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Objectives: Absence seizures impair psychosocial function, yet their detailed neuronal basis remains unknown. Recent work in a rat model suggests that cortical arousal state changes prior to seizures and that single neurons show diverse firing patterns during seizures. Our aim was to extend these investigations to a mouse model with studies of neuronal activity and arousal state to facilitate future fundamental investigations of absence epilepsy., Methods: We performed in vivo extracellular single unit recordings on awake head-fixed C3H/HeJ mice. Mice were implanted with tripolar electrodes for cortical electroencephalography (EEG). Extracellular single unit recordings were obtained with glass micropipettes in the somatosensory barrel cortex, while animals ambulated freely on a running wheel. Signals were digitized and analyzed during seizures and at baseline., Results: Neuronal activity was recorded from 36 cortical neurons in 19 mice while EEG showed characteristic 7-8 Hz spike-wave discharges. Different single neurons showed distinct firing patterns during seizures, but the overall mean population neuronal firing rate during seizures was no different from pre-seizure baseline. However, the rhythmicity of neuronal firing during seizures was significantly increased (p < 0.001). In addition, beginning 10s prior to seizure initiation, we observed a progressive decrease in cortical high frequency (>40 Hz) EEG and an increase in lower frequency (1-39 Hz) activity suggesting decreased arousal state., Significance: We found that the awake head-fixed C3H/HeJ mouse model demonstrated rhythmic neuronal firing during seizures, and a decreased cortical arousal state prior to seizure onset. Unlike the rat model we did not observe an overall decrease in neuronal firing during seizures. Similarities and differences across species strengthen the ability to investigate fundamental key mechanisms. Future work in the mouse model will identify the molecular basis of neurons with different firing patterns, their role in seizure initiation and behavioral deficits, with ultimate translation to human absence epilepsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Childhood absence epilepsy is one of the most prevalent pediatric epilepsy syndromes, but diagnostic delay is common and consequential. Childhood absence epilepsy is diagnosed by history and physical examination including hyperventilation with electroencephalography (EEG) used to confirm the diagnosis. Hyperventilation produces generalized spike-wave discharges on EEG in >90% of patients with childhood absence epilepsy and provokes clinical absence seizures consisting of brief loss of consciousness typically within 90 seconds. Child neurologists report a high volume of referrals for children with "staring spells" that strain already limited health care resources. Resources are further strained by the use of EEG for monitoring antiseizure medication effectiveness with unclear benefit. In this review, we examine the safety and efficacy of hyperventilation activation as a tool for the diagnosis and management of childhood absence seizures., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico-thalamo-cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited Pvalb -tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Abdelaal et al.)

