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Absence Seizures (absence + seizures)
Selected AbstractsTypical versus Atypical Absence Seizures: Network Mechanisms of the Spread of ParoxysmsEPILEPSIA, Issue 8 2007Jose L. Perez Velazquez Summary: Purpose: Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike-and-wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures. Methods: We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired-pulse paradigm. Results: In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike-and-wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired-pulse depression was then found in hippocampus of rats that displayed atypical absence seizures. Conclusions: These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures. [source] fMRI of Brain Activation in a Genetic Rat Model of Absence SeizuresEPILEPSIA, Issue 6 2004Jeffrey R. Tenney Summary: Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level,dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure. [source] Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI AssessmentEPILEPSIA, Issue 9 2003Jeffrey R. Tenney Summary:,Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level,dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using ,-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike,wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [source] Tonic,Absence Seizures: An Underrecognized Seizure TypeEPILEPSIA, Issue 3 2003Tina T. Shih M.D. Summary: ,Purpose: The individual electroclinical patterns,tonic seizures with generalized paroxysmal fast activity (GPFA, activity >13 Hz), and absence seizures with generalized slow spike-and-wave activity (GSS&W, <3 Hz),have been extensively described in the literature. However, only passing reference was made to the pattern of GPFA followed by GSS&W. In addition, these descriptions were formulated in the pre-EMU (Epilepsy Monitoring Unit) era, without benefit of video/clinical correlation. We now characterize this underrecognized seizure type. Methods: We retrospectively reviewed the data from eight patients with seizures that demonstrated this stereotyped EEG and clinical pattern. Results: We identified eight patients (six female patients; age 6,29 years; age at seizure onset, neonate to 10 years) who were evaluated at the Columbia University Epilepsy Monitoring Units between 1993 and 2002. All eight had an International League Against Epilepsy (ILAE) diagnosis of symptomatic generalized epilepsy, with six of eight manifesting multiple seizure types, six of eight with mild static encephalopathy, and two with normal cognition. A total of 29 seizures of this pattern was recorded; 26 of 29 seizures demonstrated GPFA (frequency between 14 and 30 Hz, lasting 2,8 s) followed by GSS&W (frequency range between 1 and 2 Hz, lasting 3,50 s). The predominant clinical correlate was bilateral tonic activity followed by a period of inattentiveness. In general, these seizures were differentiated from the patient's typical tonic seizures by this protracted period of impaired attentiveness. Conclusions: We describe a heretofore underrecognized and poorly characterized seizure type in patients with symptomatic generalized epilepsy, which we have termed tonic,absence seizures. Clinically and electrographically, this consists of a tonic seizure with GPFA followed by an absence seizure with GSS&W. [source] Brain Sterols in the AY-9944 Rat Model of Atypical Absence SeizuresEPILEPSIA, Issue 1 2002Miguel A. Cortez Summary: ,Purpose: The AY-9944 (AY)-treated rat is a reproducible and clinically relevant animal model of atypical absence seizures. AY inhibits cholesterol synthesis, but the relation between brain sterol levels and the spontaneously recurrent absence seizures has not been determined. Methods: Long,Evans hooded rats were treated every 6 days from postnatal day (P)2 to P20 with AY (7.5 mg/kg, s.c.) or saline. Electrodes were permanently implanted under pentobarbital anesthesia at P50. Spike-and-wave discharge (SWD) duration and amplitude were quantified at P55. Changes in brain sterols after AY were examined in three different experiments, looking at brain regions (experiment 1), recovery after stopping AY (experiment 2), or gender differences (experiment 3). Results: Experiment 1: AY caused spontaneously recurrent slow SWD that lasted 59 times longer and had a 3.2-fold higher amplitude than that in controls. At P55, brain cholesterol was reduced and 7-dehydrocholesterol was increased in all brain regions (p < 0.0001). Experiment 2: Four hundred days after stopping AY-9944 treatment (P420), brain sterol levels had returned to normal levels, but the AY-induced SWD lasted twice as long as at P55. Experiment 3: At P55, AY-induced changes in plasma and liver (but not brain) sterols were significantly more severe in females compared with males. Conclusions: AY-induced seizures appear to be related to AY-induced changes in brain sterols but persisted long after the sterols had returned to normal after the last AY injection. Hence, there appears to be a critical developmental window during which the AY must be given but after which the AY-induced change in brain sterols