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Dr. Masur and colleagues(1) from the Childhood Absence Epilepsy Study Group tried to answer a few important questions regarding childhood absence epilepsy (CAE) in their article "Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy." First, they wanted to know whether children with absence epilepsy have any problems with thinking before starting medications. If the children have problems with thinking, the authors wanted to identify the specific types of thinking problems the children have. The authors also wanted to assess what effect seizure medications have on attention in these children. In principle, medications could improve or worsen attention. The possible effects of medication on attention may or may not depend on whether the medications control the seizures.

Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine short-term differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine., Methods: Subjects with newly diagnosed CAE entering a double-blind, randomized controlled clinical trial had neuropsychological testing including assessments of general intellectual functioning, attention, memory, executive function, and achievement. Attention was reassessed at the week 16-20 visit., Results: At study entry, 36% of the cohort exhibited attention deficits despite otherwise intact neurocognitive functioning. Structural equation modeling of baseline neuropsychological data revealed a direct sequential effect among attention, memory, executive function, and academic achievement. At the week 16-20 visit, attention deficits persisted even if seizure freedom was attained. More subjects receiving valproic acid (49%) had attention deficits than subjects receiving ethosuximide (32%) or lamotrigine (24%) (p = 0.0006). Parental assessment did not reliably detect attention deficits before or after treatment (p < 0.0001)., Conclusions: Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted., Classification of Evidence: This study provides Class I evidence that valproic acid is associated with more significant attentional dysfunction than ethosuximide or lamotrigine in children with newly diagnosed CAE.

In this study we used EEG-fMRI to investigate whether peri-ventricular nodular heterotopia (PNH) are connected to the seizure generating network in individuals initially diagnosed with absence seizures (AS) who were later found to have co-existent PNH. We performed event related EEG-fMRI of the patients typical events as well as performing functional connectivity (FC) seeded from the PNH to answer this question. Both subjects demonstrated event related BOLD change in the "core" absence network. Subject 1 also displayed event related BOLD increase in the nodules while FC analysis demonstrated connectivity between the nodules and the thalami and striatum bilaterally. The second subject did not display event related BOLD in the PNH but FC analysis demonstrated strong connections between the PNH and the parietal cortex. This study demonstrates that the peri-ventricular nodules can show connectivity to the absence network in individuals with AS and may be involved in seizure generation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Our prospective study aimed at the validation of EpiTrack Junior, a neuropsychological screening tool for attention and executive functions in children with epilepsy., Methods: Twenty-two children with absence epilepsy aged 8-17 years underwent comprehensive neuropsychological evaluation including EpiTrack Junior and measures of intelligence, verbal and nonverbal memory, word fluency and visuoconstructive organization. Concurrent and discriminant validity of EpiTrack Junior subtests and total score as well as sensitivity and specificity of the total score were analyzed., Results: EpiTrack Junior total score was impaired in 59% of participants. Concurrent validity was demonstrated in 4/6 subtests and for the total score. Discriminant validity was shown with respect to verbal and nonverbal long-term memory. Sensitivity was higher than specificity and highest for the "working memory index"., Conclusion: EpiTrack Junior is recommended as a sensitive and time-efficient screening tool for attention and executive functions in children with epilepsy. Impaired results should be followed up with detailed evaluation including information from the parents and school as well as counseling where indicated., (© 2013.)

