Common Epilepsy Syndrome Research Articles

Seizure outcomes after resective surgery for extra–temporal lobe epilepsy in pediatric patients

While temporal lobe epilepsy (TLE) is the most common epilepsy syndrome in adults, seizures in children are more often extratemporal in origin. Extra-temporal lobe epilepsy (ETLE) in pediatric patients is often medically refractory, leading to significantly diminished quality of life. Seizure outcomes after resective surgery for pediatric ETLE vary tremendously in the literature, given diverse patient and epilepsy characteristics and small sample sizes. The authors performed a systematic review and meta-analysis of studies including 10 or more pediatric patients (age ≤ 19 years) published over the last 20 years examining seizure outcomes after resective surgery for ETLE, excluding hemispherectomy. Thirty-six studies were examined. These 36 studies included 1259 pediatric patients who underwent resective surgery for ETLE. Seizure freedom (Engel Class I outcome) was achieved in 704 (56%) of these 1259 patients postoperatively, and 555 patients (44%) continued to have seizures (Engel Class II-IV outcome). Shorter epilepsy duration (≤ 7 years, the median value in this study) was more predictive of seizure freedom than longer (> 7 years) seizure history (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.07-2.14), suggesting that earlier intervention may be beneficial. Also, lesional epilepsy was associated with better seizure outcomes than nonlesional epilepsy (OR 1.34, 95% CI 1.19-1.49). Other predictors of seizure freedom included an absence of generalized seizures (OR 1.61, 95% CI 1.18-2.35) and localizing ictal electroencephalographic findings (OR 1.55, 95% CI 1.24-1.93). In conclusion, seizure outcomes after resective surgery for pediatric ETLE are less favorable than those associated with temporal lobectomy, but seizure freedom may be more common with earlier intervention and lesional epilepsy etiology. Children with continued debilitating seizures despite failure of multiple medication trials should be referred to a comprehensive pediatric epilepsy center for further medical and surgical evaluation.

A neurodevelopmental basis for BECTS: Evidence from structural MRI

BECTS (benign epilepsy with centro-temporal spikes) is one of the most common childhood-onset epilepsy syndromes. We investigated quantitative evidence for brain morphological variation associated with BECTS to provide insights into the neuroanatomical basis of this disorder. Three independent BECTS groups were imaged at different stages: (a) near onset (n=16, mean age 9.3±1.6 years), (b) ~9 years after onset (n=9, mean age 15.8±2.3 years), and (c) ~15 years after onset (n=10, mean age 22.7±2.7 years). Age-matched controls were imaged with each group. Whole brain T1-weighted MRI was acquired. Voxel-based morphometry (groups a-c) and cortical thickness analyses (groups b and c) were undertaken within each group and for the groups combined. The relationship between cortical morphology and age was investigated. The voxel-based morphometry analysis indicated increased bilateral grey matter volume in the superior frontal gyrus, insula and right inferior frontal gyrus regions in BECTS. The magnitude of the increase lessened with age of the cases. Cortical thickness analysis revealed thicker cortex in BECTS along middle and inferior frontal gyri bilaterally, left insula and bilateral supramarginal gyrus in the 9-year-after-onset group, that normalised with age. The rate of cortical thickness changes with age were greater in BECTS cases than in controls. Increased cortical gray matter associated with BECTS was found. The decreasing magnitude of the effect with increasing age parallels the natural history of the disorder. The areas affected are consistent with neurocognitive dysfunction in BECTS.

Frontal lobe function and structure in juvenile myoclonic epilepsy: A comprehensive review of neuropsychological and imaging data

Juvenile myoclonic epilepsy is the most common idiopathic epilepsy syndrome and is considered a benign seizure disorder that responds well to antiepileptic drug treatment, in particular sodium valproate. By definition, routine brain imaging shows no abnormalities, but advanced imaging studies have identified functional and structural abnormalities in the frontal cortex and thalamus. Neuropsychological studies revealed subtle cognitive deficits in patients with JME, mainly implicating the frontal lobes. These findings are in keeping with anecdotal reports of behavioral problems in JME. Cognitive dysfunction in otherwise healthy siblings of patients with JME and a high heritability support the concept of a genetically determined thalamo-frontocortical network dysfunction, accounting for the cognitive impairment and cognitively triggered "motor seizures."