is no longer essential to sustaining the seizures. [source] Absence Seizures Aggravated by Valproic AcidEPILEPSIA, Issue 7 2001Tally Lerman-Sagie Summary: ,Purpose: To report on pediatric patients with absence epilepsy who experienced absence seizure aggravation while receiving valproic acid (VPA). Methods: The charts of all children from four pediatric epilepsy clinics receiving VPA for absence epilepsy were reviewed. Patients were evaluated and followed up between 1994 and 2000. Results: Eight cases (six boys) of absence seizure aggravation were detected. Mean age at seizure onset was 5.8 years (range, 3,12 years). Six patients had simple absence seizures, one had myoclonic absences, and one had absences with automatisms. The electroencephalogram in all cases depicted generalized 3-Hz spike-and-wave activities. All eight patients experienced an increase in the frequency of absence seizures within days of VPA introduction. Dose increments resulted in further seizure aggravation. Serum levels of VPA were within therapeutic range in all patients. No case was attributed to VPA-induced encephalopathy. All patients improved on VPA discontinuation. In five children, VPA was reintroduced, resulting in further seizure aggravation. Conclusions: VPA can occasionally provoke absence seizure aggravation in patients with absence epilepsy. [source] Parental psychopathology and self-rated quality of life in adolescents with epilepsy in NigeriaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2006Abiodun O Adewuya MBChB This study sought to investigate the relationship between parental psychopathology and health-related quality of life in a group of Nigerian adolescents with epilepsy. The participants were 86 adolescents with epilepsy (50 males, 36 females; mean age 14y 5mo [SD 2y 1mo]; age range 12,18y). There were 54 (62.8%) adolescents with complex partial seizures, six (7.0%) with simple partial seizures, 14 (16.3%) with generalized tonic-clonic seizures, four (4.7%) with absence seizures, and eight (9.2%) with other types of seizure. They completed the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48). Parents also completed the General Health Questionnaire, Zung's Self-Rating Anxiety Scale, and Zung's Self-Rating Depressive Scale as measures of their psychopathology. Factors correlating with poor overall quality of life in the adolescents include longer duration of illness, large number of antiepileptic drugs, more severe medication toxicity, and psychopathology in the parents. General psychopathology in parents is significantly associated with QOLIE-AD-48 subscales of Epilepsy Impact (r= 0.527, p < 0.001), Attitude (r= 0.214, p= 0.047), Physical Function (r= 0.417, p < 0.001), Stigma (r= 0.305, p= 0.004), Social Support (r= 0.365, p= 0.001), and School Behaviour (r= 0.220, p= 0.042). There is a possibility of a cross-cultural difference on the effect of epilepsy on the quality of life of adolescents. Psychopathology in parents is significantly associated with poorer quality of life of these adolescents. Physicians should consider this, therefore, when planning intervention strategies in improving the quality of life in adolescents with epilepsy. [source] WAG/Rij rats show a reduced expression of CB1 receptors in thalamic nuclei and respond to the CB1 receptor agonist, R(+)WIN55,212-2, with a reduced incidence of spike-wave dischargesEPILEPSIA, Issue 8 2010Clementina M. Van Rijn Summary Purpose:, Genetically epileptic WAG/Rij rats develop spontaneous absence-like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB1) receptors. Methods:, Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of "presymptomatic" 2-month old and "symptomatic" 8-month-old WAG/Rij rats relative to age-matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB1 receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically injected with the potent CB1 receptor agonist, R(+)WIN55,212-2 (3,12 mg/kg, s.c.), given alone or combined with the CB1 receptor antagonist/inverse agonist, AM251 (12 mg/kg, s.c.). Results:, Data showed a reduction of CB1 receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB1 receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB1 receptor agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion:, These data indicate that the development of absence seizures is associated with plastic modifications of CB1 receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB1 receptors are targeted by novel antiabsence drugs. [source] Coexistence of symptomatic focal and absence seizures: Video-EEG and EEG-fMRI evidence of overlapping but independent epileptogenic networksEPILEPSIA, Issue 7 2009Serge Chassagnon Summary The distinction between typical absences and hypomotor seizures in patients having frontal lesions is difficult. In focal epilepsy, generalized-like interictal discharges can reflect either a coexistent generalized epileptic trait or a secondary bilateral synchrony. Using combined measures of the EEG and blood oxygenation level dependent (BOLD) activity, we studied a 50-year-old patient with both absence-like and symptomatic focal motor seizures. Focal activity induced activation in