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Objective: Epidemiological studies have reported an association between epilepsy and dementia. However, the causal relationship between epilepsy and the risk of dementia is not clear. We aimed to inspect the causal effect of epilepsy on memory loss and dementia., Methods: We analyzed summary data of epilepsy, memory loss, and dementia from the genome-wide association study (GWAS) using the two-sample Mendelian randomization (MR) method. We used the estimated odds ratio of memory loss and dementia associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: all epilepsy, focal epilepsy (including focal epilepsy with hippocampal sclerosis, lesion-negative focal epilepsy, and focal epilepsy with other lesions), and genetic generalized epilepsy (including childhood absence epilepsy, generalized tonic-clonic seizures alone, Juvenile absence epilepsy, and Juvenile myoclonic epilepsy)., Results: According to the result of MR using the inverse variance weighted method (IVW), we found that genetically predicted epilepsy did not causally increase the risk of memory loss and dementia (p > 0.05). Results of the MR-Egger and weighted median method were consistent with the IVW method., Conclusions: No evidence has been found to support the notion that epilepsy can result in memory loss and dementia. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants., 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 © 2023 Elsevier Inc. All rights reserved.)

Rationale: Phantom absences refer to mild and short-lasting absence seizures, which are usually accompanied by infrequent generalized tonic-clonic seizures and absence status. Generally, phantom absences do not impair the individual neurological functions. Herein, we report the case of a young woman with idiopathic generalized epilepsy, phantom absences, absence status, and generalized tonic-clonic seizures., Patient Concerns: A 31-year-old woman presented with a 16-year history of paroxysmal convulsions., Diagnoses: Electroencephalogram (EEG) showed recurrent universal and synchronized 3~4 Hz spike waves and spike-slow waves in the interictal phase with normal background activity. During the ictal phases, EEG revealed bursts of 3~4 Hz spike waves and spike-slow waves that were universal, synchronized, and symmetrical. Additionally, there was 1 seizure episode induced by a 3-Hz flash in the current case. Based on these findings, a diagnosis of idiopathic generalized epilepsy was made., Interventions: The patient was treated with oral sodium valproate, and the epileptic seizures were controlled., Outcomes: The frequency of absence seizures was significantly reduced and there were no generalized tonic-clonic seizures., Lessons: Idiopathic generalized epilepsy with phantom absences, absence status, and generalized tonic-clonic seizures is an extremely rare condition. EEG is the exclusive method for diagnosis. Antiepileptic drugs are effective for controlling epileptic seizures in this disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Objective: To explore the differences in sleep spindle (SS) characteristics during stage N2 sleep between children with childhood absence epilepsy and healthy controls, and between children with childhood absence epilepsy with or without cognitive impairment., Methods: We recruited 29 children (14 females, 15 males, mean age: 8 (2.5) years) with childhood absence epilepsy who did not undergone antiseizure treatments previously and 30 age-matched controls (14 females, 16 males, mean age: 9 (3.0) years). For all patients, data on medical history were collected. Each child was monitored overnight by long-term video electroencephalography and was evaluated by the Wechsler Intelligence Scale for Children-Fourth Edition. Next, we compared anterior SS characteristics, including density, frequency, cycle length, duration, amplitude, and percentage of sleep stages., Results: The childhood absence epilepsy group exhibited lower spindle density and duration in the first 37.5 min of stage N2 sleep than the control group (P < 0.01). A decrease in spindle density could be observed in the childhood absence epilepsy group with aggravated cognition impairment. The spindle density was substantially lower in the cognitively impaired group than in the cognitively unimpaired group (P < 0.01). No significant differences were observed in SS amplitude, SS frequency, SS cycle length, and the distribution of sleep stages., Conclusions: Reduction in spindle density and duration is associated with the mechanisms underlying childhood absence epilepsy. The deficit in SS density is related with impaired cognition. This deficiency in SSs may be a useful predictive indicator of cognitive impairment in children with absence epilepsy, indicating that SSs may become a useful biomarker and potential adjuvant anti-seizure target for cognitive impairment caused by childhood absence epilepsy., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: This study evaluated sleep quality, chronotype, and excessive diurnal somnolence in persons with Juvenile Myoclonic Epilepsy (JME) and their possible association with clinical variables., Methods: This cross-sectional controlled study evaluated 49 consecutive patients (65% females, mean age 27.53 years) with an electroclinical diagnosis of JME and 49 healthy controls (55% females, mean age 28.55 years). The Pittsburgh Sleep Quality Inventory (PSQI) was used to assess sleep quality and the Epworth Sleepiness Scale (ESS) to evaluate excessive daytime sleepiness. The patients' chronotype was evaluated by the Morningness-Eveningness Questionnaire (MEQ). Epilepsy-related factors gathered from the medical chart and personal interview were epilepsy duration, age at onset, frequency of myoclonic (Mcl), generalized tonic-clonic (GTC) and absence (ABS) seizures, pharmacoresponse, and current antiseizure medication (ASM)., Results: Persons with JME did not differ from the control group regarding daytime sleepiness (p=0.840); however, the JME group had worse sleep quality (p=0.01) than the controls. Persons with JME presented a more evening chronotype than controls (p = 0.003). The age at onset, epilepsy duration, frequency of Mcl seizure, frequency of GTC seizure, frequency of ABS seizure, and drug response did not predict ESS and MEQ scales. Pharmacoresponsive patients had lower PSQI scores compared with pharmacoresistant patients (p=0.036)., Conclusion: Persons with JME have worse sleep quality and a more evening chronotype. Notably, pharmacoresistant patients present a worse sleep quality that deserves attention and special care due to the relationship between sleep deprivation and seizure worsening., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Xq25 microduplication involving exclusively STAG2 is a new distinctive cohesinopathy including mild to moderate intellectual disability, speech delay and facial dysmorphism. Seizures seem to be scarce, but detailed seizure type descriptions are missing. We report the case of an 8-year-old boy with mild intellectual disability and eyelid myoclonia with onset at age of 3 years, initially misinterpreted as tics. An ictal VIDEO-EEG documented eye closure elicited generalized 3 Hz spike-waves or polyspike-waves concomitant to eyelid myoclonia, sometimes associated to brief clinically observable absences. Intermittent photic stimulation revealed a photoparoxysmal response. Array CGH identified a 199 kb copy number gain in Xq25 including the whole STAG2 gene, inherited from his asymptomatic mother. To the best of our knowledge, this is the first case of STAG2 encephalopathy fulfilling all electroclinical criteria for epilepsy with eyelid myoclonia and absences (EMA), formally named Jeavons syndrome (JS). As for other Genetic Generalized Epilepsy syndromes, EMA/JS usually occurs in normally developing children. Intellectual disability of variable degree is occasionally reported. On the background of other genes responsible for Developmental and Epileptic Encephalopathies, linked to specific generalized seizure types or seizure combinations, we discuss the contribution of pathogenic variants in CHD2, SYNGAP1 and some other genes as, RORB, NEXMIF and KCNB1 to this peculiar EMA phenotype., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