Neuroimaging in the definition and organization of the epilepsies: We’re not there yet

Neuroimaging significantly affects the diagnosis and treatment of patients with patients. Despite its importance, magnetic resonance imaging (MRI) has been marginally incorporated into concepts used to define epilepsy etiologies by the International League Against Epilepsy (ILAE) Classification Commission. We propose that Structural etiology be defined as positive neuroimaging abnormalities likely causing the seizures. This would contrast with Genetic and Unknown etiologies, where imaging shows no overt structural abnormality that explains the seizures. It is further recommended that Structural and Metabolic be separated into individual categories, as the outcomes and therapies are different. It is advocated that Structural etiology be subdivided into subgroups based on MRI and surgical syndromes. With this approach, the ILAE should acknowledge that both MRI and electroencephalography (EEG) are necessary diagnostic tools in the classification of epilepsy syndromes and etiologies in the modern era. Promoting the use of neuroimaging into concepts that determine terminology will promote the notion that epilepsy classification should consider structural etiology of the seizures, along with the frequency of the most common epilepsy syndromes, and prognosis for spontaneous and treated remission and cure.

Striatal hypertrophy and its cognitive effects in new‐onset benign epilepsy with centrotemporal spikes

Benign epilepsy with centrotemporal spikes (BECTS), the most common childhood epilepsy syndrome, is a neurodevelopmental disorder with a genetic influence. Despite its signature electroencephalographic pattern and distinct focal motor seizure semiology, little is known about the underlying brain anatomic alteration and the corresponding cognitive consequences. Given the motor manifestations of seizures in BECTS, we hypothesize that anatomic networks in BECTS involve a distributed corticostriatal circuit. We investigated volumetric differences and shape deformities of caudate, putamen, pallidum, and thalamus in a group of children with new- and recent-onset BECTS (N = 3) compared to healthy controls (N = 54). We correlated specific subcortical volumes in BECTS that were significantly different from those in healthy controls with performances in executive function. Children with BECTS demonstrated significantly hypertrophied putamen, which was selective among the subcortical regions examined. Shape analysis showed dorsoventral elongation of the left caudate and bilateral putamen, with subnuclei expansion in ventral and dorsal striatum. Larger putamen volumes were linked to better cognitive performances on two complementary executive function tests. Children with BECTS showed aberrant volume and shape in subcortical regions that are critical for both motor processing and executive function. It is of importance to note that the hypertrophy appears to be cognitively adaptive, as enlargement was associated with improved cognitive performances. The anatomic abnormalities and their cognitive effects are evident in a group of children with new- and recent-onset epilepsy, suggesting that the structural brain anomalies occurred before the diagnosis of epilepsy.

Lamotrigine and side effects

For approximately 65 million people in the world with epilepsy, antiepileptic drugs (AEDs) are the mainstay of treatment.1 Lamotrigine (LTG) is a nonenzyme inducing AED with favorable pharmacokinetics, approved for use by the Food and Drug Administration (FDA) in epilepsy as well as bipolar disorder. From May 2009 to April 2010, approximately 9 million prescriptions were dispensed from outpatient pharmacies.2 In epilepsy, it has proven to be effective in a wide variety of seizure types and patient groups (2 years of age and older), with clinical applicability in focal seizures and in generalized seizures associated with both genetic epilepsy and the Lennox-Gastaut syndrome. Both the efficacy and safety profile of LTG have been defined by numerous clinical studies.3 Compared with other first-line AEDs, LTG is well tolerated with little sedation or cognitive impairment, weight neutrality, and a favorable psychotropic profile. A recent large randomized comparative effectiveness trial found LTG as the drug of first choice for patients with presumed partial (focal) epilepsy.4 Since efficacy among AEDs does not differ for common epilepsy syndromes, tolerability becomes a critical factor in drug selection.3 Adverse effects have long been recognized with all AEDs.5 Upon its release in 1994, rash hampered the use of LTG. A black box warning in the prescribing information reflected the possibility of serious rash …

Prolonged increase in rat hippocampal chemokine signalling after status epilepticus

Temporal lobe epilepsy (TLE) is one of the most common focal epilepsy syndromes. In a genome-wide expression study of the human TLE hippocampus we previously showed up-regulation of genes involved in chemokine signalling. Here we investigate in the rat pilocarpine model for TLE, whether changes in chemokine signalling occur during epileptogenesis and are persistent. Therefore we analysed hippocampal protein expression and cellular localisation of CCL2, CCL4, CCR1 and CCR5 after status epilepticus. We found increased CCL4 (but not CCL2) expression in specific populations of hilar astrocytes at 2 and 19weeks after SE concomitant with a persistent up-regulation of its receptor CCR5. Our results show an early and persistent up-regulation of CCL4/CCR5 signalling during epileptogenesis and suggest that CCL4 signalling, rather than CCL2 signalling, could have a role in the epileptogenic process.