the lesional area and deactivation in the contralateral central cortex. Generalized spike-and-wave discharges (GSWDs) resulted also in perilesional activation, and multifocal symmetrical cortical and thalamic activations, and deactivation in associative cortical areas. Although the central cortex was involved during both types of epileptic activity, electroencephalography (EEG),functional magnetic resonance imaging (fMRI) revealed distinct neuronal networks at the time of the focal or generalized discharges, allowing a clear-cut differentiation of the generators. Whether the patient had distinct epileptic syndromes or distinct electrographic patterns from the lesional trigger remains debatable. [source] Monoamine variability in the chronic model of atypical absence seizuresEPILEPSIA, Issue 4 2009Eduard Bercovici Summary Purpose:, We studied the variability of the slow-spike-and-wave discharges (SSWDs) derived from AY-9944 (AY) treatment during brain development of Long-Evans hooded (LEh) rats. Methods:, Although all LEh rats received the standard dose of AY (7.5 mg/kg), we have observed an intersubject variability of the total SSWD duration at postnatal day (P) 55. Therefore, we set out to investigate the underlying brain levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and its metabolite (5-HIAA), as determined by high-performance liquid chromatography (HPLC) analyses from four different brain regions: thalamus (Th), frontoparietal cortex (Cx), hippocampus (Hp), and brainstem (Bs). Results:, All brains were obtained after two baseline electrocorticographic (ECoG) recordings with characteristic chronic, recurrent, bilaterally synchronous 4,6 Hz SSWD, at P 55 (336.25 ± 97.23 s/h) and P60 (494.50 ± 150.36 s) (r = 0.951, r2 = 0.904, p < 0.005, Pearson product). The thalamic NE levels and the brainstem NE, DA, and 5HT levels were all significantly correlated with baseline SSWD duration at P55 and P60 (p < 0.01, Pearson product). Conclusion:, Our data indicate that brain monoamine levels may determine the intersubject variability of SSWD duration in AY rats with chronic atypical absence seizures. [source] Audiogenic kindling in Wistar and WAG/Rij rats: Kindling-prone and kindling-resistant subpopulationsEPILEPSIA, Issue 10 2008Lyudmila V. Vinogradova Summary Purpose:, Audiogenic kindling (AK) is a model of naturally occurring epileptogenesis triggered by repeated sound stimulation of rats genetically prone to audiogenic seizures. It is accepted that limbic seizure networks underlie progressive changes in behavioral seizure pattern during AK. The present study investigated AK progression in rats susceptible and unsusceptible to absence seizures. Methods:, Progression of AK as indicated by an appearance and intensification of limbic clonus was examined in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats with genetic absence epilepsy and in Wistar rats. Results:, Subpopulations of kindling-prone and kindling-resistant rats were found in both Wistar and WAG/Rij strains. Despite identical seizure responses to the first sound stimulation, AK progression dramatically differed between the two subpopulations. AK-prone rats exhibited rapid kindling development up to maximal stage-5 severity. In AK-resistant rats, limbic clonus did not appear after 30 stimulations or if it appeared, it did not progress beyond stage 2. The proportions of AK-prone and AK-resistant animals within Wistar and WAG/Rij strains were similar. Comparison of Wistar and WAG/Rij rats within the kindling-prone and kindling-resistant groups did not reveal a significant strain effect on AK progression. However, within the WAG/Rij strain, a significantly higher incidence of absence seizures was found in AK-resistant rats compared to AK-prone rats. Conclusions:, The present study demonstrates that sensitivity to sound-induced epileptogenesis differs dramatically within Wistar and WAG/Rij strains, whereas genetic susceptibility to absence seizures does not change AK progression significantly. It is supposed that an increased incidence of nonconvulsive seizures and resistance to kindling result from a common seizure modulating mechanism. [source] Dense array EEG: Methodology and new hypothesis on epilepsy syndromesEPILEPSIA, Issue 2008Mark D. Holmes Summary Dense array EEG is a method of recording electroencephalography (EEG) with many more electrodes (up to 256) than is utilized with standard techniques that typically employ 19,21 scalp electrodes. The rationale for this approach is to enhance the spatial resolution of scalp EEG. In our research, dense array EEG is used in conjunction with a realistic model of head tissue conductivity and methods of electrographic source analysis to determine cerebral cortical localization of epileptiform discharges. In studies of patients with absence seizures, only localized cortical regions are involved during the attack. Typically, absences are accompanied by "wave,spike" complexes that show, both at the beginning and throughout the ictus, repetitive cycles of stereotyped, localized involvement of mainly mesial and orbital frontal cortex. Dense array EEG can also be used for long-term EEG video