N-acetylcysteine (NAC) is an antioxidant with some demonstrated efficacy in a range of neuropsychiatric disorders. NAC has shown anticonvulsant effects in animal models. NAC effects on absence seizures are still not uncovered, and considering its clinical use as a mucolytic in patients with lung diseases, people with epilepsy are also likely to be exposed to the drug. Therefore, we aimed to study the effects of NAC on absence seizures in the WAG/Rij rat model of absence epilepsy with neuropsychiatric comorbidities. The effects of NAC chronic treatment in WAG/Rij rats were evaluated on: absence seizures at 15 and 30 days by EEG recordings and animal behaviour at 30 days on neuropsychiatric comorbidities. Furthermore, the mechanism of action of NAC was evaluated by analysing brain expression levels of some possible key targets: the excitatory amino acid transporter 2, cystine-glutamate antiporter, metabotropic glutamate receptor 2, the mechanistic target of rapamycin and p70S6K as well as levels of total glutathione. Our results demonstrate that in WAG/Rij rats, NAC treatment significantly increased the number and duration of SWDs, aggravating absence epilepsy while ameliorating neuropsychiatric comorbidities. NAC treatment was linked to an increase in brain mGlu2 receptor expression with this being likely responsible for the observed absence seizure-promoting effects. In conclusion, while confirming the positive effects on animal behaviour induced by NAC also in epileptic animals, we report the aggravating effects of NAC on absence seizures which could have some serious consequences for epilepsy patients with the possible wider use of NAC in clinical therapeutics., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Eyelid myoclonia with absences (EMA) is an epileptic syndrome characterised by eyelid myoclonia with or without absences, eye closure-induced paroxysms, and photosensitivity. The relationship between EMA and epileptic negative myoclonus has not previously been reported. Herein, we describe a case of a 10-year-old girl who presented with eyelid myoclonia, eye closure-induced paroxysms, and photosensitivity, which was compatible with the diagnosis of EMA. Ictal EEG depicted an eye closure-induced diffuse 3.0-4.5-Hz polyspike-and-wave complex, which was accompanied by eye fluttering (eyelid myoclonia). EMG disclosed a brief interruption (60-140 mseconds) of tonic contraction of the orbicularis oculi muscle, which was associated with the polyspike-and-wave complex on EEG. The findings led to the diagnosis of epileptic negative myoclonus. Eye closure-induced eyelid epileptic negative myoclonus, demonstrated in this patient, may be an atypical seizure type of EMA that represents an intermediate between eyelid myoclonia and epileptic negative myoclonus.

Pro-inflammatory cytokines have been shown to be associated with the development of seizures in the WAG/Rij rat model of absence epilepsy. Importantly, WAG/Rij rats also exhibit cognitive deficits and depression-like behaviors. It is possible that pro-inflammatory cytokines mediate these comorbid conditions of absence epilepsy given their well-established effects on cognition and affective responses. The current study investigated the potential therapeutic effect of etanercept (tumor necrosis factor inhibitor) on cognitive impairment, depression-like behavior, and spike-wave discharges (SWDs) typically observed in the WAG/Rij rats. Eight-month-old male WAG/Rij rats and Wistar controls were tested in Morris water maze (MWM), passive avoidance (PA), forced swimming, sucrose preference, and locomotor activity tests, and electroencephalogram (EEG) recordings were taken from a separate group of WAG/Rij rats after 8 weeks of etanercept or vehicle treatment. Consistent with earlier work, WAG/Rij rats exhibited cognitive deficits and depression-like behavior. From these, the cognitive deficits and despair-like behavior were rescued by etanercept administration, which also reduced the frequency of SWDs without affecting their duration. Our results support the hypothesis that pro-inflammatory cytokines mediate the absence seizures and comorbid symptoms of absence epilepsy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cognition in absence epilepsy (AE) is generally considered undisturbed. However, reports on cognitive deficits in AE in recent years have suggested otherwise. This review systematically assesses current literature on cognitive performance in children with AE. A systematic literature search was performed in Pubmed, Embase, Cochrane and Web of Science. All studies reporting on cognitive performance in children with AE were considered. In total 33 studies were eligible for inclusion. Neuropsychological tests were classified into the following domains: intelligence; executive function; attention; language; motor & sensory-perceptual examinations; visuoperceptual/visuospatial/visuoconstructional function; memory and learning; achievement. Random-effect meta-analyses were conducted by estimating the pooled mean and/or pooling the mean difference in case-control studies. Full-scale IQ in children with AE was estimated at 96.78 (95%CI:94.46-99.10) across all available studies and in case-control studies IQ was on average 8.03 (95%CI:-10.45- -5.61) lower. Verbal IQ was estimated at 97.98 (95%CI:95.80-100.16) for all studies and 9.01 (95%CI:12.11- -5.90) points lower in case-control studies. Performance IQ was estimated at 97.23 (93.24-101.22) for all available studies and 5.32 (95%CI:-8.27-2.36) points lower in case-control studies. Lower performance was most often reported in executive function (cognitive flexibility, planning, and verbal fluency) and attention (sustained, selective and divided attention). Reports on school difficulties, neurodevelopmental problems, and attentional problems were high. In conclusion, in contrast to common beliefs, lower than average neurocognitive performance was noted in multiple cognitive domains, which may influence academic and psychosocial development.