Although attention problems have often been described in children with childhood absence epilepsy (CAE), the use of different methodological approaches, neuropsychological tests, and heterogeneous experimental groups has prevented identification of the selective areas of attention deficit in this population. In this study, we investigated several components of attention in children with CAE using a unique computerized test battery for attention performance. Participants included 24 patients with CAE and 24 controls matched for age and sex. They were tested with a computerized test battery, which included the following tasks: selective attention, impulsivity, focused attention, divided attention, alertness, and vigilance. Compared with healthy controls, patients with CAE made more commission errors in the Go/No-Go task and more omission errors in the divided attention task. Childhood absence epilepsy patients also showed decreased reaction times in measures of selective attention and a great variability of reaction times in alertness and Go/No-Go tasks. Our findings suggest that patients with CAE were impaired in tonic and phasic alertness, divided attention, selective attention, and impulsivity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aripiprazole (APZ) is regarded as a first-line atypical antipsychotic used for the treatment of first and multiple episodes of schizophrenia to improve positive- and negative-symptoms. Its therapeutic indications were extended to acute manic and mixed episodes associated with bipolar disorder. In addition, APZ was approved as an adjunct therapy for major depressive disorder in 2007. Compared to other antipsychotic drugs, APZ has a unique pharmacological profile. It is a partial agonist at D₂ dopamine receptors and serotonin 5-HT(1A) and 5-HT₇ receptors, whereas it is an antagonist at serotonin 5-HT(2A) and 5-HT₆ receptors. Since epilepsy is often accompanied with neurological comorbidities such as depression, anxiety and cognitive deficits caused by both the disease and/or drug treatment, we wished to examine the effects of a sub-chronic treatment (>14 consecutive days) with APZ (0.3, 1 and 3 mg/kg; i.p.) on both absence seizures and WAG/Rij rat's behavior using different standard paradigms: Open field (OF) test, elevated plus maze (EPM) test, forced swimming (FS) test, sucrose consumption (SC) test and Morris water maze (MWM). WAG/Rij rats represent a validated genetic animal model of absence epilepsy with mild-depression comorbidity, also including other behavioral alterations. APZ treatment showed some anti-absence properties and regarding the behavioral comorbidity in this rat strain, we observed that APZ possesses clear antidepressant effects in the FS and SC tests also increasing memory/learning function in the Morris water maze test. In the two anxiety models used, APZ showed only minor effects. In conclusion, our results indicate that APZ might actually have a potential in treating absence seizures or as add-on therapy but more interestingly, these effect might be accompanied by positive modulatory actions on depression, anxiety and memory which might be also beneficial in other epileptic syndromes. This article is part of a Special Issue entitled 'Cognitive Enhancers'., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.)

A girl with intractable absence seizures and facial myoclonia at age 7 years was eventually diagnosed with hyperinsulinism-hyperammonemia syndrome because of hypoglycemia, hyperinsulinism, hyperammonemia, and the results of an oral l-leucine loading test. Her seizures occurred even during periods of relatively normal blood glucose levels, and were completely suppressed by diazoxide treatment only. Her diagnosis of hyperinsulinism-hyperammonemia syndrome was confirmed by a loss of sensitivity of glutamate dehydrogenase for guanosine 5'-triphosphate. Genetic studies identified the I444M mutation in the GLUD1 gene, which encodes glutamate dehydrogenase. This case illustrates the complex relationship between seizures and hypoglycemia in hyperinsulinism-hyperammonemia syndrome that can create diagnostic difficulties. The possibility of hyperinsulinism-hyperammonemia syndrome should be considered in patients with refractory absence seizures with myoclonia., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Atypical absence seizures are drug resistant in the majority of children with Lennox-Gastaut syndrome and herald a poor neurodevelopmental outcome. Here we studied the effects of environmental enrichment, enriched housing conditions designed to stimulate sensory and motor systems in the brain, on behavioral outcome in mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY), a clinically relevant model of atypical absence epilepsy. Beginning at postnatal day (P) 2, C3H mice were treated with AY (7.5 mg/kg) every 6 days until P20 and then weaned into enriched or standard cages. After 30 days (∼P50), AY mice from the enriched housing condition exhibited less behavioral hyperactivity and anxiety, improved olfactory recognition, and spatial learning, but no significant reduction in the number of ictal discharges in comparison with their non-enriched cohorts. The beneficial effects of environmental enrichment in AY model were in some behavioral tests gender-specific in favor of males suggesting that other, possibly hormonally mediated mechanisms, may interact with the therapeutic effects of enrichment. Taken together, these data provide a starting point to derive clinical occupational therapies for improving behavioral outcome in cases of intractable childhood seizures.