Rates and predictors of long-term seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta-analysis

Frontal lobe epilepsy (FLE) is the second-most common focal epilepsy syndrome, and seizures are medically refractory in many patients. Although various studies have examined rates and predictors of seizure freedom after resection for FLE, there is significant variability in their results due to patient diversity, and inadequate follow-up may lead to an overestimation of long-term seizure freedom. In this paper the authors report a systematic review and meta-analysis of long-term seizure outcomes and predictors of response after resection for intractable FLE. Only studies of at least 10 patients examining seizure freedom after FLE surgery with postoperative follow-up duration of at least 48 months were included. Across 1199 patients in 21 studies, the overall rate of postoperative seizure freedom (Engel Class I outcome) was 45.1%. No trend in seizure outcomes across all studies was observed over time. Significant predictors of long-term seizure freedom included lesional epilepsy origin (relative risk [RR] 1.67, 95% CI 1.36-28.6), abnormal preoperative MRI (RR 1.64, 95% CI 1.32-2.08), and localized frontal resection versus more extensive lobectomy with or without an extrafrontal component (RR 1.71, 95% CI 1.26-2.43). Within lesional FLE cases, gross-total resection led to significantly improved outcome versus subtotal lesionectomy (RR 1.99, 95% CI 1.47-2.84). These findings suggest that FLE patients with a focal and identifiable lesion are more likely to achieve seizure freedom than those with a more poorly defined epileptic focus. While seizure freedom can be achieved in the surgical treatment of medically refractory FLE, these findings illustrate the compelling need for improved noninvasive and invasive localization techniques in FLE.

A novel SCN1A missense mutation causes generalized epilepsy with febrile seizures plus in a Chinese family

Generalized epilepsy with febrile seizures plus (GEFS+) is a common familial epilepsy syndrome, which generally develops in childhood. GEFS+ is caused by mutations in the sodium-channel α1-subunit (SCN1A). In this report, we investigated a Chinese family with an autosomal dominant form of GEFS+. The affected GEFS+ patients in this family displayed significant inter-family clinical heterogeneity. Linkage analysis localized the disease-causing gene to chromosome 2q24, where SCN1A is located. Furthermore, DNA sequencing of the whole coding region of SCN1A revealed a novel heterozygous nucleotide substitution (c.577C>T) causing a missense mutation (p.L193F) in the S3 segment of SCN1A domain D1. Our results expand the spectrum of SCN1A mutations and provide novel insights between the SCN1A mutations and the clinical variations of GEFS+.

Coexistence of idiopathic generalized epilepsy among surgically treated patients with drug-resistant temporal lobe epilepsy

Failure to identify the association antiepileptic drug (AED)-resistant temporal lobe epilepsy (TLE) with idiopathic generalized epilepsy (IGE) can interfere with decision for anterior temporal lobectomy (ATL) and prediction of post-ATL seizure outcome. Out of the 664 consecutive patients who underwent ATL between March 1995 and December 2007, 12 (1.8%) had coexisting IGE. The decision for ATL was made after a thorough discussion in the multidisciplinary patient management conference based upon the concordance between the clinical, electroencephalographic and magnetic resonance imaging data. All of them underwent epilepsy surgery for AED-resistant TLE. In seven of the 12 patients, IGE was not identified until post-ATL. During a median follow-up period of 8.5 years, 8 of our 12 patients were seizure-free; the remaining 4 patients only had infrequent myoclonus. In two them, AEDs were discontinued; others were on montherapy for IGE. Our study highlights the rare association of IGE with TLE, the most common AED-resistant focal epilepsy syndrome. As the seizure outcome following ATL is similar in AED-resistant TLE patients with and without IGE, their co-existence is not a contraindication for ATL. Future studies should explore the molecular genetic basis of the rare association between these two epilepsy syndromes.