monitoring (LTM). We have used dense array EEG LTM to capture seizures in over 40 patients with medically refractory localization-related epilepsy, including both temporal and extra temporal cases, where standard LTM failed to reveal reliable ictal localization. One research goal is to test the validity of dense array LTM findings by comparison with invasive LTM and surgical outcome. Collection of a prospective series of surgical candidates who undergo both procedures is currently underway. Analysis of subjects with either generalized or localization-related seizures suggest that all seizures, including those traditionally classified as "generalized," propagate through discrete cortical networks. Furthermore, based on initial review of propagation patterns, we hypothesize that all epileptic seizures may be fundamentally corticothalamic or corticolimbic in nature. Dense array EEG may prove useful in noninvasive ictal localization, when standard methods fail. Future research will determine if the method will reduce the need for invasive EEG recordings, or assist in the appropriate placement of novel treatment devices. [source] Typical versus Atypical Absence Seizures: Network Mechanisms of the Spread of ParoxysmsEPILEPSIA, Issue 8 2007Jose L. Perez Velazquez Summary: Purpose: Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike-and-wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures. Methods: We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired-pulse paradigm. Results: In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike-and-wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired-pulse depression was then found in hippocampus of rats that displayed atypical absence seizures. Conclusions: These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures. [source] Nonepileptic Disorders Imitating Generalized Idiopathic EpilepsiesEPILEPSIA, Issue 2005Natalio Fejerman Summary:, Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic,clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed in Table 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening events in infants, cyanotic and pallid breath-holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages. Table 1. Nonepileptic disorders imitating idiopathic generalized epilepsies [source] Evidence for a Role of the Parafascicular Nucleus of the Thalamus in the Control of Epileptic Seizures by the Superior ColliculusEPILEPSIA, Issue 1 2005Karine Nail-Boucherie Summary:,Purpose: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. Methods: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a ,-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. Results: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. Conclusions: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy. [source] fMRI of Generalized Absence Status Epilepticus in Conscious Marmoset Monkeys Reveals Corticothalamic ActivationEPILEPSIA, Issue 10 2004Jeffrey R. Tenney Summary:,Purpose: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder. Methods: Adult male marmoset monkeys (Callithrix jacchus) were treated with ,-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike,wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level,dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. Results: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. Conclusions: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex. [source] fMRI of Brain Activation in a Genetic Rat Model of Absence SeizuresEPILEPSIA, Issue 6 2004Jeffrey R. Tenney Summary: Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level,dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure. [source] Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New-Onset Epilepsy: Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy SocietyEPILEPSIA, Issue 5 2004Jacqueline A. French Summary: Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. Results: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary. [source] Polygenic Control of Idiopathic Generalized Epilepsy Phenotypes in the Genetic Absence Rats from Strasbourg (GAERS)EPILEPSIA, Issue 4 2004Gabrielle Rudolf Summary: Purpose: Generalized nonconvulsive absence seizures are characterized by the occurrence of synchronous and bilateral spike-and-wave discharges (SWDs) on electroencephalographic recordings, concomitant with behavioral arrest. The GAERS (genetic absence rats from Strasbourg) strain, a well-characterized inbred model for idiopathic generalized epilepsy, spontaneously develops EEG paroxysms that resemble those of typical absence seizures. The purpose of this study was to investigate the genetic control of SWD variables by using a combination of genetic analyses and electrophysiological measurements in an experimental cross derived from GAERS and Brown Norway (BN) rats. Methods: SWD subphenotypes were quantified on EEG recordings performed at both 3 and 6 months in a cohort of 118 GAERS × BN F2 animals. A genome-wide scan of the F2 progenies was carried out with 146 microsatellite markers that were used to test each marker locus for evidence of genetic linkage to the SWD quantitative traits. Results: We identified three quantitative