Objective: Eyelid myoclonia with absences (EMA) is a syndrome characterized by eyelid myoclonia with or without absences, eye closure-induced generalized electroencephalographic (EEG) paroxysms and photosensitivity. Few data are available about the prognostic factors of this syndrome. The main objectives of our study were to describe the clinical and EEG features of a group of patients with EMA and to evaluate the presence of prognostic factors., Methods: We retrospectively selected a cohort of patients with diagnosis of EMA evaluated in the epilepsy service of the Neurological Clinic of Catania, in the Neurology and Clinical Neurophysiopathology Unit of Oasi Research Institute, Troina and in the Regional Epilepsy Centre of Bianchi-Melacrino-Morelli Hospital of Reggio Calabria. We considered the features of the patients during the first year of disease, and at the last follow-up visit. We stratified the patients into two groups: "seizure-free", defined as the absence of seizures for at least 2 years, and "not seizure-free" and we evaluated the evolution of their characteristics and the presence of factors associated with outcome., Results: We enrolled 51 patients (40 women (78%); mean age: 30.8 years ± 15.5 [range 10-79]). The mean follow-up time was 8.7 ± 5.8 years. Eleven patients (21.6%) achieved the condition of seizure-free. Family history of epilepsy was associated with the condition of seizure-free (P = 0.05). At the last follow-up visit, EEG photosensitivity and eye closure sensitivity were significantly associated with the condition of "not seizure-free"., Significance: The results of our study revealed that a positive family history of epilepsy might be associated with a better outcome in EMA. Furthermore, the persistence of photosensitivity and eye closure sensitivity might indicate persistence of seizures, offering an aid in therapeutic management., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

The main aim of this study was to examine the cognitive profile and academic achievement of children with absence epilepsy. It is investigated whether all scale intelligence score, intelligence subscale scores, and academic achievement of the children with absence epilepsy differed from healthy peers and Turkish norm values. Nineteen children with absence epilepsy and 19 healthy children participate in the study. The Wechsler Intelligence Scale for Children-IV (WISC-IV) is used to measure their intelligence scores. A teacher assessment form (Teacher's Report Form (TRF)) is obtained from the participants' teachers for the measurement of academic achievement, and the students' report cards are collected as an additional measure of it. Participants with absence epilepsy have significantly lower scores of total intelligence score (Mean (M) = 76.68, Standard Deviation (SD) = 25.18), verbal comprehension score (M = 81.68, SD = 25.29), perceptual reasoning score (M = 85.47, SD = 20.61), processing speed score (M = 77.95, SD = 18.61), and working memory (M = 83.74, SD = 19.04), which are measured by WISC-IV, than healthy peers (respectively M = 105.84, SD = 16.20; M = 105.47, SD = 18.12; M = 103.63, SD = 12.88; M = 104.05, SD = 12.98; M = 104.74, SD = 18.97) and norm values (M = 100, SD = 10). No difference is observed between the subscale scores of WISC-IV for within group with absence epilepsy. Moreover, they have lower Turkish language (M = 73.65, SD = 19.19) and mathematics (M = 76.26, SD = 22.29) grade report scores than healthy peers (respectively M = 90.76, SD = 12.01; M = 88.64, SD = 15.93). There is no difference between the two groups in terms of the academic achievement obtained from the TRF. It is necessary to support children with absence epilepsy academically. We analyzed whether the current pattern has changed by comparing the intelligent scores and academic achievement of children with absence epilepsy who have recovered after treatment with their healthy peers. In fact, there is no difference between the children with absence epilepsy who have recovered after treatment and their healthy peers in terms of total intelligence score and its subscale scores. Similarly, there is no difference between them in terms of mathematics score on their report. Only the difference in the score of Turkish language continues in the same direction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Animal studies currently represent the best source of information also in the field of epileptogenesis research. Many animal models have been proposed and studied so far both from the pathophysiological and pharmacological point of view. Furthermore, they are widely used for the identification of potentially clinically valuable biomarkers. The WAG/Rij rat model, similarly to other genetic animal strains, represents a suitable animal model of absence epileptogenesis accompanied by depressive-like and cognitive comorbidities. Generally, animal models of epileptogenesis are characterized by an identifiable initial insult (e.g. traumatic brain injury), a latent phase lasting up to the appearance of the first spontaneous seizure and a chronic phase characterized by recurrent spontaneous seizures. In most of genetic models: the initial insult should be defined as the mutation causing epilepsy, which is not clearly defined in the WAG/Rij rat model; the latent phase ends at the appearance of the first spontaneous seizure, which is about 2-3 months of age in WAG/Rij rats and thereafter the chronic phase. WAG/Rij rats also display depressive-like comorbidity around the age of 4 months, which is apparently linked to the development of absence seizures considering both its ontogeny and the fact that drugs affecting absence seizures development also block the development of depressive-like behavior. Finally, WAG/Rij rats also display cognitive impairment in some memory tasks, however, this has not been yet definitively linked to absence seizures development and may represent an epiphenomenon. This review is focused on the effects of pharmacological treatments against epileptogenesis and their effects on comorbidities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Children with Childhood Absence Epilepsy (CAE) may develop generalized tonic-clonic seizure or juvenile myoclonic epilepsy. A possible evolution to Eyelid Myoclonia with Absence Epilepsy (EMA) hasn't been documented yet. We report the electroclinical features of a case series of children with CAE that evolved to EMA after therapy withdrawal., Method: Of 108 patients with CAE referred at our Epilepsy Center in the last ten years, 5 satisfied the inclusion criteria: CAE diagnosis, a minimum of 3 years follow-up, a progression to EMA after therapy withdrawal., Results: All the six subjects were females. CAE was characterized by typical absences induced by hyperventilation; intermittent photic stimulation (IPS) was negative. All subjects were treated successfully with valproate. After drug withdrawal, all the six girls presented EMA. EMA was characterized by eyelid myoclonia with or without brief absences related to generalized spike/polyspike-waves discharges induced by IPS and less frequently by eye-closure., Conclusions: Our study documented another possible evolution of CAE into EMA. These results support the hypothesis that these two epileptic conditions are dynamic processes evolving into one another. CAE and EMA could be considered "system epilepsy" characterized by a high susceptibility to changes in the brain networks during specific life periods such as childhood and puberty., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Photosensitivity, which is a main feature of Jeavons syndrome, can be seen in other types of idiopathic or genetic epilepsies with focal or generalized seizures and tends to disappear spontaneously usually in the second decade. Although it responds well to antiepileptic treatment, especially to valproic acid, it may continue into adulthood in rare cases., Case Report: We describe a 63-year-old male patient with eyelid myoclonia with absences, generalized tonic-clonic seizures, and severe photosensitivity accompanied by eyelid myoclonia. Seizures were treated with antiepileptic treatment, whereas photosensitivity still continued on electroencephalogram without clinical findings., Conclusion: Our elderly patient with Jeavons syndrome with ongoing remarkable photosensitivity demonstrated that it may continue to older ages, although it is uncommon.

