidence for photosensitivity have been identified from the epilepsy outpatient clinic database of the Department of Neurology (Istanbul Medical Faculty, Istanbul University). Clinical and EEG data was collected retrospectively.Results: Thirty-six female and 14 male patients with median age 25.5 (14-63) were included to the study. The juvenile myoclonic epilepsy (JME) subgroup (n:24) had a significantly higher current age (p=0.035) and age at onset of seizures (p=0.029) compared with the absence epilepsy (AE) (n:12). Sleep deprivation triggers the seizures significantly more often in the JME subgroup compared with AE (p=0.003). Seizure records during EEG significantly more often in patients with AE (p=0.016). Patients with prolonged PPRs experienced significantly more clinical seizures during an EEG recording than patients with self-limited PPRs (p=0.000). The patients who were not seizure free had significantly more absence seizures (AS) (initially) compared with the patients who became seizure free (p=0.001).Conclusion: Our findings in a retrospective cohort suggest that having AS is a negative prognostic factor for the seizure outcome in patients with photosensitive IGE.
Ontology and Knowledge Management System on Epilepsy and Epileptic Seizures  [PDF]
Pedro Almeida,Paulo Gomes,Francisco Sales,Ana Nogueira,António Dourado
Computer Science , 2010,
Abstract: A Knowledge Management System developed for supporting creation, capture, storage and dissemination of information about Epilepsy and Epileptic Seizures is presented. We present an Ontology on Epilepsy and a Web-based prototype that together create the KMS.
Guidelines for epilepsy management in India classification of seizures and epilepsy syndromes
Ramaratnam Sridharan,Satishchandra P
Annals of Indian Academy of Neurology , 2010,
Abstract: This article is part of the Guidelines for Epilepsy management in India. This article reviews the classification systems used for epileptic seizures and epilepsy and present the recommendations based on current evidence. At present, epilepsy is classified according to seizure type and epilepsy syndrome using the universally accepted International League Against Epilepsy (ILAE) classification of epileptic seizures and epilepsy syndromes. A multi-axial classification system incorporating ictal phenomenology, seizure type, epilepsy syndrome, etiology and impairments is being developed by the ILAE task force. The need to consider age-related epilepsy syndromes is particularly important in children with epilepsy. The correct classification of seizure type and epilepsy syndrome helps the individual with epilepsy to receive appropriate investigations, treatment, and information about the likely prognosis.
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