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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.

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.)

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.)

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.)

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.

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.)

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.

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.)

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.)

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.

Purpose: Eyelid myoclonia with absences (EM) is an uncommon type of absence seizure associated with a variety of epilepsy syndromes. The syndrome of epilepsy with EM (EMA) has been proposed to denote the onset of frequent EM induced by eye closure and photic stimulation beginning in childhood. The clinical genetics of EMA has not been well characterized, although a family history of seizures is not infrequent., Methods: Individuals with EMA were ascertained by referral and through the investigators' clinical practices. All available family members were assessed for seizures using a validated seizure questionnaire. Electroclinical data were obtained on each proband and all affected family members; pedigrees were constructed. Families were analyzed for phenotypic patterns., Key Findings: Eighteen individuals with EMA were recruited. A history of seizures was found in 34 relatives in 15 (83%) of 18 families. In terms of epilepsy syndromes, 9 relatives from 7 of 15 families had febrile seizures. Two relatives had EMA. Classical genetic generalized epilepsy (GGE) syndromes were seen in five relatives: two generalized tonic-clonic seizures alone, two childhood absence epilepsy (CAE), and one juvenile myoclonic epilepsy (JME). Genetic epilepsy with febrile seizures plus (GEFS+) phenotypes occurred in 16 relatives. On review of the epilepsy syndromes within each family, seven families had a pattern consistent with GEFS+, whereas three families had classical GGE., Significance: The clinical genetics of EMA is suggestive of complex inheritance with shared genetic determinants overlapping with both classical GGE and GEFS+. The epilepsy syndromes in relatives of probands with EMA differ from those found in families of probands with CAE, supporting the concept that patients with EMA have a syndrome that is distinct from CAE. This presumably reflects different genetic components contributing to their genetic architecture., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization-related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles., Methods: Fifty-one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within-group analyses were also conducted to examine seizure-related factors that may be related to neuropsychological test performance., Key Findings: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another., Significance: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Childhood absence epilepsy (CAE) and benign childhood epilepsy with centrotemporal spikes (BCECTS), or benign rolandic epilepsy (BRE), are the most common forms of childhood epilepsy. CAE and BCECTS are well-known and clearly defined syndromes; although they are strongly dissimilar in terms of their pathophysiology, these functional epileptic disturbances share many features such as similar age at onset, overall good prognosis, and inheritance factors. Few reports are available on the concomitance of CAE and BCECTS in the same patients or the later occurrence of generalized epilepsy in patients with a history of partial epilepsy. In most cases described in the literature, absence seizures always started after the onset of benign focal epilepsy but the contrary has never occurred yet. We describe two patients affected by idiopathic generalized epileptic syndrome with typical absences, who experienced BCECTS after remission of seizures and normalization of EEG recordings. While the coexistence of different seizure types within an epileptic syndrome is not uncommon, the occurrence of childhood absence and BCECTS in the same child appears to be extremely rare, and this extraordinary event supports the hypothesis that CAE and BCECTS are two distinct epileptic conditions. However, recent interesting observations in animal models suggest that BCECTS and CAE could be pathophysiologically related and that genetic links could play a large role., (Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Absence seizures consist of a brief and sudden impairment of consciousness. They are characterized by bilaterally synchronized spike and wave discharges (SWDs), which reflect abnormal oscillations in the thalamocortical loops. Recent studies have suggested that the basal ganglia are involved in generation of the SWDs, but their roles are poorly understood at the molecular and cellular levels. Here we studied the pathophysiological roles of the basal ganglia, using in vivo and in vitro measurements of tottering mice, a well-established model of absence epilepsy. We found that the membrane excitability in subthalamic nucleus (STN) neurons was enhanced in tottering mice, which resulted from reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. Pharmacological blockade and activation of HCN channel activity in vitro bidirectionally altered the membrane excitability of the STN neurons. Furthermore, these pharmacological modulations of HCN channel activity in the STN in vivo bidirectionally altered the mean SWD duration. In addition, STN deep brain stimulation modulated SWDs in a frequency-dependent manner. These results indicate that STN is involved in the rhythm maintenance system of absence seizures.