trait loci (QTLs) in chromosomes 4, 7, and 8 controlling specific SWD variables in the cross, including frequency, amplitude, and severity of SWDs. Age was a major factor influencing the detection of genetic linkage to the various components of the SWDs. Conclusions: The identification of these QTLs demonstrates the polygenic control of SWDs in the GAERS strain. Genetic linkages to specific SWD features underline the complex mechanisms contributing to SWD development in idiopathic generalized epilepsy. [source] Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI AssessmentEPILEPSIA, Issue 9 2003Jeffrey R. Tenney Summary:,Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level,dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using ,-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike,wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [source] Tonic,Absence Seizures: An Underrecognized Seizure TypeEPILEPSIA, Issue 3 2003Tina T. Shih M.D. Summary: ,Purpose: The individual electroclinical patterns,tonic seizures with generalized paroxysmal fast activity (GPFA, activity >13 Hz), and absence seizures with generalized slow spike-and-wave activity (GSS&W, <3 Hz),have been extensively described in the literature. However, only passing reference was made to the pattern of GPFA followed by GSS&W. In addition, these descriptions were formulated in the pre-EMU (Epilepsy Monitoring Unit) era, without benefit of video/clinical correlation. We now characterize this underrecognized seizure type. Methods: We retrospectively reviewed the data from eight patients with seizures that demonstrated this stereotyped EEG and clinical pattern. Results: We identified eight patients (six female patients; age 6,29 years; age at seizure onset, neonate to 10 years) who were evaluated at the Columbia University Epilepsy Monitoring Units between 1993 and 2002. All eight had an International League Against Epilepsy (ILAE) diagnosis of symptomatic generalized epilepsy, with six of eight manifesting multiple seizure types, six of eight with mild static encephalopathy, and two with normal cognition. A total of 29 seizures of this pattern was recorded; 26 of 29 seizures demonstrated GPFA (frequency between 14 and 30 Hz, lasting 2,8 s) followed by GSS&W (frequency range between 1 and 2 Hz, lasting 3,50 s). The predominant clinical correlate was bilateral tonic activity followed by a period of inattentiveness. In general, these seizures were differentiated from the patient's typical tonic seizures by this protracted period of impaired attentiveness. Conclusions: We describe a heretofore underrecognized and poorly characterized seizure type in patients with symptomatic generalized epilepsy, which we have termed tonic,absence seizures. Clinically and electrographically, this consists of a tonic seizure with GPFA followed by an absence seizure with GSS&W. [source] Resistance to Propagation of Amygdaloid Kindling Seizures in Rats with Genetic Absence EpilepsyEPILEPSIA, Issue 10 2002Esat E, kazan Summary: ,Purpose: The existence of absence epilepsy and temporal partial seizure pattern in the same patient is an uncommon state. In the present study, we aimed to evaluate whether the process of kindling as a model of complex partial seizures with secondary generalization is altered in rats with genetic absence epilepsy. Methods: Six- to 12-month-old nonepileptic control Wistar rats and genetic absence epileptic rats from Strasbourg (GAERS) were used in the experiments. One week before the experiments, bilateral stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and cortex, respectively. Animals were stimulated at their afterdischarge threshold current twice daily for the process of kindling and accepted as fully kindled after the occurrence of five grade 5 seizures. Bilateral EEGs from amygdala and cortex were recorded continuously during 20 min before and 40 min after each stimulus. Results: All control Wistar rats were fully kindled after stimulus 12 to 15. Although the maximal number of stimulations had been applied, GAERS remained at stage 2, and no motor seizures were observed. The afterdischarge duration in bilateral amygdala and the cortex after the kindling stimulus was shorter in GAERS when compared with control rats. Conclusions: Occurrence of only grade 2 seizures and no observation of grade 3,5 seizures in GAERS with the maximal number of stimulations would suggest that the generalized absence seizures may be the reason of the resistance in the secondary generalization of limbic seizures during amygdala kindling. [source] Mild Generalized Epilepsy and Developmental Disorder Associated with Large Inv Dup(15)EPILEPSIA, Issue 9 2002Rosanna Chifari Summary: ,Purpose: Several studies attempted to clarify the genotype,phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup(15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader,Willi/Angelman region. We report two patients with inv dup(15) who, in spite of a large duplication, had a mild phenotype including adult-onset epilepsy. This report may help to define the milder spectrum of the syndrome. Methods: A 25-year-old girl with mild mental retardation had a 