Hypoglycemia and hypoglycorrhachia, although they are uncommon causes of refractory seizures and epilepsy, should always be considered because they are potentially treatable conditions. A high index of suspicion and low threshold for testing recurrent blood and at least one cerebrospinal fluid glucose level are required. Jeavons syndrome and other refractory cryptogenic/idiopathic epilepsies may involve symptomatic etiologies, including hyperinsulinism, GLUT1 deficiency, and other metabolic disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We describe a 15-year-old boy with learning difficulties and eyelid myoclonia with absences (EMA). Myoclonic jerks of the extremities and trunk occurred 9 years before the onset of EMA, when the patient was 6. At that time, we diagnosed him with cryptogenic myoclonic epilepsy of early childhood, because he manifested mainly myoclonic jerks with generalized 3- to 6-Hz spike/polyspike-and-slow-wave complexes on EEG, normal neurological examination, good response to antiepileptic drugs, and no evidence of previous brain damage. This is an unusual case showing that myoclonic epilepsy of early childhood can evolve to EMA. Although the question of whether EMA is a seizure type or an epilepsy syndrome remains controversial, our case suggests that EMA is a seizure type during the clinical course of a particular kind of myoclonic epilepsy., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

l-2 hydroxyglutaric aciduria is a rare, autosomal recessively inherited metabolic disorder of organic acid metabolism. A 5-year-old boy presented with eyelid myoclonia with absences that proved difficult to control with first-line anticonvulsants. An electroencephalogram produced profoundly abnormal results, with generalized spike-and-wave discharges. The patient became seizure-free with a combination therapy of clonazepam, levetiracetam, and lamotrigine. Magnetic resonance imaging demonstrated subcortical white matter and basal ganglia alterations. Urinary organic acid analysis demonstrated increased excretion of l-2 hydroxyglutaric acid. Although rare, seizures can occur as a presenting sign of slowly progressing organic acidurias, e.g., l-2 hydroxyglutaric aciduria. Both eyelid myoclonia with absences and l-2 hydroxyglutaric aciduria comprise rare disorders. To our knowledge, this case report is the first of l-2 hydroxyglutaric aciduria presenting with symptomatic eyelid myoclonia with absences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

We report the case of a six-year-old female with childhood absence epilepsy who developed combined aPTT prolongation, not corrected by normal plasma, and atypical skin eruption six months after initiating lamotrigine treatment with dose increment. Two weeks after lamotrigine withdrawal, the skin eruption disappeared and aPTT normalised. To our knowledge, this is the first report of aPTT prolongation possibly due to factor inhibitors associated with lamotrigine monotherapy.

Early-onset absence epilepsy refers to patients with absence seizures beginning before age four and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a girl with intractable absence seizures with onset at age eight months. Her seizures were characterised by loss of responsiveness, with eyes drifting upwards and some myoclonic jerks of the upper and lower limbs. These symptoms were accompanied by bilaterally symmetric high-amplitude 2-2.5 Hz generalised spike-and-wave discharges on the electroencephalogram. Her seizures were refractory to conventional antiepileptic drugs; treatment with adrenocorticotropic hormone was transiently effective. Comprehensive metabolic screening, cytogenetic, and genetic analysis did not determine an underlying cause of her condition. Patients with intractable, very early-onset absence epilepsy with a myoclonic component have an unfavourable outcome and may be classified under a new epileptic syndrome, such as "early infantile absence epilepsy".

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.)

Reflex epilepsy is characterized by seizures that are precipitated by a specific identifiable factor. We describe here the case of a 21-year-old man with notable absence epilepsy since the age of 11 who experienced generalized convulsions 2 years after onset (in the absence of antiepileptic therapy) and reflex absence seizures triggered by walking 7-10 steps. To our knowledge, this case report is the first describing reflex absence epilepsy seizures induced by gait., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.)