The persistence of typical absence seizures (AS) in adolescence and adulthood may reduce the quality of life of patients with genetic generalized epilepsies (GGEs). The prevalence of drug resistant AS is probably underestimated in this patient population, and treatment options are relatively scarce. Similarly, atypical absence seizures in developmental and epileptic encephalopathies (DEEs) may be unrecognized, and often persist into adulthood despite improvement of more severe seizures. These two seemingly distant conditions, represented by typical AS in GGE and atypical AS in DEE, share at least partially overlapping pathophysiological and genetic mechanisms, which may be the target of drug and neurostimulation therapies. In addition, some patients with drug-resistant typical AS may present electroclinical features that lie in between the two extremes represented by these generalized forms of epilepsy., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The establishment of a recent theoretical model of a coupled cortical thalamic network is an important step in the spatiotemporal dynamics of the brain. However, choosing the coupling distances and parameters for deep brain stimulation remains a very challenging task. This study aimed to establish a coupled cortical thalamic model with uncertain coupling distances. Utilizing different pathways formed by the pyramidal neuronal population, thalamic reticular nucleus, and thalamic relay nucleus, we reduced epileptic seizures with spike-wave discharges (SWDs) at 2-4 Hz. In modelling terms, numerical simulations demonstrated that a combination (1/3, 1/9) of the left and right ventricles is the optimal coupling distance of the proposed model by analyzing the percentage of SWDs. In simulation terms, on the one hand, the number of SWDs is inversely proportional to the amplitude; on the other hand, the number of SWDs shows a U-shaped trend with the change in frequency. The present study provides an important theoretical basis and direction for the future treatment of absence epilepsy. In brief, our simulation results will hopefully provide some help to patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: When performed correctly, hyperventilation (HV) for three minutes provokes absence seizures in virtually all children, a finding suggestive of a diagnosis of childhood absence epilepsy (CAE). Interestingly, some children experience absence seizures while performing HV in the office yet do not experience absences during HV on subsequent routine EEG. In most instances, HV during routine EEG is performed in the supine position, while in the office HV is done with the child sitting-up. Therefore, we hypothesized that the position in which HV is performed may influence its yield in provoking absence seizures., Methods: We conducted a randomized multi-center controlled trial among children (4-10 years old) with suspected CAE. During a routine EEG, children were asked to perform HV twice, in the supine and sitting positions., Results: Twenty children (four males) diagnosed with CAE were included in the analysis. Seventeen of the 20 patients experienced absence seizures while sitting and 13 experienced seizures during supine HV (p = 0.031). All patients that had absence seizures during supine HV also had seizures during sitting HV. Among patients with absences in both positions, seizure duration was significantly shorter during sitting HV (mean 8.69 seconds) than during supine HV (mean 12 seconds) (p = 0.042). An opposite tendency was seen in the younger age group (4-7 years), with shorter seizures in the supine HV group (5.6 seconds supine, 7.57 seconds sitting, p = 0.019)., Conclusions: HV in the sitting position may increase the yield of provoking absence seizures during routine EEGs, thereby improving its sensitivity in the diagnosis of CAE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Hyperventilation (HV) in children can lead to HV-induced high-amplitude rhythmic slowing (HIHARS) on the EEG (electroencephalogram) which is sometimes associated with altered awareness (AA) and concomitant semiological features. Our aims were to determine the frequency of HIHARS in children, to assess if the associated semiological features were temporally related to HV, and to evaluate if specific semiological features can differentiate HIHARS with AA from absence seizures., Methods: Consecutive children with suspected new onset seizure(s) underwent HV and awareness testing during video-EEG acquisition. Hyperventilation-induced high-amplitude rhythmic slowing was defined as 2.5- to 5-Hz generalized rhythmic slowing with amplitude ≥100 μv lasting for ≥3 s. The associated semiological features were compared between the group of children with HIHARS and AA, an age- and gender-matched control group without HIHARS, and in children who experienced absence seizures during HV., Results: One hundred sixteen children with a mean age of 9.8 years were included. Hyperventilation-induced high-amplitude rhythmic slowing occurred in 39 children (33.6%) with AA documented in 30 (76.9%). The probability of developing AA during HIHARS was significantly and positively correlated with the HIHARS duration. The frequencies of HIHARS were not significantly different between children diagnosed with seizure(s) and those with nonepileptic spells. Hyperventilation cessation and staring did not occur in any child of the control group. Fidgeting and yawning were significantly more common in the group with HIHARS with AA while staring and blinking were significantly more frequent in the group of children with absence seizures., Conclusions: We ascertained that HIHARS with AA is a relatively common occurrence in children and most likely represents an age-related nonepileptic phenomenon. When associated with fidgeting or yawning, it can help differentiate this phenomenon from absence seizures. However, recording the concomitant presence of generalized spike wave discharges on the EEG remains essential to confirm the diagnosis of absence seizures., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A single injection of the cannabinoid agonist R(+)WIN55,212-2 (WIN) is known to cause an increase of the mean duration of spontaneously occurring spike-and-wave discharges (SWDs) in rats of the WAG/Rij strain, a genetic model for absence epilepsy. The aim of the present study was to establish whether repeated activation of CB 1 receptors with WIN leads to tolerance in its effect on SWD parameters, spectral density, and behavior over time. Adult male WAG/Rij rats (n = 16) were treated with WIN (6 mg/kg) or vehicle (olive oil). Injections (s.c.) took place 3 times per week during 2 weeks. Electroencephalogram (EEG) recordings, each lasting 24 h, were made 3 times: immediately before the first injection (baseline), immediately after the first injection (acute treatment), and after 2 weeks of treatment (subchronic treatment). The recordings were analyzed regarding incidence, durations of SWDs, and hazard rates of the durations of SWDs, the latter to describe SWD stopping probabilities. Putative changes in the spectral content of the EEG before and after WIN during active and passive behaviors were additionally investigated. Spike-and-wave discharge incidence was not affected by the acute and subchronic treatments. The mean duration of the SWDs was significantly longer than controls in the acute WIN-treated animals [11.9-s standard error of the mean (SEM): 0.64 compared with 8.4-s SEM: 0.25] as well as in subchronically treated animals (11.5-s SEM: 1.00 compared with 8.4-s SEM: 0.25). Hazard rates were significantly lower for WIN-treated animals at SWD durations in the 5.04-20.16-s range on both occasions. No effects of WIN on the frequency spectrum of the ongoing EEG were found, neither acutely nor after repeated administration. Evidence for tolerance was not found. The results on the mean duration and hazard rates suggest that stimulating the endocannabinoid system affects the SWD stopping mechanism, resulting in more long SWDs. We speculate that this effect is likely to be a direct result of CB 1 receptor agonism and a subsequent decrease in the availability of gamma-aminobutyric acid (GABA) in the reticular thalamic nucleus, which further weakens, in WAG/Rij rats already disturbed, the stopping mechanism of the SWDs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Generalized spike-wave discharges (SWDs) are the hallmark of generalized epilepsy on the electroencephalogram (EEG). In clinically obvious cases, generalized SWDs produce myoclonic, atonic/tonic, or absence seizures with brief episodes of staring and behavioral unresponsiveness. However, some generalized SWDs have no obvious behavioral effects. A serious challenge arises when patients with no clinical seizures request driving privileges and licensure, yet their EEG shows generalized SWD. Specialized behavioral testing has demonstrated prolonged reaction times or missed responses during SWD, which may present a driving hazard even when patients or family members do not notice any deficits. On the other hand, some SWDs are truly asymptomatic in which case driving privileges should not be restricted. Clinicians often decide on driving privileges based on SWD duration or other EEG features. However, there are currently no empirically-validated guidelines for distinguishing generalized SWDs that are "safe" versus "unsafe" for driving. Here, we review the clinical presentation of generalized SWD and recent work investigating mechanisms of behavioral impairment during SWD with implications for driving safety. As a future approach, computational analysis of large sets of EEG data during simulated driving utilizing machine learning could lead to powerful methods to classify generalized SWD as safe vs. unsafe. This may ultimately provide more objective EEG criteria to guide decisions on driving safety in people with epilepsy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Sunflower Syndrome describes reflex seizures - typically eyelid myoclonia with or without absence seizures - triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients., Methods: Search of the electronic medical record and EEG database, as well as survey of epilepsy providers at our institution, yielded 13 cases of Sunflower Syndrome between 2002 and 2017. We reviewed the records and EEG tracings., Results: Patients were mostly young females, with an average age of onset of 5.5 years. Seven had intellectual, attentional or academic problems. Self-induced seizures were predominantly eyelid myoclonia ± absences and 6 subjects also had spontaneous seizures. EEG demonstrated a normal background with 3-4 Hz spike waves ± polyspike waves as well as a photoparoxysmal response. Based on both clinical and EEG response, valproate was the most effective treatment for reducing or eliminating seizures and improving the EEG; 9 patients tried valproate and 66% had significant improvement or resolution of seizures. None of the nine patients on levetiracetam or seven patients on lamotrigine monotherapy achieved seizure control, though three patients had improvement with polypharmacy., Conclusions: Valproate monotherapy continues to be the most effective treatment for Sunflower Syndrome and should be considered early. For patients who cannot tolerate valproate, higher doses of lamotrigine or polypharmacy should be considered. Levetiracetam monotherapy, even at high doses, is unlikely to be effective., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To elucidate the characteristics of the myoclonic seizures alone, or predominant myoclonus combined with generalized tonic-clonic seizures (GTCS) and/or absences, in early childhood, and discuss its classification., Methods: Forty-two children were retrospectively recruited between January 2006 and June 2015., Results: The mean age of seizure onset was 40.5months. They were divided into 4 groups: myoclonic seizures alone; predominant myoclonus combined with GTCS; predominant myoclonus combined with absences; predominant myoclonus combined with both GTCS and absences. Interictal EEG showed generalized spike- or polyspike-wave discharges at 2-4Hz. Seizures were controlled in 22 patients at a mean age of 60.5months. The psychomotor development was normal (30/37) or mildly delayed (7/37)., Conclusions: We reported a cohort of patients with early childhood myoclonic epilepsy (ECME), with the following characteristics: Seizures started below 5years old in otherwise normal children; Seizure types included myoclonic seizures alone or combined with GTCS and/or absences; Febrile or afebrile GTCS might appear firstly; Interictal EEG showed generalized spike- or polyspike-wave; Seizures usually were in remission before adolescence with normal development or mild cognitive or behavioral deficits in most., Significance: ECME might be an independent epileptic syndrome not established by International League Against Epilepsy (ILAE) previously., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Recent studies have shown a possible coexistence of absence seizures with other forms of epilepsy. The purpose of this study was to ascertain the possible contemporary or subsequent presence of childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS) in pediatric epileptic patients., Data Sources: A PubMed systematic search indexed for MEDLINE, PubMed and EMBASE was undertaken to identify studies in children including articles written between 1996 and 2015. Retrospective studies, meta-analysis and case reports were included. The list of references of all the relevant articles was also studied. The date of our last search was December 2015., Results: Review of the literature revealed 19 cases, 8 females and 11 males, reporting a consecutive or contemporary coexistence of CAE and BECTS within the same patients. Patient's age ranged between 4 and 12 years. Three out of 19 patients presented concomitant features of both syndromes, whereas 16 patients experienced the two syndromes at different times., Conclusions: BECTS and CAE may be pathophysiologically related, and the two epileptic phenotypes may indicate a neurobiological continuum. Further studies are needed to elucidate a probable genetic or functional link between partial and primarily generalized electro-clinical patterns in idiopathic childhood epilepsies.