The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis

Temporal lobe epilepsy, one of the most common epilepsy syndromes, is characterized by hippocampal hyperexcitability and progressive seizure susceptibility. Omega-3 fatty acids are involved in neuronal excitability and have anticonvulsant properties. We studied the effect of docosahexaenoic acid (DHA) or its derived lipid mediator, neuroprotectin D1 (NPD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid), in evoked seizures using a rapid kindling model of temporal lobe epilepsy. DHA or NPD1 was administered in rodents with or without kindling acquisition. Locomotor seizures and evoked epileptiform hippocampal activity immediately after hippocampal stimulations were analyzed. DHA or NPD1 limits hippocampal electrically induced hyperexcitability. Seizures induced by kindling triggered NPD1 synthesis in the hippocampus. Supplying its precursor, DHA, or direct injection of NPD1 into the third ventricle resulted in attenuation of kindling progression and hippocampal hyperexcitability. The significance of NPD1 in temporal lobe epilepsy could open new pathways for understanding the initiation and propagation of seizures and the role this lipid mediator plays in the neuronal network.

Increase in BDNF-mediated TrkB signaling promotes epileptogenesis in a mouse model of mesial temporal lobe epilepsy

Mesio-temporal lobe epilepsy (MTLE), the most common drug-resistant epilepsy syndrome, is characterized by the recurrence of spontaneous focal seizures after a latent period that follows, in most patients, an initial insult during early childhood. Many of the mechanisms that have been associated with the pathophysiology of MTLE are known to be regulated by brain-derived neurotrophic factor (BDNF) in the healthy brain and an excess of this neurotrophin could therefore play a critical role in MTLE development. However, such a function remains controversial as other studies revealed that BDNF could, on the contrary, exert protective effects regarding epilepsy development. In the present study, we further addressed the role of increased BDNF/TrkB signaling on the progressive development of hippocampal seizures in the mouse model of MTLE obtained by intrahippocampal injection of kainate. We show that hippocampal seizures progressively developed in the injected hippocampus during the first two weeks following kainate treatment, within the same time-frame as a long-lasting and significant increase of BDNF expression in dentate granule cells. To determine whether such a BDNF increase could influence hippocampal epileptogenesis via its TrkB receptors, we examined the consequences of (i) increased or (ii) decreased TrkB signaling on epileptogenesis, in transgenic mice overexpressing the (i) TrkB full-length or (ii) truncated TrkB-T1 receptors of BDNF. Epileptogenesis was significantly facilitated in mice with increased TrkB signaling but delayed in mutants with reduced TrkB signaling. In contrast, TrkB signaling did not influence granule cell dispersion, an important feature of this mouse model which is also observed in most MTLE patients. These results suggest that an increase in TrkB signaling, mediated by a long-lasting BDNF overexpression in the hippocampus, promotes epileptogenesis in MTLE.

PEDIATRIC EPILEPSY SYNDROMES

Epilepsy syndromes denote specific constellations of clinical seizure type(s), EEG findings, and other characteristic clinical features. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years. Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology that is known or presumed based on other evidence of brain dysfunction. Epilepsies are also classified by those with generalized seizures and those with localization-related seizures. Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome for children with epilepsy. In this chapter, clinical and electrographic features as well as inheritance patterns of common pediatric epilepsy syndromes are discussed.

Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy

Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined. In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons. The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03). Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)

Juvenile myoclonic epilepsy, a common epilepsy syndrome

In their article “Juvenile myoclonic epilepsy 25 years after seizure onset: A population-based study” (Neurology 2009;73:1041–1045), Drs. Camfield and Camfield studied something that has never been evaluated: how a group of people with this kind of epilepsy do over a long period of time. On the surface, it seems that it would be easy to identify a group of people, follow them for a long time, and then describe what happened to them. However, in our modern world, where people move frequently and sometimes over long distances, long-term studies can be very hard—if not impossible—to do. Working in Nova Scotia, Drs. Camfield and Camfield identified people with JME. They looked carefully at their medical records to be certain that the group did not have another kind of epilepsy. For instance, the people could have had a generalized tonic-clonic seizure, but mainly were experiencing myoclonic seizures. Medical testing, such as an electroencephalogram (EEG), had to show the kind of abnormality that occurs in this kind of epilepsy (called a 3-hertz spike-and-wave pattern). Of course, the history, such as the age at onset, and a possible family history of epilepsy was carefully reviewed. After all of these conditions were met, Drs. Camfield and Camfield had identified 24 people with JME. To find this group, the doctors reviewed the medical records of anyone who had been diagnosed with epilepsy between 1977 and 1985. Remember, they wanted to see how these people were going to do over 25 years, so they had to look back to the 1970s and 1980s to find people who would have had epilepsy for that period of time. They narrowed the group to only those with JME, using the criteria above. All of the case files were reassessed between 2007 and 2008. The doctors also called the 24 people …