15q13.3 microdeletions are the most common genetic findings identified in idiopathic generalized epilepsies to date, and they are present in up to 1% of patients. In addition, 15q13.3 microdeletions have been described in patients with epilepsy as part of a complex neurodevelopmental phenotype. We analyzed a cohort of 570 patients with various pediatric epilepsies for 15q13.3 microdeletions. Screening was performed using quantitative polymerase chain reaction; deletions were confirmed by array comparative genomic hybridization (CGH). We carried out detailed phenotyping of deletion carriers. In total, we identified four pediatric patients with 15q13.3 microdeletions, including one previously described patient. Two of four deletions were de novo, one deletion was inherited from an unaffected parent, and for one patient the inheritance is unknown. All four patients had absence epilepsy with various degrees of intellectual disability. We suggest that absence epilepsy accompanied by intellectual disability may represent a common phenotype of the 15q13.3 microdeletion in pediatric patients with epilepsy., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: Depression is most commonly associated with epilepsy. Recent reports have suggested a putative relationship between seizure development and onset of depressive behavior, whereas others proposed that two clinical entities might represent different neuropathologic aspects of the same neurologic disorder. The WAG/Rij rat absence epilepsy model has also been proposed as a suitable model to test antidepressant drugs. We previously reported on a long-term study of two antiepileptic drugs (AEDs) to assess their protective role in absence epileptogenesis. Here, we examined the effects of long-term treatment with several AEDs on absence seizure development and onset of depressive-like behavior in WAG/Rij rats at different ages, using a forced swimming test (FST)., Methods: Animals were divided into one untreated control group and four test groups, given ethosuximide, levetiracetam, zonisamide, or carbamazepine. Electroencephalography (EEG) readings were recorded at 6.5 months of age., Key Findings: Ethosuximide-treated animals showed significant reductions in recorded spike-wave discharges (SWDs), and FST immobility time (IT) compared with untreated same age controls. However, zonisamide- and carbamazepine-treated animals had IT values similar to those of controls, but only zonisamide significantly decreased absence seizure development. Carbamazepine increased SWD incidence. Levetiracetam also protected against seizure development, while augmenting IT, suggesting a prodepressive effect., Significance: Although treatment with ethosuximide, levetiracetam, or zonisamide reduced appearance of SWDs in WAG/Rij rats, this was not generally linked to a reduced onset of depressive characteristics, as assessed by FST. Therefore, expression of depressive-like behavior seems unrelated to seizure control in this model. Some possible alternative explanations for the observed data are discussed., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

In this study, we used surface-based morphometry to examine whether age-related changes in gray matter tissue thickness and depth of sulcal regions at high spatial resolution across the cortex differed in children with childhood absence epilepsy (CAE) compared to healthy control subjects. In addition, the possibility of variable brain-cognition relationships in the CAE compared to the control group was investigated. The main findings of this study are as follows: (1) From the developmental perspective, children with CAE did not demonstrate the normal regional age-related changes involving a decrease in cortical thickness and increase in sulcal depth. (2) None of the seizure variables, including age of onset, seizure frequency, and AEDs had a significant effect on the association between age and cortical morphometry measures in the CAE population. (3) Even though the CAE group had mean VIQ and PIQ scores in the average range, our findings suggest that they use different brain regions to perform these cognitive functions compared to healthy controls. This first study on brain morphometry and cognition in children with childhood absence seizures has important implications for advancing our understanding of brain development and cognitive comorbidity in CAE, as well as for revisiting the clinical notion that CAE is a benign disorder., (Copyright © 2010 Wiley-Liss, Inc.)

The diagnosis of benign epilepsy syndrome should meet the following criteria: age-related and self-limited; good response to medication; and no obvious neurological sequelae after seizure. However, the current concept of benign epilepsy syndrome has been challenged because of the advancements in genetic studies, neuroimaging, and molecular techniques. Many studies have revealed that the prevalence of behavioral problems and learning difficulties as well as subtle cognitive deficits is higher among patients with benign epilepsy, compared with the normal population. Here, we review updated results of these studies to show the latest and broad comprehensive knowledge of benign epilepsy in children., (Copyright © 2011 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.)

We report an unusual association between idiopathic occipital epilepsy and childhood absence epilepsy in 2 pediatric patients. At first clinical and electroencephalographic evaluation, the patients presented the peculiar signs of idiopathic occipital epilepsy Gastaut type: focal sensory visual seizures, migraine-like symptoms (only in one patient) and unilateral spike-wave discharges over occipital regions. Both children were treated with valproic acid and their seizures were rapidly controlled. After a seizure-free period, the patients presented typical absence with ictal electroencephalographies showing 3 cycles/s generalized and symmetrical spike-wave complexes. We discuss the possible association between these two epileptic syndromes and its common pathophysiological mechanisms., (2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Eyelid myoclonia with absences (EMA), or Jeavons syndrome, is a generalized epileptic condition clinically characterized by eyelid myoclonia (EM) with or without absences, eye closure-induced electroencephalography (EEG) paroxysms, and photosensitivity; in addition, rare tonic-clonic seizures may also occur. Although first described in 1977 and widely reported by several authors within the last few years, EMA has not been yet recognized as a definite epileptic syndrome. However, when strict criteria are applied to the diagnosis, EMA appears to be a distinctive condition that could be considered a myoclonic epileptic syndrome, with myoclonia limited to the eyelids, rather than an epileptic syndrome with absences.