Background: High frequency oscillations (HFOs) have provided a new insight in understanding ictogenesis and seizure localization. In absence seizures, HFOs were predominantly localized in the medial prefrontal cortex (MPFC) in MEG studies., Methods: We studied HFOs (80-250 Hz) in scalp EEGs in patients with absence epilepsy, and evaluated their frequency bandwidth and spatial-temporal distribution. EEG of 9 patients with absence epilepsy (CAE:JAE-8:1; M:F=7:2; age: 8.1 ± 2.1 years; age at onset: 6.6 ± 1.3 years) were evaluated with scalp EEG (sampling rate: 2048 Hz). Finite impulse response filters on the unipolar or longitudinal bipolar montages were band-passed between 80 and 250 Hz using Cartool(®) and EEGLAB(®). Sensitivity and paper speed were modified accordingly to study the HFOs. Thousand four hundred and thirty eight artifact free 'spike-wave' epileptiform discharges were analyzed. Sleep ictal SW discharges, defined as runs of 3 Hz GSWDs lasting ≥ 4s in stages 1 and 2 sleep, were analyzed by independent component analysis and component time-frequency and channel time-frequency maps using cyclical tapering wavelet transform. A total of 926 HFOs were identified of 1438 GSWDS., Results: The HFOs were associated with inter-ictal generalized spike-wave discharges (IiGSWDs-241/454), ictal GSWDs (IcGSWD-634/884), sporadic SWDs (sSWDs-51/100). The percentage of HFOs was higher in IcGSWD when compared to both IiGSWDs and sporadic SWDs together (χ(2)=52.864, d.o.f=1, p<0.0001). The mean frequency of HFOs was 96.4 ± 10.4 Hz. A channel wise analysis showed the maximum HFO band width in the right fronto-central region (F4=28 Hz, C4=24 Hz)., Conclusion: Narrow bandwidth interictal and ictal HFOs can be identified in scalp EEG of patients with absence epilepsy. Further characterization of the various properties of pHFOs will be helpful in opening up a domain of clinical evaluation and interpretation of the various epileptic disorders. To improve the insights into the onset and spread of absence seizures, and to study the network properties, one could analyze the HFOs in high density EEG arrays with multimodal integration using MEG or fMRI., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Hyperventilation induces absence seizures in children with absence epilepsy, and routine electroencephalography studies include three minutes of hyperventilation. We studied the duration of hyperventilation required to provoke a first absence seizure to determine whether three minutes of the procedure are indeed necessary., Methods: Electroencephalography records of children who experienced absence seizures during hyperventilation were reviewed. The time from hyperventilation onset to a first and further seizure(s) was measured, and the occurrence of absences during the posthyperventilation phase was also noted., Results: Sixty-two studies were evaluated. Mean time from hyperventilation onset to a first absence was 52 seconds (median 32 seconds). The vast majority (85.5%) had an absence within 90 seconds. Most (68%) children sustained a single event. All eight children with posthyperventilation seizures had experienced at least one event during hyperventilation., Conclusions: Our findings suggest that current guidelines for routine pediatric electroencephalography recording requiring three minutes of hyperventilation may not be clinically necessary. We found that the vast majority of children referred for suspected absence seizures experience a seizure less than 90 seconds after hyperventilation onset, and even more so by 120 seconds. Hence, a larger prospective study is warranted to establish more accurate hyperventilation duration parameters. We also suggest that once an absence seizure has been recorded at any time during hyperventilation, this procedure could be stopped, thus reducing the amount of discomfort for the child., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Correct diagnosis of seizure type and epilepsy syndrome is the foundation for appropriate antiepileptic drug selection. Inappropriate medication choices occur in the treatment of generalized epilepsy and may aggravate some seizure types, including absence seizures, potentially leading to pseudo-drug resistance. Fortunately, a correct diagnosis of absence seizures is usually not difficult, though rarely demonstrates electroclinical overlap with focal seizures. EEG can be especially misleading when secondary bilateral synchronous discharges occur in patients with focal seizures. However, the semiology of focal seizures associated with mesial temporal lobe epilepsy has a characteristic and consistent semiology that is the mark of this common epilepsy syndrome in adulthood. We recently encountered a 53-year-old female with refractory seizures and a semiology strongly suggesting mesial temporal lobe epilepsy. Instead of focal seizures, prolonged absence seizures were validated by video-EEG monitoring and she became seizure-free after a change to broad-spectrum antiepileptic drugs. This case further expands our understanding of the complexity of semiology in electroclinical classification and the spectrum that may occur in adult absence seizures. It serves to underscore the need for ictal EEG recordings and the importance of concordance with the clinical course during the pre-surgical evaluation of patients with lesions and drug-resistant epilepsy. [Published with video sequences].

Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. Genetic absence epilepsy rats of Strasbourg (GAERS) and Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence, but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies using the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2- to 3-month-old naive female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest, which continued for months. Males exhibited SWDs only after 3 months of age, consistent with previous reports (Buzsáki et al., 1990). Housing in atypical lighting during early life appeared to facilitate the incidence of SWDs. Spike-wave discharges were often accompanied by behaviors similar to stage 1-2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to that of hippocampal theta rhythm during exploration for a given animal, typically 7-8 Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250 Hz) during SWDs, suggesting that neuronal activity in the hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal, and cortical neurons do not prevent SWDs, at least in this animal model. The results suggest that it is possible that SWDs occur in rodent models of TLE and that investigators mistakenly assume that they are stage 1-2 limbic seizures. We discuss the implications of the results and ways to avoid the potential problems associated with SWDs in animal models of TLE., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Typical absence seizures (TAS) are seen in idiopathic generalized epilepsy. Electroencephalography (EEG) contributes to syndrome characterization and counseling in an area where genetics does not currently play a significant role. Prominent interictal EEG findings are seen in juvenile absence epilepsy (JAE) and are thus thought to be associated with less favorable outcome in any TAS case despite lack of evidence. Our study evaluates EEG findings and their association with seizure outcomes in children with TAS. Retrospective cohort study of 123 children over 10 years with extensive EEG analysis and medical record review. Phone interviews ascertained longer-term outcomes. EEG reviewers were unaware of outcomes. Total cohort included 123 children with phone review completed in 98. Median follow-up was 5 years 9 months. Seizure freedom was seen in 59% off antiseizure medicines (ASMs). Interictal findings included focal discharges in 29%, fragments of spike-wave (SW) discharges in 82.1%, and generalized interictal discharges in 63.4%. Interictal SW was more likely in those who slept (100%, 18 of 18) versus those who did not (57%, 60 of 105) (P < 0.001). Outcome analysis found no associations between focal or generalized interictal findings and seizure freedom, relapse off ASM, occurrence of other seizure types, or response to first ASM. Focal and generalized interictal EEG discharges are common in children with TAS and are not associated with poorer outcomes. These interictal findings were traditionally associated with JAE rather than childhood absence epilepsy and were thus believed to be associated with potentially poorer outcome, which is probably not the case. [ABSTRACT FROM AUTHOR]

To analyze the ictal and interictal electroencephalographic (EEG) features in newly diagnosed childhood absence epilepsy (CAE) and determine the association between seizure onset topography, interictal focal spike-wave discharges (FSWDs) and accompanying clinical features of absence seizures. The authors searched the EEG database for a definite diagnosis of CAE according to ILAE 2017 criteria. Video-EEGs of untreated pediatric patients during sleep and wakefulness were evaluated retrospectively. The study included 47 patients (25 males, 22 females). Interictal FSWDs were observed in 49% of patients with CAE during wakefulness and in 85.1% during sleep (p = 0.001). Interictal FSWDs were most frequently observed in the frontal regions (awake: 34%; asleep: 74.5%), followed by the posterior temporoparietooccipital region (awake: 21.2%; asleep: 36.1%), and the centrotemporal region (awake: 6.4%; asleep: 8.5%). Eleven patients (23.4%) had polyspikes during sleep. Both bilateral symmetric and asymmetric seizure onset were noted in 32%, whereas focal seizure onset was observed in 14.9% of the patients. Absence seizures with and without motor components were seen in 72.3% and 61.7% of patients, respectively, and in 33% of patients both occurred. There were no associations between the existence of interictal FSWDs, focal/asymmetric seizure onset, and absence seizures with and/or without motor components. Asymmetric and/or focal seizure onset, interictal FSWDs, and absence seizures with motor components are commonly observed in drug-naive CAE. This study found no association between seizure onset topography, interictal FSWDs, and semiological features of absence seizures. [ABSTRACT FROM AUTHOR]

Purpose: This study was to deepen into the electro-clinical relationship and source analysis of absence seizures in childhood. Methods: Thirty-three subjects were studied with clinical and electrophysiological diagnosis of absence seizures without antiepileptic medication, video-electroencephalogram was applied. We obtained clinical behavior and electrophysiological variables during seizures and General Linear Model was applied, with p < 0.05. Source analysis was carried out with VARETA method. Results: 174 seizures were evaluated. 75.75% showed interictal epileptiform discharges (IED) and 12.12% showed posterior delta activity. There was an unequal behavior in relation with total electro-clinical seizures and presence or no of IED (p = 0.02), namely between subjects without IED in EEG and multifocal EEG (p = 0.008). Quantity of seizures recorded during HPV had a different behavior between subjects without IED in EEG and multifocal EEG (p = 0.03) and between focal and multifocal EEG (p = 0.04). Source analysis (VARETA) evidence the onset frontal of seizures in 57.47%, mesial and dorsolateral regions in 43% and 57%, respectively. Conclusion: These data suggest that absence seizures are not "generalized" if we considered global cortical activation but rather involve localized discharges from specific cortical regions, mainly frontal lobe. [ABSTRACT FROM AUTHOR]

The purpose of this review is to provide a comprehensive update and highlight the distinct electroclinical features and discuss recent advances in the etiology, pathophysiology, and management strategies of epilepsy with eyelid myoclonia. Recent studies indicate that variations of certain genes including CHD2 (chromodomain helicase DNA-binding protein 2), KCNB1, KIAA2022, and NAA10 may occur in these patients. It has been postulated that the occipital cortex may play a role in the pathophysiology. Recent studies of functional imaging and connectivity of neuronal electrical activity have provided additional evidence to support this hypothesis. The frontal cortex has additionally been implicated, and it has been suggested that the epileptic cortex may extend beyond the occipital cortex to involve the posterior temporal cortex. We update the management strategies and describe tools that may predict seizure persistence. Epilepsy with eyelid myoclonias, or Jeavons syndrome, is an idiopathic generalized epilepsy characterized by the triad of eyelid myoclonia with or without absence seizures, eyelid closure-elicited electroencephalographic (EEG) paroxysms (epileptiform discharges and/or seizures), and photosensitivity. This condition may account for up to 13% of generalized epilepsies. However, it is frequently under-reported and under-recognized. Many of the patients develop medically refractory epilepsy, and seizures tend to persist throughout life. [ABSTRACT FROM AUTHOR]