Objective: This study aimed to compare the attention profiles of subjects with childhood absence epilepsy (CAE) to those of children with attention-deficit/hyperactivity disorder (ADHD) and controls., Method: We retrospectively reviewed the medical records of 20 children (age 7.2 ± 1.6 years, 5 boys) in whom CAE was diagnosed at the Department of Pediatric Neurology of Asan Medical Center, Seoul, Korea. ADHD and control subjects were selected from children who visited the Department of Pediatric Psychiatry and were confirmed as having or not having ADHD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). The 20 children with CAE, 20 with ADHD and 20 controls completed the Advanced Test of Attention (ATA), which is a computerized continuous performance task., Results: The CAE subjects without ADHD showed increased Omission errors (p=.013) on the visual ATA and Response time (p=0.044) on the auditory ATA than the controls, although these differences did not remain significant after multiple comparison correction. The CAE subjects without ADHD had significantly decreased Response time variability on the visual ATA than the ADHD group (p<0.001). The CAE subjects with comorbid ADHD showed increased Commission errors (p=0.020) and Response time variability (p=0.016) on the visual ATA and increased Commission errors (p=0.022) on the auditory ATA than the CAE subjects without ADHD, although statistical significance disappeared after multiple comparison adjustments., Conclusion: These findings suggest that selective attention is impaired in children with CAE and comorbid ADHD contributes to further impairment of sustained attention and response inhibition., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE)., Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week 16-20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure., Results: A total of 382 participants at baseline, 310 participants at the week 16-20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8% (95% confidence interval [CI] 6%-11%) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16-20, participants taking valproic acid had significantly higher total problems (51.7 [98.3% CI 48.6-54.7]), externalizing problems (51.4 [98.3% CI 48.5-54.3]), attention problems (57.8 [98.3% CI 55.6-60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3% CI 54.1-57.6]) scores compared to participants taking ethosuximide (46.5 [98.3% CI 43.4-49.6]; 45.8 [98.3% CI 42.9-48.7]; 54.6 [98.3% CI 52.4-56.9]; 53.0 [98.3% CI 51.3-54.8]). Lack of seizure freedom and elevated week 16-20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3% CI 55.6-60.3]) compared to participants taking ethosuximide (54.5 [95% CI 52.1-56.9])., Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE., Clinicaltrialsgov Identifier: NCT00088452., Classification of Evidence: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine., (© 2017 American Academy of Neurology.)

One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity. Our results have demonstrated that an early long-term treatment with fingolimod (1 mg/kg/day), started before absence seizure onset, has both antiepileptogenic and antidepressant-like effects in WAG/Rij rats. However, these effects were transitory, as 5 months after treatment discontinuation, both absence seizure and depressive like-behavior returned to control levels. Furthermore, a temporary reduction of mTOR signaling pathway activity, indicated by reduced phosphorylated mammalian target of rapamycin and phosphorylated p70S6k levels, and by increased phosphorylated Akt in WAG/Rij rats of 6 months of age accompanied the transitory antiepileptogenic effects of fingolimod. Surprisingly, fingolimod has demonstrated longer-lasting positive effects on cognitive decline in this strain. This effect was accompanied by an increased acetylation of lysine 8 of histone H4 (at both 6 and 10 months of age). In conclusion, our results support the antiepileptogenic effects of fingolimod. However, the antiepileptogenic effects were transitory. Moreover, fingolimod might also have a positive impact on animal behavior and particularly in protecting the development of memory decline.

Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neural circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3.2 T-type calcium channel gene. Thus, the objective of this study was to examine the effects of the clinical stage pan-T-type calcium channel blocker, Z944, on sociability behaviour in male and female GAERS and non-epileptic control (NEC) animals. Female GAERS showed reduced sociability in a three-chamber sociability task whereas male GAERS, male NECs, and female NECs all showed a preference for the chamber containing a stranger rat. In drug trials, pre-treatment with 5mg/kg of Z944 normalized sociability in female GAERS. In contrast, female NECs showed impaired sociability following Z944 treatment. Dose-dependent decreases in locomotor activity were noted following Z944 treatment in both strains. Treatment with 10mg/kg of Z944 altered exploration such that only 8 of the 16 rats tested explored both sides of the testing chamber. In those that explored the chamber, significant preference for the stranger rat was observed in GAERS but not NECs. Overall, the data suggest that T-type calcium channels are critical in regulating sociability in both GAERS and NEC animals. Future research should focus on T-type calcium channels in the treatment of sociability deficits observed in disorders such as CAE., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Typical absence seizures are observed in various epilepsy syndromes, however, few series have focused on early-onset absence epilepsy (EOAE). We aimed to evaluate the occurrence of this seizure type in children under 4 years of age in order to evaluate their electroclinical characteristics and outcome. We retrospectively studied (2006-2014) the electroclinical features of children with normal development and typical absence seizures starting before the age of 4 (with available pre-treatment video-EEG). Nine patients were included. Among them, eight patients had rhythmic myoclonic jerks involving the muscles of the upper face (eyebrows and eyelids) or neck, present from the onset to the end of the typical absence discharge. The myoclonia were synchronous with spike-wave complexes. One patient with GLUT-1 deficiency was refractory to antiepileptic polytherapy. The other eight became seizure-free; five with one antiepileptic drug and three with a combination of two drugs. The treatment was successfully withdrawn in five of the six patients who achieved two years of seizure freedom. None of them exhibited any other seizure type. Four of the eight patients with normal schooling required some support. We observed a positive correlation between the duration of absence seizure and the age of the patient at examination. Most of the patients under four years with only typical absence seizures had EOAE, and the motor symptoms may represent a distinctive age-related feature of EOAE. Further investigations are required to better correlate the role of brain maturation with the duration of the absence. [Published with video sequence on www.epilepticdisorders.com].