Antiabsence drug ethosuximide (300 mg/kg/day in drinking water for 17 days) produced an antidepressant effect (a decrease in immobility time in forced swimming test) only in WAG/Rij rats genetically predisposed to absence epilepsy only at age of 5 months when spike-wave discharges well pronounced. On rats without spike-wave discharges (21-day-old WAG/Rij and Wistar rats at the age of both at 21 day and 5 months), ethosuximide didn't produce the antidepressant effect but tended to increases the immobility time and significantly decreases the number of divings (active behavior oriented to escape from stressful situation). Ethosuximide didn't substantially change the anxiety level in WAG/Rij rats but significantly enhanced anxiety in 21-day-old Wistar rats. The results suggest that ethosuximide is not possessed of antidepressant potential unrelated to its suppressive effect on spike-wave discharges.

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.)

This study sought to present clinical and outcome data of patients with idiopathic childhood occipital epilepsy of Gastaut, to validate previously reported characteristics of this epilepsy. The study group was comprised of 12 affected children (three boys and nine girls), with a median age of onset at 10.3 years. Common ictal manifestations included elementary visual hallucinations (75.0%), blindness or blurring of vision (50.0%), headache (50.0%), and secondarily generalized tonic-clonic seizures (58.3%). Interictal electroencephalography revealed occipital spike-wave paroxysms reactive to eye closure and opening in all patients, accompanied by spike-wave activity in the extra-occipital areas in four (33.3%), and by generalized spike-wave discharges in two (16.7%). One patient exhibited the onset of occipital lobe seizures 1 year after manifesting absence epilepsy. Seizure remission occurred in 81.8% of cases, in half of which medication was discontinued by late adolescence. This study confirmed the previously delineated electroclinical features of epilepsy syndrome, with additional aspects including the frequent association of generalized tonic-clonic seizures and atypical evolution from childhood absence epilepsy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Benign myoclonic epilepsy of infancy is a rare idiopathic generalized epileptic syndrome occurring below the age of 3 years. Although benign outcome is presumed, some recent studies suggest less favorable outcome. A 14-year-old boy had a history of repeated episodes of myoclonic jerks of the shoulders and upper limbs in infancy (age 5 months). An ictal electroencephalogram indicated generalized spike-wave discharges associated with the myoclonic seizures, and the diagnosis of benign myoclonic epilepsy of infancy was made. Valproate treatment resulted in control of the myoclonic seizures, and the drug was withdrawn when the patient was 5 years of age. At the age of 10, he presented with episodes of eyelid jerks associated with brief lapses in concentration triggered by sunlight. Electroencephalography revealed photosensitivity and a pattern of eye-closure sensitivity. These features were compatible with the diagnosis of eyelid myoclonia with absences, or Jeavons syndrome. Lamotrigine eliminated the seizures. The evolution of benign myoclonic epilepsy of infancy to eyelid myoclonia with absences has been reported in one other case. A possible continuum of myoclonic epileptic syndromes, mediated by a common genetic abnormality, suggests the need for longer monitoring of patients with benign myoclonic epilepsy of infancy., (Copyright 2010 Elsevier Inc. All rights reserved.)

The current study examined the specific types of attention-related problems children with childhood absence epilepsy (CAE) experience and the role of disease factors in the development of attention-related problems. Thirty-eight subjects with CAE and 46 healthy controls, aged 6 to 16, participated in the study. The Behavior Assessment System for Children (BASC) was completed by parents, and the Attention Problems and Hyperactivity subscales were used to characterize the problems of children with CAE. Item analysis within the subscales revealed that children with CAE demonstrate higher rates of hyperactive (overactivity and fidgetiness) and inattentive (forgetfulness and distractibility) problems, and require more supervision. Within-CAE-group analyses revealed that those who were actively having seizures were more impatient and those with a longer duration of illness were less proficient in completing homework. Children with CAE are at risk for certain inattentive and hyperactive problems, which can differ depending on duration of illness and active seizure status., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We report two monochorionic twins that progressively developed, between ages 5 and 10, a combination of episodic neurological disorders including paroxysmal exercise-induced dyskinesia, migraine without or with aura, absence seizures and writer's cramp. CSF/serum glucose ratio was moderately decreased in both patients. Mutational analysis of SLC2A1 gene identified a de novo heterozygous missense mutation in exon 4. This novel mutation has been previously showed to disrupt glucose transport in vitro. Both patients showed immediate and near-complete response to ketogenic diet. This clinical observation suggests that a high index of suspicion for GLUT1 deficiency syndrome is warranted in evaluating patients with multiple neurological paroxysmal events., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