Advances in electroencephalography (EEG) equipment now allow monitoring of people with epilepsy in their daily-life environment. The large volumes of data that can be collected from long-term out-of-clinic monitoring require novel algorithms to process the recordings on board of the device to identify and log or transmit only relevant data epochs. Existing seizure-detection algorithms are generally designed for post-processing purposes, so that memory and computing power are rarely considered as constraints. We propose a novel multi-channel EEG signal processing method for automated absence seizure detection which is specifically designed to run on a microcontroller with minimal memory and processing power. It is based on a linear multi-channel filter that is precomputed offline in a data-driven fashion based on the spatial-temporal signature of the seizure and peak interference statistics. At run-time, the algorithm requires only standard linear filtering operations, which are cheap and efficient to compute, in particular on microcontrollers with a multiply-accumulate unit (MAC). For validation, a dataset of eight patients with juvenile absence epilepsy was collected. Patients were equipped with a 20-channel mobile EEG unit and discharged for a day-long recording. The algorithm achieves a median of 0.5 false detections per day at 95% sensitivity. We compare our algorithm with state-of-the-art absence seizure detection algorithms and conclude it performs on par with these at a much lower computational cost. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) can play a crucial role in themodulation of absence seizures, yet relevant biophysical mechanisms are not completely established. In this paper, on the basis of a biophysical mean-field model, we investigate a typical absence epilepsy activity by introducing slow kinetics of GABAB receptors on thalamus reticular nucleus (TRN).We find that the region of spike and slow-wave discharges (SWDs) can be reduced greatly when we add the DBS to TRN. Furthermore, we systematically explore how the corresponding stimulation parameters including frequency, amplitude and positive input duration suppress the SWDs under certain conditions. It is shown that the SWDs can be controlled as key stimulation parameters are suitably chosen. The results in this paper can be helpful for researchers to understand the thalamus stimulation in treating epilepsy patients, and provide theoretical basis for future experimental and clinical studies. [ABSTRACT FROM AUTHOR]

The Solute Carrier Family 6 Member 1 (SLC6A1) gene encodes the gamma-aminobutyric acid (GABA) transporter 1, which is one of the main GABA transporters. The clinical picture of SLC6A1 gene mutations is characterized by a broader spectrum including a mild-to-moderate intellectual disability, speech difficulties, behavioral problems, epilepsy (often with myoclonic-atonic and atypical absence seizures, characterizing a myoclonic-atonic epilepsy), and neurological signs. We describe a boy with an SLC6A1 mutation and a milder phenotype, characterized by a learning disorder without intellectual disability, nonspecific dysmorphisms, and an electroencephalogram picture closely resembling that of myoclonic-atonic epilepsy with brief absence seizures that have appeared during the follow-up, responsive to valproic acid. [ABSTRACT FROM AUTHOR]

The purpose of this article is to provide an overview of the electroclinical features and pathophysiological findings, as well as the neuropsychological characteristics of absence epilepsies. Absence seizures are primary generalized, non-convulsive seizures. The classical clinical manifestations of typical absence seizures are a transient impairment of consciousness (with abrupt onset and offset) accompanied by staring, blinking and various forms of head/limb automatism. Atypical absence attacks are characterized by a milder beginning and end of the attack, more expressed changes in muscular tone, less severe disorders of consciousness, and longer duration compared to typical attacks. EEG findings in absence epilepsies have a characteristic pattern, demonstrating generalized spike and wave complexes that are typically 2.5-4 Hz. Treatment depends on the type of epilepsy, but usually includes valproic acid and ethosuximide. Because of their benign nature and lack of clinical presentation that resembles "real" epilepsy, absence attacks are often interpreted as daydreaming or simply a lack of attention, and therefore often the first signs of the disease are often not recognized. Conclusion: A better understanding of absence epilepsies is very important in order to develop strategies that will improve these children's quality of life. [ABSTRACT FROM AUTHOR]

Synchrony in the brain functioning describes the mode that the components are interacted and reflect the collective behaviour of neuronal assemblies. Nevertheless, the excessive and prolonged coupling among brain sites is relevant with disturbed information routing. In the present study we investigated the possibility that the sustained oscillatory states and the common mode in which several brain sites vary their functional connectivity inhibit the ability of the brain in perceiving and processing information. The hypothesis, that in many interacting systems, greater regularity–rhythmicity corresponds to grater component self-organization and isolation, is investigated in the case of thought blocks (under persistent auditory verbal hallucinations) and epileptic absences (under spike wave discharges). Our findings indicate that the observed common mode of coupling significantly restrains the normal flow of mental processes. This erroneous “connectivity mode” in the presence of symptoms such as thought blocks and absences respectively, was found to eliminate the spontaneous synchrony variability, essentially needed for the information processing, by fixating the functional specificity of the respected brain sites. [ABSTRACT FROM AUTHOR]

Permutation entropy (PE) has been widely exploited to measure the complexity of the electroencephalogram (EEG), especially when complexity is linked to diagnostic information embedded in the EEG. Recently, the authors proposed a spatial-temporal analysis of the EEG recordings of absence epilepsy patients based on PE. The goal here is to improve the ability of PE in discriminating interictal states from ictal states in absence seizure EEG. For this purpose, a parametrical definition of permutation entropy is introduced here in the field of epileptic EEG analysis: the permutation Rényi entropy (PEr). PEr has been extensively tested against PE by tuning the involved parameters (order, delay time and alpha). The achieved results demonstrate that PEr outperforms PE, as there is a statistically-significant, wider gap between the PEr levels during the interictal states and PEr levels observed in the ictal states compared to PE. PEr also outperformed PE as the input to a classifier aimed at discriminating interictal from ictal states. [ABSTRACT FROM AUTHOR]

Absence seizures are transient episodes of impaired consciousness accompanied by 3–4 Hz spike–wave discharge on electroencephalography (EEG). Human functional magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (BOLD) signal that may play an important role in the pathophysiology of these seizures. Animal models could provide an opportunity to investigate the fundamental mechanisms of these changes, however they have so far failed to consistently replicate the cortical fMRI decreases observed in human patients. This may be due to important differences between human seizures and animal models, including a lack of cortical development in rodents or differences in the frequencies of rodent (7–8 Hz) and human (3–4 Hz) spike–wave discharges. To examine the possible contributions of these differences, we developed a ferret model that exhibits 3–4 Hz spike–wave seizures in the presence of a sulcated cortex. Measurements of BOLD fMRI and simultaneous EEG demonstrated cortical fMRI increases during and following spike–wave seizures in ferrets. However unlike human patients, significant fMRI decreases were not observed. The lack of fMRI decreases was consistent across seizures of different durations, discharge frequencies, and anesthetic regimes, and using fMRI analysis models similar to human patients. In contrast, generalized tonic–clonic seizures under the same conditions elicited sustained postictal fMRI decreases, verifying that the lack of fMRI decreases with spike–wave was not due to technical factors. These findings demonstrate that 3–4 Hz spike–wave discharge in a sulcated animal model does not necessarily produce fMRI decreases, leaving the mechanism for this phenomenon open for further investigation. [ABSTRACT FROM AUTHOR]