Purpose: To investigate the blood oxygenation level-dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function., Methods: Four patients with EMA were investigated through the method of EEG-fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored., Results: Seven sessions of EEG-fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges., Conclusions: The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations ("default" pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.

Purpose: We studied the electroclinical features and evolution in patients with childhood absence epilepsy (CAE) associated with electroencephalographic findings similar to those of benign focal epilepsies (BFE) with or without clinical manifestations compatible with these focal idiopathic syndromes., Methods: Between June 1994 and June 2002, we found 203 (3.6%) patients with typical electroclinical features of CAE among 8285 children with epilepsy. From this population of 203, we found 30 cases (14.7%) that also showed focal abnormalities of BFE on the EEG. Seven of these 30 cases also had clinical manifestations of BFE that preceded the onset of the absences., Results: There were 20 (66.5%) boys and 10 (33.5%) girls. Age at onset of absences ranged from 2 to 10.5 years, with a mean age of 5.5 years. Of 30, 7 had focal clinical seizures as well. Three of seven had seizures characteristic of Panayiotopoulos syndrome (PS), and the other four had seizures compatible with childhood occipital epilepsy (COE) of Gastaut. The focal seizures started between 3 and 7 years of age. In all patients seizures were under control within 2-24 months (mean: 11 months) after onset. The focal discharges disappeared in 26 patients at a mean age of 8 years (range 4-13 years), 1 year after the typical absences had disappeared. In four patients the focal paroxysms are still present., Conclusion: The association of two different idiopathic focal and generalized epilepsies in the same patient may be merely coincidental, but a close genetic relationship between both epileptic syndromes might be another hypothesis. Another explanation could be that our series of patients represent a subgroup of CAE.

This investigation examined psychopathology and IQ levels in 30 children with CSWS and 42 children with BRE and compared them with 40 healthy controls and 23 children with absence epilepsy by using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) and Wechsler Intelligence Test for Children (WISC-R). The CSWS and BRE groups had the highest rate of psychiatric diagnoses and lowest IQ scores. The BRE group had higher rates of psychopathology and lower IQ scores compared to the healthy controls. While BRE and absence groups did not differ with regard to presence of psychopathology, IQ levels and types of psychopathologies, children with CSWS had more psychiatric disorders and lower IQ scores compared to the patient group with absence epilepsy. These findings suggest that CSWS and BRE are two epileptic syndromes that lead to psychiatric disorders and lower IQ scores. Hence, psychiatric consultation should be a part of the treatment while managing these children.

The molecular basis of idiopathic generalized epilepsy remains poorly understood. Absence epilepsy with 3 Hz spike-wave EEG is one of the most common human epilepsies, and is associated with significant morbidity. Several spontaneously occurring genetic mouse models of absence epilepsy are caused by dysfunction of the P/Q-type voltage-gated calcium channel CaV2.1. Such mice exhibit a primary generalized spike-wave EEG, with frequencies in the range of 5-7 Hz, often associated with ataxia, evidence of cerebellar degeneration and abnormal posturing. Previously, we identified a single case of severe primary generalized epilepsy with ataxia associated with CaV2.1 dysfunction, suggesting a possible link between this channel and human absence epilepsy. We now report a family in which absence epilepsy segregates in an autosomal dominant fashion through three generations. Five members exhibit a combination of absence epilepsy (with 3 Hz spike-wave) and cerebellar ataxia. In patients with the absence epilepsy/ataxia phenotype, genetic marker analysis was consistent with linkage to the CACNA1A gene on chromosome 19, which encodes the main pore-forming alpha1A subunit of CaV2.1 channels (CaV2.1alpha1). DNA sequence analysis identified a novel point mutation resulting in a radical amino acid substitution (E147K) in CaV2.1alpha1, which segregated with the epilepsy/ataxia phenotype. Functional expression studies using human CACNA1A cDNA demonstrated that the E147K mutation results in impairment of calcium channel function. Impaired function of the brain calcium channel CaV2.1 may have a central role in the pathogenesis of certain cases of primary generalized epilepsy, particularly when associated with ataxia, which may be wrongly ascribed to anticonvulsant medication.