The nature and extent of the neuropsychological difficulties associated with childhood absence epilepsy (CAE) remain unclear. Because aberrant thalamocortical rhythms have been implicated in the pathogenesis of CAE, it was hypothesized that children with CAE would show greater difficulties in neuropsychological domains that are thought to be subserved by basal ganglia-thalamocortical circuits. Multivariate analysis of variance was used to compare the neuropsychological functioning of 16 children with CAE with that of 14 children with type 1 diabetes mellitus and 15 healthy children. The CAE group did not perform differently from the other groups on measures of intellectual functioning, memory, academic achievement, fine motor speed, or processing speed. In contrast, significant differences were found in problem solving, letter fluency, complex motor control, attention/behavioral inhibition, and psychosocial functioning. These results suggest that children with CAE show difficulties in neuropsychological functions thought to be subserved by the same regions implicated in the pathogenesis of the disorder., (Copyright 2010 Elsevier Inc. 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.)

Cerebrovascular blood flow in absence seizures and flow patterns during the ictal period have not been thoroughly investigated. We aimed to evaluate cerebral blood flow changes in typical juvenile absence seizures during the ictal and postictal phases. Seizures were recorded in three patients (mean age: 21 +/- 1 years) with multiple daily typical absence seizures. Simultaneous video electroencephalography and bilateral middle cerebral artery transcranial Doppler ultrasonography recordings were conducted during seizures. Basal, ictal, and postictal blood flow velocities were recorded bilaterally, and offline analyses were performed in relation with generalized spike and wave discharges. Total of 43 seizures were recorded. Ictal increase and postictal decrease of cerebral blood flow velocities were significant for both sides (P < 0.001). The interhemispheric asymmetry in the ictal velocity increase was significant (P < 0.05). The interhemispheric asymmetry in the postictal velocity decrease was not significant (P > 0.05). The blood flow velocity increase after seizure onset indicates a vascular coupling mechanism. A sudden and then a gradual decrease in blood flow velocity, which lasted even after the seizure ceased, might suggest a preventive mechanism to avoid excessive seizure duration or even an absence status epilepticus. Significant asymmetries in increase and a symmetrical decrease may support the cortical focus theory.

About 40% of children with childhood absence epilepsy develop generalized tonic-clonic seizures. It is commonly held that polyspike-wave pattern on the electroencephalogram (EEG) can predict this development of generalized tonic-clonic seizures. However, there is no firm evidence in support of this proposition. To test this assumption, we used survival analysis and compared the incidence of generalized tonic-clonic seizures in 115 patients with childhood absence epilepsy having either isolated 3-Hz spike-wave or coexisting 3 Hz and polyspike-waves and other variables. There was no evidence that polyspike-waves predicted development of generalized tonic-clonic seizures in patients with childhood absence epilepsy. Later age of onset (> or =8 years) and family histories of generalized tonic-clonic seizures were the only independent predictors. These results have implications for counseling and in the choice of first-line antiepileptic drugs used for childhood absence epilepsy, especially if valproate is chosen based on the observation of polyspike-waves.