Objective Originally derived from a Wistar rat strain, a proportion of which displayed spontaneous absence-type seizures, Genetic Absence Epilepsy Rats from Strasbourg ( GAERS) represent the most widely utilized animal model of genetic generalized epilepsy. Here we compare the seizure, behavioral, and brain morphometric characteristics of four main GAERS colonies that are being actively studied internationally: two from Melbourne ( MELB and STRAS- MELB), one from Grenoble ( GREN), and one from Istanbul ( ISTAN). Methods Electroencephalography (EEG) recordings, behavioral examinations, and structural magnetic resonance imaging (MRI) studies were conducted on GAERS and Non-Epileptic Control ( NEC) rats to assess and compare the following: (1) characteristics of spike-and-wave discharges, (2) anxiety-like and depressive-like behaviors, and (3) MRI brain morphology of regions of interest. Results Seizure characteristics varied between the colonies, with MELB GAERS exhibiting the least severe epilepsy phenotype with respect to seizure frequency, and GREN GAERS exhibiting four times more seizures than MELB. MELB and STRAS- MELB colonies both displayed consistent anxiety and depressive-like behaviors relative to NEC. MELB and GREN GAERS showed similar changes in brain morphology, including increased whole brain volume and increased somatosensory cortical width. A previously identified mutation in the Cacna1h gene controlling the CaV3.2 T-type calcium channel (R1584P) was present in all four GAERS colonies, but absent in all NEC rats. Significance This study demonstrates differences in epilepsy severity between GAERS colonies that were derived from the same original colony in Strasbourg. This multi-institute study highlights the potential impact of environmental conditions and/or genetic drift on the severity of epileptic and behavioral phenotypes in rodent models of epilepsy. [ABSTRACT FROM AUTHOR]

We evaluated the long-term prognosis of patients featuring the association of absence s and myoclonic epilepsy of infancy. Our cohort consisted of 10 male subjects with mean age at seizure onset of 29 months. Follow-up data included seizure outcome and EEG findings. All individuals received antiepileptic drugs (AEDs) as monotherapy (6 patients) or polytherapy (4 patients) for a mean period of 24 months. Over a 30–60 month evaluation period (mean: 43 months), all patients were seizure-free. Follow-up data after withdrawal of antiepileptic therapy were obtained for a mean period of 22 months. None of the children did develop other age-related epileptic syndrome after AEDs discontinuation. Furthermore, follow-up EEG data after drugs withdrawal were normal and none of the patients showed cognitive impairment. In conclusion, we confirm that absence seizures may occur in association with myoclonic epilepsy of infancy. This condition shows excellent prognosis with either favourable neurologic development and seizure outcome in these children. [ABSTRACT FROM AUTHOR]

Absence seizures (AS) are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning, and memory.A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation, which relies heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI) is one such technique that provides an opportunity to explore the interactions between brain structures involved inAS generation.A number of fMRI techniques including event-related analysis, time-course analysis, and functional connectivity (FC) have identified a common network of structures involved in AS. This network comprises the thalamus, midline, and lateral parietal cortex [the default mode network (DMN)], caudate nuclei, and the reticular structures of the pons. The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time-course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered FC in patients with AS. Hence, it appears that engagement of this network is central to AS. In this review, we will explore the insights of EEG-fMRI studies into the mechanisms of AS and consider how the DMN is likely to be the major large-scale brain network central to both seizure generation and seizure manifestations. [ABSTRACT FROM AUTHOR]

Generalized and focal seizures can rarely be seen in galactosemia patients, but absence seizures were not reported previously. An 18-year-old male was diagnosed as galactosemia at the age of 8 months. No family history of epilepsy was present. His absence seizures realized at the age of 9 years. Generalized 3-4 Hz spike-wave discharges were identified in his electroencephalography. Homozygous mutation at exon 6 c. 563A > G was identified. The electroencephalogram of his sibling was unremarkable. Our aim was to present the long-term follow-up of a patient diagnosed with galactosemia, who had phantom absence seizures and typical 3-4 Hz spike-wave discharges in his electroencephalogram to draw attention to this rare association. [ABSTRACT FROM AUTHOR]

Abstract: Intrinsic connectivity network (ICN) technique provides a feasible way for evaluating cognitive impairments in epilepsy. This EEG–fMRI study aims to comprehensively assess the alterations of ICNs affected by generalized spike-and-wave discharge (GSWD) during absence seizure (AS). Twelve fMRI sessions with GSWD, and individually paired non-GSWD sessions were acquired from 16 patients with AS. Ten ICNs corresponding to seizure origination and cognitive processes were extracted using independent component analysis. Intra- and inter-network connectivity alterations of the ICNs were observed through comparisons between GSWD and non-GSWD sessions. Sequential correlation analysis between GSWD and the ICN time courses addressed the immediate effects of GSWD on ICNs during AS. GSWD-related increase of intra-network connectivity was found only in the thalamus, and extensive decreases were found in the ICNs corresponding to higher-order cognitive processes including the default-mode network, dorsal attention network, central executive network and salience network. The perceptive networks and motor network were less affected by GSWD. Sequential correlation analysis further demonstrated different responses of the ICNs to GSWD. In addition to GSWD-related functional excitation in the thalamus and functional suspension in the default-mode network, this study revealed extensive inhibitions in the other ICNs corresponding to higher-order cognitive processes, and spared perceptive and motor processes in AS. GSWD elevated synchronization of brain network activity and sequentially affected the ICNs. [Copyright &y& Elsevier]

Highlights: [•] Two patients were identified with absence seizures (AS). [•] Subjects had co-existent and peri-ventricular nodular heterotopia (PNH). [•] EEG fMRI was used to explore the potential association between PNH and AS. [•] The PNH displayed connectivity to the typical absence network. [•] This study demonstrates that fMRI may be used to understand complex networks. [Copyright &y& Elsevier]