Aim: Childhood absence epilepsy (CAE) and benign childhood epilepsy with centrotemporal spikes (BECTS) are the most common forms of childhood epilepsy. Recent studies in animal models suggest that the two phenotypes may represent a neurobiological continuum. Although the coexistence of CAE and BECTS has been reported, this issue remains controversial. The purpose of this study was to analyse the electro-clinical characteristics of a group of children with contemporary or subsequent features of absence seizures and focal seizures consistent with BECTS., Material and Methods: A systematic record review from 8 epilepsy centres was used to identify 11 subjects, 5 females and 6 males, with electro-clinical documented consecutive or contemporary coexistence of CAE and BECTS., Results: Patient's age ranged between 7.8 and 17.3 years. Four out of 11 patients presented concomitant features of both syndromes, whereas the remaining 7 experienced the two syndromes at different times., Conclusions: Although CAE and BECTS are clearly defined syndromes and considered very different in terms of their pathophysiology, they share some features (such as similar age of onset, overall good prognosis), and can occur in the same patient. The long term prognosis of these patients seems to be good with an excellent response to anticonvulsant therapy., (Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objective: Perampanel (PER), a selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonist, exhibits broad-spectrum anticonvulsant activity in several seizure models, but its potential disease-modifying effects have not been investigated. Because of the relevance of AMPA receptors in epileptogenesis and psychiatric comorbidities, we studied the effects of PER in the WAG/Rij rat model of epileptogenesis, absence epilepsy, and depressive-like comorbidity., Methods: We investigated the effects of acute, subchronic, and chronic treatment with PER (0.25-3 mg/kg) on absence seizures, their development, and related psychiatric/neurologic comorbidity in WAG/Rij rats. Depression-related behavior was studied by using the forced swimming and the sucrose preference test; anxiety-related behavior by using the open field and elevated plus maze test; and memory by using the passive avoidance test., Results: PER (3 mg/kg/day orally for 17 weeks starting from P30) significantly reduced the development of absence seizures at 6 months of age (1 month after treatment withdrawal), but this effect was not maintained when reassessed 4 months later. Attenuated absence seizure development was accompanied by reduced depressive-like behavior in the forced swimming test (FST), whereas no effects were observed on anxiety-related behavior and memory. Subchronic (1 and 3 mg/kg/day orally for 1 week) and acute PER (0.25-1 mg/kg, i.p.) dosing did not affect established absence seizures and behavior., Significance: These results suggest that AMPA receptors are involved in mechanisms of epileptogenesis in an established model of absence epilepsy, and that these mechanisms differ from those responsible for seizure generation and spread when epilepsy has become established., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Background: The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared., Methods: In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6-19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3-4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses., Findings: 93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11-0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08-0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01-0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0-30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0-24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4-19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0-5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment., Interpretation: Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures., Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome accounting for 10% of all pediatric epilepsies. The aim of this review is to provide an updated overview of this epilepsy syndrome to pediatricians. Most of the patients can be initially managed in private practice or in general pediatric settings. Absence seizures are the only seizure type observed at the time of diagnosis in these patients. An electroencephalogram recording and a clinical evaluation lead to the diagnosis. The underlying mechanisms are not yet fully understood. CAE is considered a self-limited epilepsy syndrome since most of the patients will become seizure free. Only a few patients (5-10%) have resistant CAE. However, CAE, as well as any pediatric epilepsy syndrome, should not be considered a "benign" epilepsy. Attention deficit is observed in about one third of the patients. There is also an increased risk of academic difficulties related to specific cognitive disorders. Therefore, the early detection of children at risk of developing neuropsychological problems can be helpful for preventing school underachievement and poor psychosocial outcome. Recently, several studies including a large randomized controlled trial indicated that ethosuximide should be considered as a first-line treatment and valproate as a second-line treatment. Cognitive side effects should be an important factor in the selection of the antiepileptic drug and should be specifically assessed during the follow-up. This review concludes by discussing the criteria that might lead to referring the patient to a specialist., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: The objective was to identify unique features of the photoparoxysmal response seen in patients with neuronal ceroid lipofuscinosis type 2 as compared to patients with a photoparoxysmal response associated with other epilepsy syndromes., Methods: Electroencephalograms from patients with neuronal ceroid lipofuscinosis type 2 seen at the authors' institution in the past 10 years as well as electroencephalograms (EEGs) reported to have a photoparoxysmal response during a single year were reviewed., Results: A photoparoxysmal response was seen in 60% of the patients with neuronal ceroid lipofuscinosis type 2. This was most commonly seen with low frequency intermittent photic stimulation (76%) which often occurred in a time-locked fashion (63%) and was seen on the patient's initial EEG (78%). A unique pattern the authors called "sentinel" discharge was identified in 30% of EEGs in patients with neuronal ceroid lipofuscinosis., Conclusions: Photoparoxysmal responses in patients with neuronal ceroid lipofuscinosis type 2 have features which are distinguishing from photoparoxysmal responses seen in other epilepsies., (© The Author(s) 2016.)

Sudden unexpected death in epilepsy (SUDEP) is the leading cause for death in individuals with epilepsy. The frequency of SUDEP correlates with the severity of epilepsies and lack of response to antiepileptic drug treatment, but the underlying mechanisms of SUDEP have not been elucidated fully. GABRG2(Q390X) is a mutation associated with the epileptic encephalopathy Dravet syndrome (DS) and with genetic epilepsy with febrile seizures plus (GEFS+) in patients. The Gabrg2(+/Q390X) knockin (KI) mouse phenocopies the major features of DS and GEFS+ and has SUDEP throughout life. The Gabrg2(+/-) knockout (KO) mouse is associated with infrequent absence seizures and represents a model of mild absence epilepsy syndrome without increased mortality. To explore the basis for SUDEP in DS and GEFS+, we compared mutant γ2 subunit and wild-type α1 and β2/3 subunit expression in mice in brainstem nuclei associated with respiratory function including the solitary tract, pre-Botzinger complex and Kolliker-Fuse nuclei. We found that synaptic GABAA receptors were reduced while intracellular nonfunctional γ2(Q390X) subunits were increased in the heterozygous DS and GEFS+ KI mice, but not in the heterozygous absence epilepsy KO mice. Given the critical role of these nuclei in cardiorespiratory function, it is likely the impaired GABAergic transmission and neuronal dysfunction in these brainstem nuclei are involved in the cardiorespiratory collapse in SUDEP. The study provides novel mechanistic insights into cardiorespiratory failure of SUDEP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We report expression system-dependent effects of heterozygous mutations (P769L and A1059S) in the Cav3.2 CACNA1H gene identified in a pediatric patient with chronic pain and absence seizures. The mutations were introduced individually into recombinant channels and then analyzed by means of electrophysiology. When both mutants were co-expressed in tsA-201 cells, we observed a loss of channel function, with significantly smaller current densities across a wide range of voltages (-40 to +20 mV). In addition, when both mutant channels were co-expressed, the channels opened at a more depolarizing potential with a ~5-mV right shift in the half-activation potential, with no changes in half-inactivation potential and the rate of recovery from inactivation. Interestingly, when both mutants were co-expressed in the neuronal-derived CAD cells in a different extracellular milieu, the effect was remarkably different. Although not statistically significant (p < 0.07), current densities appeared augmented compared to wild-type channels and the difference in the half-activation potential was lost. This could be attributed to the replacement of extracellular sodium and potassium with tetraethylammonium chloride. Our results show that experimental conditions can be a confounding factor in the biophysical effects of T-type calcium channel mutations found in certain neurological disorders.