Recessive mutations in genes encoding voltage-gated Ca2+ channel subunits alter high-voltage-activated (HVA) calcium currents, impair neurotransmitter release, and stimulate thalamic low-voltage-activated (LVA) currents that contribute to a cortical spike-wave epilepsy phenotype in mice. We now report thalamic LVA current elevations in a non-Ca2+ channel mutant. EEG analysis of Coloboma (Cm/+), an autosomal dominant mutant mouse lacking one copy of the gene for a synaptosomal-associated protein (SNAP25) that interacts with HVA channels, reveals abnormal spike-wave discharges (SWDs) in the behaving animal. We compared the biophysical properties of both LVA and HVA currents in Cm/+ and wild-type thalamic neurons and observed a 54% increase in peak current density of LVA currents evoked at -50 mV from -110 mV in Cm/+ before the developmental onset of seizures relative to control. The midpoint voltage for steady-state inactivation of LVA currents in Cm/+ was shifted in a depolarized direction by 8 mV before epilepsy onset, and the mean time constant for decay of LVA Ca2+ currents at -50 mV was also prolonged. No significant differences were found in recovery from inactivation of LVA currents or in HVA current densities and kinetics. Our data demonstrate that a non-Ca2+ channel subunit gene mutation leads to potentiated thalamic LVA currents that precede the appearance of SWDs and that altered somatodendritic HVA currents are not required for abnormal thalamocortical oscillations. We suggest that presynaptic release defects shared by these mutants lead to postsynaptic LVA excitability increases in thalamic pacemaker neurons that favor rebound bursting and absence epilepsy.

Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS(+)) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS(+) and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.

This report describes atypical absence seizures induced by phenobarbital (PB) in a patient with benign childhood epilepsy with centrotemporal spikes. An 11-year-old girl had nocturnal motor seizures, beginning at the age of 7 years. Interictal EEG displayed centrotemporal sharp waves in the left and right sides alternatively, which increased significantly in frequency during sleep. She was given a diagnosis of benign childhood epilepsy with centrotemporal spike and was treated with valproic acid (VPA), which controlled her seizures for 3 years. She experienced nocturnal Rolandic seizures again, at the age of 10 years 2 months, 10 years 10 months in spite of the regular medication, and PB 60 mg daily was added to the VPA. Her parents noted de novo a few seconds of unresponsive fits 7 days after PB administration. Ictal EEG of the fits revealed diffuse irregular spike and wave bursts (1-4 seconds). VPA and PB in her blood was within the therapeutic ranges. After discontinuing PB, the atypical absence seizures immediately disappeared. Phenobarbital should be added to the list of drugs that potentially provoke de novo seizures., (Copyright 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.)

Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy. Nonlinear association analysis revealed a consistent cortical "focus" within the peri-oral region of the somatosensory cortex. The SWDs recorded at other cortical sites consistently lagged this focal site, with time delays that increased with electrode distance (corresponding to a mean propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more complex and could not account for the observed cortical propagation pattern. Cortical and thalamic sites interacted bi-directionally, whereas the direction of this coupling could vary throughout one seizure. However, during the first 500 msec, the cortical focus was consistently found to lead the thalamus. These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spike-wave discharges characteristic for absence seizures in the rat. Instead, the results suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and that the large-scale synchronization is mediated by ways of an extremely fast intracortical spread of seizure activity. Analogous mechanisms may underlie the pathophysiology of human absence epilepsy.

Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.

Antiepileptic drugs have been reported to have a variety of adverse effects on behavior and performance in children with epilepsy. Previous studies investigating these side effects, however, have not controlled for the baseline status of the child (e.g. underlying neurological condition, seizure type, socioeconomic status, family variables), making it difficult to determine whether changes in function are attributable to the use of medication. We investigated the cognitive and behavioral profiles of 43 children, aged from 4 to 16 years, with new onset, idiopathic seizures. Twenty-six of these children participated in a 6-month follow-up study, and 12 in a 12-month follow-up study, investigating the effects of antiepileptic medications on psychological functioning. The children were of average intelligence (mean IQ 108) and had not previously been treated with antiepileptic medication. Children were classified as having either generalized convulsive, generalized non-convulsive (absence), simple partial, or complex partial seizures. Prior to the initiation of treatment, children with partial seizures were found to perform better than children with generalized seizures on measures of cognitive functioning. Children with convulsive seizures obtained significantly higher cognitive scores than those with non-convulsive seizures. Children with generalized non-convulsive seizures had lower cognitive scores than subjects with other types of seizure. No differences were found between groups at baseline prior to the initiation of antiepileptic medications. Analysis of subjects' performance after 6 and 12 months of antiepileptic therapy showed no significant deterioration attributable to medication. The differences in cognitive performance of the four seizure groups at baseline were not apparent at the time of follow-up. These results indicate that intrinsic and environmental variables may play a more significant role in predisposing certain children to cognitive and learning problems than do antiepileptic medications.