Absence seizures are caused by brief periods of abnormal synchronized oscillations in the thalamocortical loops, resulting in widespread spike-and-wave discharges (SWDs) in the electroencephalogram (EEG). SWDs are concomitant with a complete or partial impairment of consciousness, notably expressed by an interruption of ongoing behaviour together with a lack of conscious perception of external stimuli. It is largely considered that the paroxysmal synchronizations during the epileptic episode transiently render the thalamocortical system incapable of transmitting primary sensory information to the cortex. Here, we examined in young patients and in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established genetic model of absence epilepsy, how sensory inputs are processed in the related cortical areas during SWDs. In epileptic patients, visual event-related potentials (ERPs) were still present in the occipital EEG when the stimuli were delivered during seizures, with a significant increase in amplitude compared to interictal periods and a decrease in latency compared to that measured from non-epileptic subjects. Using simultaneous in vivo EEG and intracellular recordings from the primary somatosensory cortex of GAERS and non-epileptic rats, we found that ERPs and firing responses of related pyramidal neurons to whisker deflection were not significantly modified during SWDs. However, the intracellular subthreshold synaptic responses in somatosensory cortical neurons during seizures had larger amplitude compared to quiescent situations. These convergent findings from human patients and a rodent genetic model show the persistence of cortical responses to sensory stimulations during SWDs, indicating that the brain can still process external stimuli during absence seizures. They also demonstrate that the disruption of conscious perception during absences is not due to an obliteration of information transfer in the thalamocortical system. The possible mechanisms rendering the cortical operation ineffective for conscious perception are discussed, but their definite elucidation will require further investigations. [ABSTRACT FROM AUTHOR]

Summary: We studied clinical and EEG manifestations of absence seizures (AS) in children with Dravet syndrome (DS) to clarify their characteristic features and differences from those of typical AS (TAS). The subjects were 12 children with DS. We retrospectively analyzed electroclinical characteristics of AS. We analyzed a total of 102 ictal EEGs characterized by generalized spike-and-wave (GSW) and semiology of 78 video-taped AS. The mean age at the onset of AS and at the time of the study was 16.2±7.1 months and 40.3±22.1 months, respectively. Ictal EEG showed the focality of initial discharge in 49/102 (48%), a duration ranging from 2 to 180s (mean: 10.2±22.6s; median: 4.0s), frequency ranging from 2 to 4Hz (median=3.0Hz), and irregular and disorganized GSW morphology in 66/102 (65%). AS manifested with eyelid-myoclonus and generalized myoclonus in 9/54 (17%) and 34/78 (44%), respectively. In conclusion, AS in DS were characterized by an early-onset age, a high incidence of irregular and disorganized 3Hz GSW morphology, and the frequent association of generalized myoclonic movement as well as the absence of automatism as compared to TAS. The results should be appreciated in the differential diagnosis of early-onset AS, the treatment of AS in DS and also a further clinical and genetic study for DS. [Copyright &y& Elsevier]

Epileptic seizures are thought to be generated and to evolve through an underlying anomaly of synchronization in the activity of groups of neuronal populations. The related dynamic scenario of state transitions is revealed by detecting changes in the dynamical properties of Electroencephalography (EEG) signals. The recruitment procedure ending with the crisis can be explored through a spatial-temporal plot from which to extract suitable descriptors that are able to monitor and quantify the evolving synchronization level from the EEG tracings. In this paper, a spatial-temporal analysis of EEG recordings based on the concept of permutation entropy (PE) is proposed. The performance of PE are tested on a database of 24 patients affected by absence (generalized) seizures. The results achieved are compared to the dynamical behavior of the EEG of 40 healthy subjects. Being PE a feature which is dependent on two parameters, an extensive study of the sensitivity of the performance of PE with respect to the parameters' setting was carried out on scalp EEG. Once the optimal PE configuration was determined, its ability to detect the different brain states was evaluated. According to the results here presented, it seems that the widely accepted model of "jump" transition to absence seizure should be in some cases coupled (or substituted) by a gradual transition model characteristic of self-organizing networks. Indeed, it appears that the transition to the epileptic status is heralded before the preictal state, ever since the interictal stages. As a matter of fact, within the limits of the analyzed database, the frontal-temporal scalp areas appear constantly associated to PE levels higher compared to the remaining electrodes, whereas the parieto-occipital areas appear associated to lower PE values. The EEG of healthy subjects neither shows any similar dynamic behavior nor exhibits any recurrent portrait in PE topography. [ABSTRACT FROM AUTHOR]

Abstract: Although stress can alter the susceptibility of patients and animal models to convulsive epilepsy, little is known about the role of stress and glucocorticoid hormones in absence epilepsy. We measured the basal and acute stress-induced (foot-shocks: FS) concentrations of corticosterone in WAG/Rij rats, non-epileptic inbred ACI rats and outbred Wistar rats. The WAG/Rij strain is a genetic model for absence epilepsy and comorbidity for depression, which originates from the population of Wistar rats and, therefore, shares their genetic background. In a separate experiment, WAG/Rij rats were exposed to FS on three consecutive days. Electroencephalograms (EEGs) were recorded before and after FS, and the number of absence seizures (spike-wave-discharges, SWDs) was quantified. Both WAG/Rij rats and ACI rats exhibited elevated basal levels of corticosterone and a rapid corticosterone increase in response to acute stress. The WAG/Rij rats also displayed the most rapid normalization of corticosterone during the recovery phase compared to that of ACI and Wistar rats. FS had a biphasic effect on SWDs; an initial suppression was followed by an aggravation of the SWDs. By the third day, this aggravation of seizures was present in the hour preceding FS. This increase in SWDs may arise from anticipatory stress about the upcoming FS. Together, these results suggest that the distinct secretion profile of corticosterone found in WAG/Rij rats may contribute to the severity of the epileptic phenotype. Although the acute stressor results in an initial suppression of SWDs followed by an increase in SWDs, stress prior to a predictable negative event aggravates absences. [Copyright &y& Elsevier]

Abstract: Interleukin (IL)-1β plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1β signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1β biosynthesis in GAERS could affect SWD activity. IL-1β expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet, IL-1β immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1β was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1β was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS. Inhibition of IL-1β biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration. These results show that IL-1β is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1β has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures. [Copyright &y& Elsevier]