Rufinamide (RFD) is a novel drug that was recently approved as an adjunctive treatment for Lennox-Gastaut syndrome. Despite its reported effectiveness in generalized seizures (tonic, atonic, or tonic-clonic) in this syndrome, few data on its use in idiopathic generalized epilepsy are available. Indeed, the scientific evidence to date is limited to anecdotal cases or isolated clinical experiences. We report an uncommon, though paradigmatic, case of a woman affected by juvenile absence epilepsy (JAE) who, following a prolonged seizure-freedom period and the consequent withdrawal of valproate, presented a seizure relapse accompanied by a worsening in her electroclinical pattern. In view of this atypical evolution of JAE, characterized by drug-resistant seizures (absence and generalized tonic-clonic) and the progressive increase in electroencephalographic (EEG) abnormalities, several antiepileptic drugs were used, though to no benefit. The use of RFD instead led to a gradual control of the seizures and normalization of the EEG findings. In addition to this clinical experience, we briefly review the literature on the use of RFD in refractory generalized epilepsy., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Objective: Even if considered benign, absence epilepsy may alter memory and attention, sometimes subtly. Very little is known on behavior and cognitive functions in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model of absence epilepsy. We focused on different memory systems and sustained visual attention, using Non Epileptic Controls (NECs) and Wistars as controls., Methods: A battery of cognitive/behavioral tests was used. The functionality of reference, working, and procedural memory was assessed in the Morris water maze (MWM), 8-arm radial maze, T-maze and/or double-H maze. Sustained visual attention was evaluated in the 5-choice serial reaction time task., Results: In the MWM, GAERS showed delayed learning and less efficient working memory. In the 8-arm radial maze and T-maze tests, working memory performance was normal in GAERS, although most GAERS preferred an egocentric strategy (based on proprioceptive/kinesthetic information) to solve the task, but could efficiently shift to an allocentric strategy (based on spatial cues) after protocol alteration. Procedural memory and visual attention were mostly unimpaired., Significance: Absence epilepsy has been associated with some learning problems in children. In GAERS, the differences in water maze performance (slower learning of the reference memory task and weak impairment of working memory) and in radial arm maze strategies suggest that cognitive alterations may be subtle, task-specific, and that normal performance can be a matter of strategy adaptation. Altogether, these results strengthen the "face validity" of the GAERS model: in humans with absence epilepsy, cognitive alterations are not easily detectable, which is compatible with subtle deficits., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures.

Behavioural, neurological, and genetic similarities exist in epilepsies, their psychiatric comorbidities, and various psychiatric illnesses, suggesting common aetiological factors. Rodent models of epilepsy are used to characterize the comorbid symptoms apparent in epilepsy and their neurobiological mechanisms. The present study was designed to assess Pavlovian fear conditioning and latent inhibition in a polygenetic rat model of absence epilepsy, i.e. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the non-epileptic control (NEC) strain. Electrophysiological recordings confirmed the presence of spike-wave discharges in young adult GAERS but not NEC rats. A series of behavioural tests designed to assess anxiety-like behaviour (elevated plus maze, open field, acoustic startle response) and cognition (Pavlovian conditioning and latent inhibition) was subsequently conducted on male and female offspring. Results showed that GAERS exhibited significantly higher anxiety-like behaviour, a characteristic reported previously. In addition, using two protocols that differed in shock intensity, we found that both sexes of GAERS displayed exaggerated cued and contextual Pavlovian fear conditioning and impaired fear extinction. Fear reinstatement to the conditioned stimuli following unsignalled footshocks did not differ between the strains. Male GAERS also showed impaired latent inhibition in a paradigm using Pavlovian fear conditioning, suggesting that they may have altered attention, particularly related to previously irrelevant stimuli in the environment. Neither the female GAERS nor NEC rats showed evidence of latent inhibition in our paradigm. Together, the results suggest that GAERS may be a particularly useful model for assessing therapeutics designed to improve the emotional and cognitive disturbances associated with absence epilepsy., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Aim: Childhood absence epilepsy (CAE) is a paediatric epilepsy syndrome characterized by typical absence seizures in school age children. Although it is commonly considered to have a good prognosis, with a good response to antiepileptic drugs, recent studies questioned this traditional view of a “benign” disorder, in particular regarding neuropsychological functioning. The aim of this study is to review the neuropsychological involvement in patients affected by CAE., Methods: A literature search was carried out in PubMed's and Medline's databases for all relevant studies published between 1924 and 2014. The keywords used were neuropsychology, absence seizures, and CAE. Specific review articles, systematic reviews, textbooks and case reports were examined for any further publications., Results: In intellectual functioning, CAE patients seem to perform worse than healthy children, even if their IQ scores fall within the normal range. Similarly, CAE seems to affect verbal skills and learning. Executive functions have been reported to be mildly impaired. Data regarding memory are still conflicting., Discussion: Given the neuropsychological deficits in many CAE patients which significantly affect their quality of life, CAE should not be considered entirely “benign”. An early identification of neuropsychological dysfunction in CAE children is essential for appropriate treatment.

Background: To evaluate evidence and prognosis of refractory cases of absence seizures., Methods: Subjects with refractory absence seizures were identified retrospectively in 17 Italian epilepsy pediatrics Centers. We analyzed age at onset, family history, presence of myoclonic components, seizure frequency, treatment with antiepileptic drugs (AEDs), interictal electroencephalography (EEG) and neuropsychological assessment. Two subgroups were identified: one with patients with current absence seizures and another with patients that had become seizure free with or without AED treatment. The chi-square test was applied., Results: A total of 92 subjects with drug-resistant absence seizures were analyzed. 45 subjects still show absence seizures (49%) and the other 47 became seizure free (51%) after a period of drug-resistance. The statistical analysis between these two groups showed no correlation between age of onset, family history and abnormalities at interictal EEG. Statistically significant differences were observed with regard to the number of AEDs used and intellectual disability., Conclusion: Typical absence epilepsy classifiable as Childhood Absence Epilepsy could not be considered so "benign", as suggested in literature. A longer duration of disease and a higher frequency of seizure seem to be correlated with a higher presence of cognitive impairment. No significant risk factor was observed to allow the faster and better recognition of patients with worse prognosis., (Copyright © 2015. Published by Elsevier Ltd.)