Paroxismal tonic upgaze of childhood (PTU) is a distinctive neuro-ophthalmological syndrome of unknown aetiology and pathogenesis that is characterized by episodes of sustained upward deviation of the eyes, often with incomplete downward saccades on attempted downgaze. Only few cases of PTU with co-existent epilepsy have been reported. We describe a case of female child affected by PTU who developed a childhood absence epilepsy (CAE) after 3 years from the beginning of disturbance. During hospitalization she presented repeated absence seizures; after the diagnosis of CAE, we started therapy with valproic acid (VPA). At the 6-month follow-up from the beginning of VPA therapy the child showed the disappearance of absence seizures with normalization of EEG, while no attenuation of PTU was observed. Our case suggests a possible association between PTU and epilepsy., (Copyright 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Few reports are available of ictal recordings in patients with benign focal epileptiform discharges. The study objective was to estimate the frequency of such recordings and to describe their clinical and electrophysiologic presentation. We performed a retrospective chart review of all patients undergoing routine electroencephalography (EEG) with video during a 10-year period. Among 214 patients with benign focal epileptiform discharges, 5 patients were identified with recorded EEG seizures (2.3%). Epilepsy syndromes included one case of benign focal epilepsy of childhood, three cases of childhood absence epilepsy, and in one case the patient presented with both. Only 1 of the 214 patients (0.4%) had a seizure characteristic of benign focal epilepsy of childhood. A literature review revealed the coexistence of childhood absence and benign focal epilepsy of childhood or benign focal epileptiform discharges within the same patient. These findings suggest that benign focal epilepsy of childhood seizures are rarely recorded during routine EEG, probably because seizures occur during the early morning part of the sleep cycle, which may differ from the brief nap during routine EEG. There was concurrence of generalized spike and wave discharges in these patients. It is unclear whether this is related to a common pathophysiologic factor.

Depression and/or anxiety are major comorbidities of epilepsy. However, the contribution of absence epileptic discharges in psychiatric syndromes is inconclusive. This study aimed to clarify the influence of absence seizure in anxiety- and depression-like behaviors using normal Wistar rats and Long-Evans rats with spontaneous spike-wave discharges (SWDs). Anxiety-like behaviors were evaluated by the open field (OF) and elevated plus maze (EPM) tests, and depression-like behaviors by the forced swimming (FS) and sucrose consumption (SC) tests. Long-Evans rats displayed significantly higher frequency and longer duration in the open arms of the EPM and in the center zone of the OF than did Wistar rats. Normalized behavioral indexes by movement also were significantly higher in Long-Evans rats. An excess of SWD numbers was associated with lower indexes and worse movement in the two behavioral tests. Ethosuximide eliminated the seizure frequency-dependent relationship and also significantly increased all indexes of the EPM test. Additionally, Long-Evans rats revealed significantly longer immobility in the FS test and lower consumption of sucrose solution in the SC test than did Wistar rats. Meanwhile, no relationship was found between immobility of the FS test and SWD number. Ethosuximide ameliorated depression-like behavior of Long-Evans rats that was equal to that of Wistar rats. Thus, Long-Evans rats showed seizure frequency-related exacerbation in anxiety-like behavior; and they displayed a depressive propensity. Our data suggest that generalized SWDs may have distinct influences in anxious and depressive behaviors.

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.

Absence seizures are one of the features of idiopathic generalised epilepsy (IGE) and occur as component of many different syndromes. They are commonly associated with various clinical features such as mild clonic components, change in postural tone, automatisms and autonomic phenomena. Childhood absence epilepsy (CAE) is the prototype IGE with typical absence seizures. We report a child who had prominent ictal hiccups during an absence seizure, and discuss the possible mechanisms. [Published with video sequences].

WAG/Rij rats given placebo showed a depression-like state as compared with normal Wistar rats (lacking convulsive pathology); this was analogous to the state previously seen in rats of this line, with decreased investigative activity in the open field test, increased immobility in the forced swimming test, and decreased consumption and preference for sucrose solution (anhedonia). Chronic administration of the tricyclic antidepressant imipramine (15 mg/kg, i.p., 15 days) had therapeutic (antidepressant) effects on depression-like behavior in WAG/Rij rats. After withdrawal of antidepressant therapy, the behavior of WAG/Rij rats was not significantly different from that of Wistar rats. Acute (single-dose) administration of the selective dopamine D2/D3 receptor antagonist raclopride (100 microg/kg, i.p., 15 min before the start of behavioral testing) increased the symptoms of depression-like behavior and suppressed the antidepressant effect of chronic administration of imipramine in WAG/Rij rats. Raclopride had no significant effect on behavior in Wistar rats. Administration of the dopamine D2/D3 receptor agonist parlodel (a therapeutic form of bromocriptine) cured the depression-like behavior of WAG/Rij rats and had no significant effect on behavior in Wistar rats, with the exception of a reduction in the duration of immobility in the forced swimming test. Imipramine and raclopride had no significant effect on the levels of total movement activity and anxiety in either WAG/Rij or Wistar rats. These results demonstrate the dopamine-dependent nature of depression-like behavior in WAG/Rij rats and show the possible involvement of dopamine D2 receptors in mediating the antidepressant effect of imipramine on genetically determined depression-like behavior in WAG/Rij rats.