Neuropsychological and functional MRI studies provide converging evidence of anterior language dysfunction in BECTS

Benign childhood epilepsy with centrotemporal spikes (BECTS) is the most common epilepsy syndrome of childhood and can be associated with language difficulties. The exact profile of these difficulties and their neurofunctional underpinnings, however, are not yet clear. To further understand the impact of the BECTS syndrome on language, we assessed language performance using standard neuropsychological measures, and patterns of language lateralization using functional magnetic resonance imaging (fMRI) in children with typical BECTS (n = 20) and healthy controls (n = 20). The fMRI analyses revealed that language-related activation was less lateralized to the left hemisphere in anterior brain regions in the patients relative to the control group. This finding was consistent with decreased performance in the BECTS group compared to the control group on the neuropsychological measure most dependent on the integrity of anterior aspects of the language axis, namely, sentence production. The converging lines of evidence from the neuropsychological and activation methodologies support the view that BECTS is associated with language difficulties that are regional, and anterior, in nature.

Kognitive Defizite bei Kindern mit benigner Epilepsie des Kindesalters mit zentrotemporalen Spitzen

Die Rolando-Epilepsie stellt das häufigste Epilepsiesyndrom im Kindesalter dar. Kognitive Defizite treten vor allem in den Bereichen Sprache, Aufmerksamkeit, Gedächtnis, Exekutivfunktionen, Motorik und den visuokonstruktiven Leistungen häufig auf. Vor allem die sprachlichen Leistungen und damit zusammenhängende spezifische Bereiche wie das dichotische Hören und auditorische (Dys-)Funktionen stehen im Mittelpunkt der aktuellen Forschung. Das Review stellt differenziert die zugehörigen Befunde dar, auch im Hinblick auf möglicherweise persistierende Störungen nach einer vollständigen Remission der Epilepsie. Die Rolando-Epilepsie tritt im Grundschulalter auf und kann so die schulischen Leistungen negativ beeinflussen. Ansätze einer möglichst frühen kognitiven Förderung dieser Kinder sind vor allem im Hinblick auf schulische Anforderungen notwendig.

Treatment of seizures in childhood

The field of pediatric epilepsy is a rewarding yet challenging area of medicine. A fairly significant proportion of children remain refractory to current antiepileptic drugs, and may require alternative treatment options. Challenges also arise because many of the antiepileptic drugs available for use since 1993 are US FDA approved only for use over the age of 2–4 years, hence presenting a medicolegal conundrum to the treating physician. However, their more favorable side-effect profile and tolerability have led to their widespread use even in those less than 2 years of age. This review briefly outlines their indications, pharmacokinetic profile and dosages, and covers evidence-based guidelines for therapy in common epilepsy syndromes of childhood.

Human herpes virus 6B: A possible role in epilepsy?

Human herpes virus 6 (HHV6) infection is nearly ubiquitous in childhood and may include central nervous system invasion. There are two variants, HHV6A and HHV6B. Usually asymptomatic, it is associated with the common, self-limited childhood illness roseola infantum and rarely with more severe syndromes. In patients with immune compromise, subsequent reactivation of viral activity may lead to severe limbic encephalitis. HHV6 has been identified as a possible etiologic agent in multiple sclerosis, myocarditis, and encephalitis. A preponderance of evidence supports an association between HHV6 and febrile seizures. An ongoing multicenter study is investigating possible links between HHV6 infection, febrile status epilepticus, and development of mesial temporal sclerosis (MTS). Investigation of temporal lobectomy specimens showed evidence of active HHV6B but not HHV6A replication in hippocampal astrocytes in about two-thirds of patients with MTS but not other causes of epilepsy. It has been suggested that HHV6B may cause "excitotoxicity" by interfering with astrocyte excitatory amino acid transport. Although conventional inflammatory changes are not found in most MTS specimens, inflammatory modulators may play a role in neuronal injury leading to MTS as well. If the link between early viral infection, complex or prolonged febrile seizures, and later development of intractable temporal lobe epilepsy is confirmed, new therapeutic approaches to a common intractable epilepsy syndrome may be possible.

KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes

To explore the involvement of M-type potassium channels KCNQ2, Q3, and Q5 in the pathogenesis of common idiopathic epilepsies. Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case-control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls. An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004). Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.