While temporal lobe epilepsy is often considered in the differential diagnosis of patients with anxiety or panic disorders, other types of epilepsy can confound the presentation or treatment of adults with panic disorders. The cases of two patients are presented who were initially thought to have temporal lobe epilepsy producing panic attacks, but who were subsequently found to have primary generalized seizures. The clinical implications are discussed.

The pattern of occipital-posterotemporal spike-wave paroxysms (O-PT SWPs), is a distinctive EEG abnormality observed primarily with occipital epilepsy of childhood and basilar artery migraine. We studied EEG and clinical features in 30 children and young adults with this EEG pattern. Prolonged and brief O-PT SWPs were observed. Prolonged discharges (greater than 6 s) were observed only in children with seizures (p less than 0.001), and brief discharges (1-6 s) were observed immediately after eye closure. Generalized SWPs (11 patients, 37%) and background abnormalities (17 patients, 57%) were common. Photic activation of O-PT SWPs was not observed. Twenty-four patients (80%) manifested paroxysmal phenomena-seizures (20 patients, 67%) and migraine (12 patients, 40%, 4 alone and 8 with seizures). Fifteen patients (75%) had partial seizures, and 5 (25%) had absence seizures. In 7 patients with partial seizures, an etiology was evident. Neurologic examination was more often abnormal in patients with secondary partial seizures than in those with idiopathic partial seizures (p less than 0.05) and absence seizures. Conversely, migraine was more often associated with idiopathic partial seizures than with secondary partial seizures (p less than 0.05) and absence seizures. Six children (20%) had no paroxysmal events. Generalized SWPs were uncommon in patients with idiopathic partial seizures. We conclude that O-PT SWPs is a nonspecific epileptiform abnormality that may occur in children with (a) idiopathic partial, (b) symptomatic partial, and (c) absence epilepsies, but it may also occur in patients with no evidence of seizures.

We studied unilateral brief focal atonia (BFA) in seven patients with childhood partial epilepsy. BFA was observed as a transient dropping of one arm lasting from 100 to 150 ms when patients were asked to keep both arms outstretched in front of the body. Close examination using simultaneous video-polygraphic recordings showed dropping of the arm to correspond exactly with a single sharp and slow wave complex arising from the contralateral centrotemporoparietal region. The BFA occasionally would progress to atonic seizures or atonic absence seizures, when the localized epileptic discharge evolved into generalized discharges. In one patient we found a positive correlation between the intensity of BFA and the amplitude of the contralateral epileptic discharges. A higher amplitude corresponded to more pronounced BFA and a lower amplitude to less pronounced BFA. These results led us to conclude that the apparently interictal single sharp and slow wave complex in the rolandic region may inhibit contralateral motor control, thus producing BFA that corresponds with the spike amplitude.

Overall, children with epilepsy have poorer concentration and mental processing and are less alert than age-matched controls. The relationship between cognitive functioning and epilepsy is complex, however, with widely differing degrees of intellectual impairment--ranging from minimal to severe and progressive--related to diverse types of epileptic seizures, syndromes, and etiological factors. Prolonged and frequently repeated seizures are typically associated with more severe effects on cognitive functioning, particularly if epilepsy is symptomatic, i.e., secondary to a demonstrable brain lesion. A combination of such factors may contribute to the mental deterioration seen in many children suffering from severe epilepsy.

Absence epilepsy with multiple daily seizures and onset at the age of 6 and 1/2 months in a healthy female child with normal development is described. EEG-video recording revealed typical absence seizures (vacant staring and interruption of motor activity) and complex absences (as above, plus raising of the eyeballs, slight beatings of the eyebrows, and forward propulsion of head and shoulders). The absences were accompanied by bilateral symmetrical 3-Hz spike-wave discharges preceded, and at times followed, by bilateral frontoparietal theta activity coinciding with onset and termination of the absence seizures. The seizures regressed with nitrazepam therapy. At age 3-years, the child is seizure-free and shows normal neurologic development.

Simple acoustic stimuli were delivered at the onset of absence seizures in 23 investigations of 19 patients. In 79 of 139 observations, the stimulation promptly inhibited the seizure. The most effective inhibition was achieved in the first 3 s of the absence seizure. An automatic system of self-stimulation is recommended for further investigations. Following solution of some theoretical questions and technical problems, the suggested method can become a new therapeutic modality in seizure treatment.