Abstract: Rodent models of absence seizures are used to investigate the network properties and regulatory mechanisms of the seizure''s generalized spike and wave discharge (SWD). As rats age, SWDs occur more frequently, suggesting aging-related changes in the regulation of the corticothalamic mechanisms generating the SWD. We hypothesized that brain resetting mechanisms – how the brain “resets” itself to a more normal functional state following a transient period of abnormal function, e.g., a SWD – are impaired in aged animals and that brain infarction would further affect these resetting mechanisms. The main objective of this study was to determine the effects of aging, infarction, and their potential interaction on the resetting of EEG dynamics assessed by quantitative EEG (qEEG) measures of linear (signal energy measured by amplitude variation; signal frequency measured by mean zero-crossings) and nonlinear (signal complexity measured by the pattern match regularity statistic and the short-term maximum Lyapunov exponent) brain EEG dynamics in 4- and 20-month-old F344 rats with and without brain infarction. The main findings of the study were: 1) dynamic resetting of both linear and nonlinear EEG characteristics occurred following SWDs; 2) animal age significantly affected the degree of dynamic resetting in all four qEEG measures: SWDs in older rats exhibited a lower degree of dynamic resetting; 3) infarction significantly affected the degree of dynamic resetting only in terms of EEG signal complexity: SWDs in infarcted rats exhibited a lower degree of dynamic resetting; and 4) in all four qEEG measures, there was no significant interaction effect between age and infarction on dynamic resetting. We conclude that recovery of the brain to its interictal state following SWDs was better in young adult animals compared with aged animals, and to a lesser degree, in age-matched controls compared with infarction-injured animal groups, suggesting possible effects of brain resetting mechanisms and/or the disruption of the epileptogenic network that triggers SWDs. [Copyright &y& Elsevier]

Abstract: Objective: To determine the effect of withdrawal of ovarian hormones on the occurrence of absence seizures in WAG/Rij rats, a well-validated animal model for absence epilepsy. Methods: Two weeks after electroencephalography (EEG) electrodes were implanted, video-EEG recordings of 16 adult female WAG/Rij rats were made. The rats were then randomly assigned to undergo ovariectomy or sham surgery. One week after surgical procedures, EEG recordings were made for five consecutive days. The EEGs were amplified and filtered between 1 and 100Hz and digitized at 200Hz. Results: In the ovariectomy group, both duration and the number of spike-wave discharges increased. Conclusion: The present data suggest that ovariectomy enhances the occurrence of spike-wave discharges and absence seizures in WAG/Rij rats. [Copyright &y& Elsevier]

To evaluate the potential efficacy of levetiracetam as an antiabsence agent in children and adolescents with newly diagnosed childhood or juvenile absence epilepsy. Patients were randomized in a 2:1 ratio to receive de novo monotherapy with levetiracetam (up to 30 mg/kg/day) or placebo for 2 weeks under double-blind conditions. Responder status (primary end point) was defined as freedom from clinical seizures on days 13 and 14 and from electroencephalographic (EEG) seizures during a standard EEG recording with hyperventilation and intermittent photic stimulation on day 14. The double-blind phase was followed by an open-label follow-up. Nine of 38 patients (23.7%) were responders in the levetiracetam group, compared with one of 21 (4.8%) in the placebo group (p = 0.08). Seven of 38 patients (18.4%) were free from clinical and EEG seizures during the last 4 days of the trial (including 24-h EEG monitoring on day 14) compared with none of the patients treated with placebo (p = 0.04). Seventeen patients remained seizure-free on levetiracetam after 1 year follow-up. Of the 41 patients who discontinued levetiracetam due to lack of efficacy (n = 39) or adverse events (n = 2), 34 became seizure-free on other treatments. Although superiority to placebo just failed to reach statistical significance for the primary end point, the overall findings are consistent with levetiracetam having modest efficacy against absence seizures. Further controlled trials exploring larger doses and an active comparator are required to determine the role of levetiracetam in the treatment of absence epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In order to unravel the mechanisms underlying the “sudden” onset of spontaneous absences in genetically prone subjects, we investigated the immediate precursors of spike–wave discharges (SWDs) produced in cortico-thalamo-cortical neuronal networks. Methods: A time–frequency analysis of the cortical and thalamic ECoG of WAG/Rij rats was accomplished with a continuous wavelet decomposition of SWDs, 3s prior to the onset of SWDs (pre-SWD), and in control periods devoid of SWDs. Results: The pre-SWD ECoG consisted of delta and theta components in 80–90% of all SWDs simultaneously in cortex and thalamus, the co-occurrence of delta and theta was rare (7%) during control periods. The occurrence of delta and theta events in pre-SWDs in the cortex preceded that in the thalamus. The frequency of theta component in cortex correlated positively with that in thalamus, this correlation was less strong for delta. Conclusion: Precursors of SWDs comprise of delta and theta, their co-occurrence is typical for non-epileptic periods. Thalamic and cortical theta are strongly related. Rhythmic precursors appear earlier in cortex than in thalamus, and this is in line with the cortical origin of SWD. Significance: Simultaneous presence of delta and theta events in EEG is a condition for the occurrence of SWDs. [Copyright &y& Elsevier]

Early onset absence seizures have been considered a rare heterogeneous group with a poor prognosis. Only few patients may be categorized into well-known syndromes. We have evaluated electroclinical features, evolution, and the nosologic boundaries of early onset absence seizures. Forty-six neurologically normal patients with absence seizures associated with bilateral, synchronic, or asynchronic, and symmetric or asymmetric spike-and-wave paroxysms with onset in the first 3 years of life were included. Patients with abnormal neurologic examination and brain imaging were excluded from the study. In our study, 39 patients met the clinical and electroencephalography (EEG) criteria of well-defined epileptic syndromes. Childhood absence epilepsy was found in 11 patients, benign myoclonic epilepsy in infancy in 18 patients, eyelid myoclonic epilepsy in 4, and epilepsy with myoclonic absences in 6. We did not find clinical and EEG criteria of well-recognized epileptic syndromes in seven children. Nine of 11 patients with simple absence seizures became seizure free. All these patients had normal neurologic and neuropsychological evaluations. Of the 35 patients who had absence seizures associated with myoclonic seizures, 20 became seizure free. Fifteen of 35 children continue having seizures. At the last visit, 20 of these 35 patients had normal neurologic and neuropsychological evaluations, 11 presented with mild mental retardation, and 4 with severe mental retardation. Epilepsies with absence seizures of early onset are relatively uncommon. Most of the patients had well-defined epileptic syndromes with a variable evolution. The evolution depended on the epileptic syndromes. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To analyze electroclinical features of absence seizures during sleep. Principal results: 30 children with genetic generalized epilepsy had 52 paroxysms of GSW >2s during sleep. 18/52 (35%) demonstrated a clinical sign. Ictal GSW lasted an average of 6.5s. Conclusion: Motor manifestations are seen during GSW>2s in sleep. 72% likely represent true ictal motor features while the rest may be serendipitous sleep phenomenon. [ABSTRACT FROM AUTHOR]