6-year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike,wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27-year-old man with mild mental retardation, had a 5-year history of rare generalized tonic,clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video-EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control. Results: Molecular analysis revealed a large inv dup15 in both patients. Conclusions: The discrepancy between the mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear-cut etiology. [source] Clinical and Electrographic Features of Epileptic Spasms Persisting Beyond the Second Year of LifeEPILEPSIA, Issue 6 2002Márcio A. Sotero De Menezes Summary: ,Purpose: Few reports detailing the electroclinical features of epileptic spasms persisting beyond infancy have been published. We sought to characterize this unique population further. Methods: We retrospectively reviewed the clinical and video-EEG data on 26 patients (4,17 years; mean, 93 months) with a confirmed diagnosis of epileptic spasms and who were evaluated at our tertiary referral center between 1993 and 2000. Results: In half of our cases, epileptic spasms were associated with disorders of neuronal migration, severe perinatal asphyxia, and genetic anomalies. Interictal EEGs showed generalized slowing in the majority of patients, and a slow-wave transient followed by an attenuation of the background amplitude was the most common ictal EEG pattern associated with an epileptic spasm (19 cases). Other seizure types (number of cases in parentheses) included tonic seizures with or without a preceding spasm (13), partial seizures (11), myoclonic seizures (11), generalized tonic,clonic seizures (six), atypical absence seizures (two), and atonic seizures (one). Cases with a more organized EEG background (especially with frequencies ,7 Hz) were more likely to have better cognition. Continued disorganization of the EEG background and persistence of hypsarrhythmia were associated with poor developmental outcome. Conclusions: Patients with epileptic spasms persisting beyond age 2 years constitute a truly refractory population, one that should be better recognized by clinicians. Interestingly, although many therapies resulted in a >50% reduction in seizures, neither neurocognitive function nor quality of life was substantially improved with intervention. The interictal EEG background is the most helpful in predicting neurologic outcome. [source] Brain Sterols in the AY-9944 Rat Model of Atypical Absence SeizuresEPILEPSIA, Issue 1 2002Miguel A. Cortez Summary: ,Purpose: The AY-9944 (AY)-treated rat is a reproducible and clinically relevant animal model of atypical absence seizures. AY inhibits cholesterol synthesis, but the relation between brain sterol levels and the spontaneously recurrent absence seizures has not been determined. Methods: Long,Evans hooded rats were treated every 6 days from postnatal day (P)2 to P20 with AY (7.5 mg/kg, s.c.) or saline. Electrodes were permanently implanted under pentobarbital anesthesia at P50. Spike-and-wave discharge (SWD) duration and amplitude were quantified at P55. Changes in brain sterols after AY were examined in three different experiments, looking at brain regions (experiment 1), recovery after stopping AY (experiment 2), or gender differences (experiment 3). Results: Experiment 1: AY caused spontaneously recurrent slow SWD that lasted 59 times longer and had a 3.2-fold higher amplitude than that in controls. At P55, brain cholesterol was reduced and 7-dehydrocholesterol was increased in all brain regions (p < 0.0001). Experiment 2: Four hundred days after stopping AY-9944 treatment (P420), brain sterol levels had returned to normal levels, but the AY-induced SWD lasted twice as long as at P55. Experiment 3: At P55, AY-induced changes in plasma and liver (but not brain) sterols were significantly more severe in females compared with males. Conclusions: AY-induced seizures appear to be related to AY-induced changes in brain sterols but persisted long after the sterols had returned to normal after the last AY injection. Hence, there appears to be a critical developmental window during which the AY must be given but after which the AY-induced change in brain sterols is no longer essential to sustaining the seizures. [source] Absence Seizures Aggravated by Valproic AcidEPILEPSIA, Issue 7 2001Tally Lerman-Sagie Summary: ,Purpose: To report on pediatric patients with absence epilepsy who experienced absence seizure aggravation while receiving valproic acid (VPA). Methods: The charts of all children from four pediatric epilepsy clinics receiving VPA for absence epilepsy were reviewed. Patients were evaluated and followed up between 1994 and 2000. Results: Eight cases (six boys) of absence seizure aggravation were detected. Mean age at seizure onset was 5.8 years (range, 3,12 years). Six patients had simple absence seizures, one had myoclonic absences, and one had absences with automatisms. The electroencephalogram in all cases depicted generalized 3-Hz spike-and-wave activities. All eight patients experienced an increase in the frequency of absence seizures within days of VPA introduction. Dose