Growing numbers of evidence indicate that cognitive impairments are part of clinical profile of childhood absence epilepsy. Little is known on neuropathological changes accompanied by cognitive deficits in absence epilepsy. The aim of the present study was to investigate age-dependent neuropathological changes accompanied by learning and memory impairments in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The learning and memory performances were assessed using passive avoidance paradigm and neuropathological alterations were investigated by the evaluation of the number of dark neurons and apoptotic cells as well as the expression of caspase-3 in the neocortex, the hippocampus, and different regions of the thalamus. Results revealed a decline in learning and spatial memory of 6-month-old WAG/Rij rats compared to age-matched Wistar rats as well as 2-month-old WAG/Rij and Wistar rats. The mean number of dark neurons was significantly higher in the hippocampal CA1 and CA3 areas as well as in the laterodorsal, centromedial, and reticular thalamic nuclei and the somatosensory cortex of 6-month-old WAG/Rij rats. In addition, a higher number of apoptotic cells as well as a higher expression of caspase-3 was observed in the hippocampal CA1 and CA3 regions, the laterodorsal thalamic nucleus, and the somatosensory cortex of 6-month-old WAG/Rij rats compared to other animal groups. These results indicate significant enhancement of neuronal damage and cell death accompanied by memory deficits after seizure attacks in a rat model of absence epilepsy. Seizure-induced neuronal injury and death may underlie cognitive impairments in absence epilepsy., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia., Objectives: Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer's cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia., Methods: We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.7) and average intelligence and compared them with 89 age-, gender- and class-matched healthy children (mean age 10.57) using tests for handwriting fluency and quality, based on which we divided patients and controls into four subgroups: AE/dysgraphia, AE without dysgraphia, controls with dysgraphia and healthy controls. We compared the blink reflex recovery cycle in children belonging to all four subgroups., Results: We identified dysgraphia in 17/82 children with AE and in 7/89 controls (20.7 vs 7.8%; P = 0.016) with the former having a 3.4-times higher risk of dysgraphia regardless of age and gender (odd ratio: 3.49; 95% CI 1.2, 8.8%). The AE/dysgraphia subgroup performed worse than controls with dysgraphia in one test of handwriting fluency (P = 0.037) and in most trials testing handwriting quality (P< 0.02). In children with AE/dysgraphia the blink reflex showed no suppression at short interstimulus intervals, with a difference for each value emerging when comparing the study group with the three remaining subgroups (P<0.001)., Conclusions: In children with AE, dysgraphia is highly prevalent and has a homogeneous, distinctive pathophysiological substrate consistent with idiopathic dystonia.

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 CaV 3.2 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., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

We report a 12-year-old female patient with a mild phenotype of glucose transporter type 1 deficiency syndrome (Glut1D). The clinical picture was characterized by refractory absence epilepsy, migraine, and learning disabilities. Absence seizures appeared at the age of 4 years, and electroencephalogram (EEG) showed irregular discharges of diffuse epileptic abnormalities. During the follow-up, seizures became drug resistant, cognitive evaluation revealed learning difficulties, and the patient complained migraine episodes. The evidence of seizure worsening before meals and the drug resistance suggested a Glut1D. Molecular analysis of SLC2A1 gene showed the presence of a pathogenic de novo mutation of the gene in heterozygosity (p.Ala275Thr, c.823G > A). Our case and the review of literature data on patients with Glut1D and absences provide a combination of clinical and EEG keys that should prompt the genetic analysis. The Glut1D should be suspected when absence seizures are associated with at least one among: irregular ictal EEG discharges, mild mental retardation, migraine, microcephaly, drug resistance, and worsening during fasting. An early diagnosis allows to establish one of the available ketogenic regimens which could modify the natural history of this treatable condition., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a genetic model, derived from Wistar rats by selective breeding. In all previous studies, GAERS were compared to their paired selected strain not expressing spike-and-wave discharges (SWDs), namely nonepileptic controls (NECs). Because the occurrence/absence of SWDs is of polygenic origin, some other traits could have been selected along with occurrence/absence of SWDs. Therefore, we explored the importance of using a second control group consisting in Wistar rats, the strain of origin of GAERS, in addition to NECs, on locomotion and anxiety in GAERS., Methods: A test battery encompassing home-cage, open-field, beam-walking and elevated plus-maze evaluations was used. In addition, stereologic analyses were performed to assess the volume of thalamus, amygdala, and hippocampus. The occurrence/absence of SWDs was determined in all three strains by electroencephalography (EEG) recording., Results: When compared to NECs and Wistars, GAERS displayed lower exploratory activity and fastened habituation to novelty. In the plus-maze, scores of GAERS and Wistars were similar, but NECs appeared significantly less anxious (possibly in association with increased amygdala volume); evidence for weaker anxiety in NECs was also found in the open-field evaluation. The volumetric study revealed increased thalamic volume in GAERS compared to both control groups. SWDs were present in all GAERS and in 80% of Wistars., Significance: Compared to the original Wistar strain as an additional control group, the selective breeding that generated the GAERS has no incidence on anxiety-related behavior, conversely to the selection of SWD suppression in NECs, in which anxiety is attenuated. These findings point to the importance of using a second control group composed of Wistar rats in studies characterizing the behavioral profile of GAERS. Thereby, possible confusions between occurrence/absence of SWDs and other features that come along with selection and/or differential brain development induced by the genetic mutations are reduced., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

We report on a 25 year old female patient who had a diagnosis of Jeavons syndrome since her childhood. Although valproate led to seizure freedom, she developed persistent reproductive endocrine disorders attributed to this drug. The withdrawal of valproate in parallel with an initiation of levetiracetam monotherapy resulted in a maintenance of clinical remission and a resolution of these abnormalities. This case together with relevant literature data supports the view that the use of levetiracetam might be of benefit for female patients with Jeavons syndrome., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Childhood absence epilepsy (CAE) is defined by absence seizures in a normally developing child, with onset between 4 and 10 years of age.(1) Typical absence seizures consist of behavioral arrest with or without automatisms, usually last 30-60 seconds, and demonstrate a characteristic 3-Hz generalized spike-wave (GSW) pattern on EEG, often in response to hyperventilation.(2) Children may have hundreds of episodes daily, many of them subclinical, which can impair sustained attention and memory processing. There is a strong association between CAE and disorders of attention and executive function. This association persists even when seizures are well-controlled. An underlying structural or functional abnormality of the brain has been postulated to explain both observations.(3,4) This article by Dlugos et al.(5) is a post hoc analysis of a randomized, double-blinded trial(6) that seeks to characterize the relationship between EEG characteristics prior to treatment, measures of attention, and the outcome of initial antiepileptic treatment.