Both genetic and acquired factors play important roles in the development of childhood absence epilepsy. This article describes a girl with mental retardation, probably due to a perinatal complication, who had typical absence seizures with characteristic electroencephalographic findings of childhood absence epilepsy, including normal background activity. This patient was subsequently found to have a strong genetic predisposition, which was suggested by the fact that childhood absence epilepsy also developed in her younger brother. Except for the mental subnormality, the electroclinical features of this patient satisfied the diagnostic criteria for childhood absence epilepsy. This case raises the question about diagnostic consideration of childhood absence epilepsy in association with cerebral pathology for genetically predisposed individuals.

Purpose: An attempt to allocate patients with the clinical features and electroencephalography (EEG) abnormalities of typical absence epilepsy presenting before the age of 3 years, similar to childhood and juvenile absence epilepsy (JAE) and delineate the clinical manifestations, EEG abnormalities, therapy and outcome of such an epileptic disorder by conducting a nationwide survey., Results: Overall, eight infants, six males and two females, abided by the inclusion criteria of typical absence epilepsy: They were born after an unremarkable pregnancy and labor presenting at the age of 12-34 months (mean: 19.6 months) with frequent absences time-linked with an EEG demonstrating generalized occasionally irregular epileptiform discharges of 3-4 Hz spike/wave and normal background activity along with an electrographic photosensitive response in one patient. Neurological examination was intact in all infants. All eight infants were initially treated with valproic acid, of whom seven immediately responded and one had increase in frequency and duration of absences completely aborted with treatment of lamotrigine. Three relapsed after termination of therapy of whom two again presented with recurrent absences and another one with generalized tonic-clonic seizures and as such these children had virtually transformed into a later form of idiopathic generalized epilepsy (IGE) during childhood. All eight patients are seizure-free, seven still on therapy; seven children within a follow-up period of 2-7 years and the most recently diagnosed infant for 6 months. Cognitive skills were found normal in all children within the low normal range in three children with short attention and concentration spans., Conclusion: The data presented here delineate a very rare form of idiopathic benign generalized epilepsy presenting with typical absences before age of 3 years and a favorable outcome, similar to childhood and JAE, recognized as distinct IGE syndromes by the International League Against Epilepsy (ILAE) classification.

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.

Eyelid myoclonia is a type of epileptic seizure characterized by marked jerking of the eyelids, often associated with jerky upward deviation of the eyeballs. It can be triggered by eye closure. The ictal electroencephalographic pattern of eyelid myoclonia consists of generalized polyspike waves at 3 to 6 Hz. Eyelid myoclonia can be a component of the clinical seizures seen with idiopathic, symptomatic, or cryptogenic generalized epilepsy. The objective of this study was to describe the unusual focal ictal electroencephalogram features of two patients with developmental delay and eyelid myoclonia. To the best of our knowledge, this unique electroencephalogram finding was not previously described.

Pharmacological inhibition and high-frequency stimulation (HFS) of the substantia nigra pars reticulata (SNr) suppress seizures in different animal models of epilepsy. The aim of the present study was to determine the optimal parameters of HFS to control spontaneous seizures in a genetic model of absence epilepsy in the rat. Single SNr stimulation that was bilateral, bipolar and monophasic at 60 Hz frequency and with 60-micros pulse width was optimal. However, when used for repeated stimulations, long-term suppression did not occur and even the number of seizures increased. A delay of at least 60 s between stimulations was necessary to be fully effective. Although single HFS of the SNr can be used to suppress ongoing seizures, repeated HFS is ineffective and could even aggravate seizures in our model. Thus investigations of accurate stimulation procedures are still needed.