increments resulted in further seizure aggravation. Serum levels of VPA were within therapeutic range in all patients. No case was attributed to VPA-induced encephalopathy. All patients improved on VPA discontinuation. In five children, VPA was reintroduced, resulting in further seizure aggravation. Conclusions: VPA can occasionally provoke absence seizure aggravation in patients with absence epilepsy. [source] Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y2 receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Margaret J. Morris Abstract Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y-receptor subtype(s) on which NPY exerts this anti-absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90-min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype-selective agonists of Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu28,31]NPY24,36, 3 nmol), Y5 receptors [hPP1,17,Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y1 (BIBP3226, 20 nmol), Y2 (BIIE0246, 20 nmol) and Y5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1 - and Y5 -selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 agonist, while significant increases in food intake were seen following NPY and the other Y-subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation. [source] Environmental manipulations early in development alter seizure activity, Ih and HCN1 protein expression later in lifeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Ulrich Schridde Abstract Although absence epilepsy has a genetic origin, evidence from an animal model (Wistar Albino Glaxo/Rijswijk; WAG/Rij) suggests that seizures are sensitive to environmental manipulations. Here, we show that manipulations of the early rearing environment (neonatal handling, maternal deprivation) of WAG/Rij rats leads to a pronounced decrease in seizure activity later in life. Recent observations link seizure activity in WAG/Rij rats to the hyperpolarization-activated cation current (Ih) in the somatosensory cortex, the site of seizure generation. Therefore, we investigated whether the alterations in seizure activity between rats reared differently might be correlated with changes in Ih and its channel subunits hyperpolarization-activated cation channel HCN1, 2 and 4. Whole-cell recordings from layer 5 pyramidal neurons, in situ hybridization and Western blot of the somatosensory cortex revealed an increase in Ih and HCN1 in neonatal handled and maternal deprived, compared to control rats. The increase was specific to HCN1 protein expression and did not involve HCN2/4 protein expression, or mRNA expression of any of the subunits (HCN1, 2, 4). Our findings provide the first evidence that relatively mild changes in the neonatal environment have a long-term impact of absence seizures, Ih and HCN1, and suggest that an increase of Ih and HCN1 is associated with absence seizure reduction. Our findings shed new light on the role of Ih and HCN in brain functioning and development and demonstrate that genetically determined absence seizures are quite sensitive for early interventions. [source] The influence of strain and housing on two types of spike-wave discharges in ratsGENES, BRAIN AND BEHAVIOR, Issue 1 2004U. Schridde WAG/Rij rats, a genetic model of absence epilepsy, show two types of spike-wave discharges (Type 1 and Type 2) in their EEG activity. The large interindividual variation in the expression of the phenotypes (number and mean duration of spike-wave discharges) suggests that as well as genetic, environmental factors also play a role. The aim of our study was to establish effects of strain and housing on the incidence and expression of both types of paroxysms. Therefore, WAG/Rij and ACI rats were housed from weaning in either an enriched or impoverished environment for 60 days. At three months of age the EEG of the rats was recorded for four hours to examine the effects of strain and housing on the incidence and expression of the two types of paroxysms. Generally, enriched housing led to worsening of Type 1 and Type 2 spike-wave discharges (SWD). However, the number of affected rats and the expression (number and mean duration) of Type 1 and Type 2 spike-wave discharges were differently influenced by strain and housing. This suggests that Type 1 and Type 2 spike-wave discharges are independent phenomena and that number and mean duration of these paroxysms are controlled by different mechanisms. Finally, the worsening of absence seizures after enrichment is different from what has been found for convulsive seizures. [source] Anticonvulsant activities of nutmeg oil of Myristica fragransPHYTOTHERAPY RESEARCH, Issue 2 2009Abdul Wahab Abstract The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experiments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not induce motor impairment when tested up to 600 µL/kg in the inverted screen acute neurotoxicity test. Furthermore, the LD50 (2150 µL/kg) value was much higher than its anticonvulsant doses (50,300 µL/kg). The results indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the treatment of myoclonic and absence seizures. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||