Age-dependent increase of seizure activity at absence epilepsy exacerbates hemodynamic and autonomic regulation of heart rate. Cardiac dysfunction is accompanied by an increasing duration of intervals repolarization left ventricular QTc, which causes the risk of life-threatening arrhythmias, increases the threat of sudden cardiac death. Anticonvulsant drug therapy provides an opportunity to improve the functional state of the cardiovascular system, if not exceeded a certain level of seizure activity of the brain. This possibility remains as long as the progressive seizure activity isn't reaches a certain level. Later anticonvulsant drug therapy reduces seizure activity of the brain, but does not improve the functional state of heart.

Background: Antiepileptics may affect cortisol metabolism through CYP3A4. There is little known about ethosuximide., Clinical Case: Our patient is a 12-year-old girl with salt-wasting congenital adrenal hyperplasia (CAH) owing to 21 hydroxylase deficiency. A standard treatment regimen was initiated with satisfactory results until the age of 6 years, when she developed absence seizures treated with ethosuximide. She received such therapy until the age of 12 years, at which point ethosuximide was discontinued. During ethosuximide administration, she experienced worsening control of CAH disease activity that responded to progressive increases in hydrocortisone dose up to 28 mg/m2 per day. Despite high doses of hydrocortisone, she suffered no cushingoid symptoms. Her requirements for high glucocorticoid replacement doses resolved shortly after ethosuximide was discontinued. We provide data over 6 years demonstrating a correlation between adrenal hormone secretion, cortisol requirements and ethosuximide dose., Conclusion: This is the first case demonstrating an interaction between ethosuximide and hydrocortisone clearance in the treatment of salt-wasting CAH.

Neurophysiological and neuroimaging studies including both patients with disorders of consciousness and healthy subjects with modified states of consciousness suggest a crucial role of the medial posteroparietal cortex in conscious information processing. However no direct neuropsychological evidence supports this hypothesis and studies including patients with restricted lesions of this brain region are almost non-existent. Using direct intraoperative electrostimulations, we showed in a rare patient that disrupting the subcortical connectivity of the left posterior cingulate cortex (PCC) reliably induced a breakdown in conscious experience. This acute phenomenon was mainly characterized by a transient behavioral unresponsiveness with loss of external connectedness. In all cases, when he regained consciousness, the patient described himself as in dream, outside the operating room. This finding suggests that functional integrity of the PPC connectivity is necessary for maintaining consciousness of external environment., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Jeavons syndrome (JS) is one of the underreported epileptic syndromes and is characterized by eyelid myoclonia (EM), eye closure-induced seizures or electroencephalography (EEG) paroxysms, and photosensitivity. In the Western populations, it has been reported to be characterized by focal posterior, occipital predominant epileptiform discharges (OPEDs) or frontal predominant epileptiform discharges (FPEDs) followed by generalized EDs in both interictal and ictal EEG recordings. However, it is not clear if there are different clinical manifestations between OPEDs and FPEDs. The clinical and electrographic presentations in the Chinese population are largely unknown. Here, we report the clinical and electroencephalographic features of 50 Chinese patients with JS and evaluate for the presence of different clinical features between patients with OPEDs and patients with FPEDs., Methods: We identified 50 cases who met the Jeavons syndrome criteria from 4230 patients with epilepsy at Xijing Hospital, Xi'an, China from the period of January 2010 to November 2011. These patients underwent long-term 24-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI) or computerized tomography (CT). Webster IQ testing was performed to determine intellectual development. We reviewed and described the interictal abnormalities, ictal EEG pattern, and demographic, clinical, and neuroimaging findings of these 50 Chinese patients in Xi'an. We divided the 50 patients into two groups according to the predominance of EDs and analyzed their clinical features., Results: Twenty-five of these 50 patients were male. Twenty-two out of 32 patients in the group with FPEDs were male, and 3/18 patients in the group with OPEDs were male. The median age of EMA-EM onset in FPEDs was 8years and that in OPEDs was 5.8years. Eyelid myoclonia occurred in all the 50 patients. Twenty-one out of 32 patients in the group with FPEDs had EM with absences, and 14/32 of them had EM with eyeball rolling up. Two out of 18 patients in the group with OPEDs had EM with absences, and only 1 of 18 had EM with eyeball rolling up., Conclusion: Eyelid myoclonia with or without absences or JS diagnosis is easily missed and underreported in China. As an IGE, either the frontal or the occipital lobe may initiate generalized spike-and-wave discharges (GSWDs) and generalized seizures (GSs). There may be two subtypes of JS with distinctive clinical and electroencephalogrphic features: a predominantly male group with frontal predominant epileptiform discharges, eyelid myoclonia, and eyes rolling up and a predominantly female group with occipital predominant epileptiform discharges with eyelid myoclonia alone., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Specific cognitive deficits have been identified in children with epilepsy irrespective of results on intelligence tests. Memory deficits are traditionally attributed to temporal lobe epilepsy, whereas the impact of frontal lobe epilepsy on memory functions has remained controversial. The aim of this study was the examination of memory abilities in other childhood common epilepsy syndromes (frontal lobe epilepsy (FLE), childhood absence epilepsy (CAE), and benign epilepsy with centrotemporal spikes (BECTS)) and the influence of epilepsy-related variables. Memory was examined in 90 children with epilepsy (each epilepsy group consisted of 30 children), aged 6-15, and compared with 30 control children. Children with FLE showed significant deficits in verbal and visual memory. In addition, type of epilepsy, earlier age at epilepsy onset, and longer active duration of epilepsy were associated with memory problems. Seizure frequency and treatment, however, did not influence memory performance. This study indicates that children with FLE show greater risk of developing memory deficits than children with CAE or BECTS, thus highlighting the importance of assessing also memory functions in frontal lobe epilepsy.