Idiopathic Generalized Epilepsy Syndromes Research Articles

Generalized spike-waves in idiopathic generalized epilepsies: Does their frequency matter?

We hypothesized that the frequency (in Hertz) of generalized spike-waves (GSWs) in patients with idiopathic generalized epilepsy (IGE) has associations with the syndromic diagnosis as well as with the prognosis of patients (their response to medical treatment). This was a retrospective study of a prospectively developed database. All patients with a diagnosis of IGE were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. Patients were classified into four IGE syndromes: childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and generalized tonic-clonic seizures alone. Five hundred and eighty-three patients were studied. GSWs were commonly observed in all four syndromes of IGE. Frequency of GSW (in Hertz) did not have a significant association with the syndromic diagnosis of the patients (p=.179). The presence of GSW did not have a significant association with the seizure outcome (becoming seizure free or not) of the patients (p=.416). Frequency of GSW did not have a significant association with the seizure outcome of the patients either (p=.574). GSWs are the hallmark electroencephalographic footprints of idiopathic generalized epilepsies; however, neither their presence nor their frequency has practical associations with the syndromic diagnosis of IGEs or their outcome (response to treatment).

Resting-state electroencephalography microstates as a marker of photosensitivity in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy is an idiopathic generalized epilepsy syndrome associated with photosensitivity in approximately 30-40% of cases. Microstates consist of a brief period of time during which the topography of the whole resting-state electroencephalography signal is characterized by a specific configuration. Previous neurophysiological and neuroimaging studies have suggested that Microstate B may represent activity within the visual network. In this case-control study, we aimed to investigate whether anatomical and functional alterations in the visual network observed in individuals with photosensitivity could lead to changes in Microstate B dynamics in photosensitive patients with juvenile myoclonic epilepsy. Resting-state electroencephalography microstate analysis was performed on 28 patients with juvenile myoclonic epilepsy. Of these, 15 patients exhibited photosensitivity, while the remaining 13 served as non-photosensitive controls. The two groups were carefully matched in terms of age, sex, seizure control and anti-seizure medications. Multivariate analysis of variance and repeated-measures analysis of variance were performed to assess significant differences in microstate metrics and syntax between the photosensitive and the non-photosensitive group. Post hoc false discovery rate adjusted unpaired t-tests were used to determine differences in specific microstate classes between the two groups. The four classical microstates (Classes A, B, C and D) accounted for 72.8% of the total electroencephalography signal variance in the photosensitive group and 75.64% in the non-photosensitive group. Multivariate analysis of variance revealed a statistically significant class-group interaction on microstate temporal metrics (P = 0.021). False discovery rate adjusted univariate analyses of variance indicated a significant class-group interaction for both mean occurrence (P = 0.002) and coverage (P = 0.03), but not for mean duration (P = 0.14). Post hoc false discovery rate adjusted unpaired t-tests showed significantly higher coverage (P = 0.02) and occurrence (P = 0.04) of Microstate B in photosensitive patients compared with non-photosensitive participants, along with an increased probability of transitioning from Microstates C (P = 0.04) and D (P = 0.02) to Microstate B. No significant differences were found concerning the other microstate classes between the two groups. Our study provides novel insights on resting-state electroencephalography microstate dynamics underlying photosensitivity in patients with juvenile myoclonic epilepsy. The increased representation of Microstate B in these patients might reflect the resting-state overactivation of the visual system underlying photosensitivity. Further research is warranted to investigate microstate dynamics in other photosensitive epilepsy syndromes.

Coexistence of temporal lobe epilepsy and idiopathic generalized epilepsy

ObjectiveWe investigated the frequency of coexistence of temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) in a retrospective database study. We also explored the underlying pathomechanisms of the coexistence of TLE and IGE based on the available information, using bioinformatics tools. MethodsThe first phase of the investigation was a retrospective study. All patients with an electro-clinical diagnosis of epilepsy were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2023. In the second phase, we searched the following databases for genetic variations (epilepsy-associated genetic polymorphisms) that are associated with TLE or syndromes of IGE: DisGeNET, genome-wide association study (GWAS) Catalog, epilepsy genetic association database (epiGAD), and UniProt. We also did a separate literature search using PubMed. ResultsIn total, 3760 patients with epilepsy were registered at our clinic; four patients with definitely mixed TLE and IGE were identified; 0.1% of all epilepsies. We could identify that rs1883415 of ALDH5A1, rs137852779 of EFHC1, rs211037 of GABRG2, rs1130183 of KCNJ10, and rs1045642 of ABCB1 genes are shared between TLE and syndromes of IGE. ConclusionWhile coexistence of TLE and IGE is a rare phenomenon, this could be explained by shared genetic variations.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Differences in the distribution of triggers among resting state networks in patients with juvenile myoclonic epilepsy explained by network analysis.

Juvenile myoclonus epilepsy (JME) is an idiopathic generalized epilepsy syndrome. Functional connectivity studies based on graph theory have demonstrated changes in functional connectivity among different brain regions in patients with JME and healthy controls. However, previous studies have not been able to clarify why visual stimulation or increased cognitive load induces epilepsy symptoms in only some patients with JME. This study constructed a small-world network for the visualization of functional connectivity of brain regions in patients with JME, based on system mapping. We used the node reduction method repeatedly to identify the core nodes of the resting brain network of patients with JME. Thereafter, a functional connectivity network of the core brain regions in patients with JME was established, and it was analyzed manually with white matter tracks restriction to explain the differences in symptom distribution in patients with JME. Patients with JME had 21 different functional connections in their resting state, and no significant differences in their distribution were noted. The thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal lobe were the core brain regions that comprised the functional connectivity network in patients with JME during their resting state. The betweenness centrality of the prefrontal lobe and the visual cortex in the core functional connectivity network of patients with JME was lower than that of the other brain regions. The functional connectivity and node importance of brain regions of patients with JME changed dynamically in the resting state. Abnormal discharges originating from the thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal cortex are most likely to lead to seizures in patients with JME. Further, the low average value of betweenness centrality of the prefrontal and visual cortices explains why visual stimulation or increased cognitive load can induce epileptic symptoms in only some patients with JME.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy

After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Levetiracetam or lamotrigine as initial monotherapy. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

Idiopathic generalized epilepsies: Which seizure type is more difficult to control?

ObjectivesThe purpose of the current study was to investigate that which seizure type is more difficult to be brought under control with antiseizure medication treatment in patients with idiopathic generalized epilepsy (IGE). MethodsThis was a retrospective study of a large database of patients with epilepsy, which was built over more than a decade. All patients with a diagnosis of IGE, with at least 12 months of follow-up at our center, were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. Results358 patients were included. The seizure types were generalized tonic-clonic seizures (GTCSs) (in 87.2%), myoclonic seizures (in 57.5%), and absence seizures (in 51.7%). Among patients who had GTCSs (N = 312), 160 patients (51.3%) became free of this seizure type. Among patients who had myoclonic seizures (N = 206), 122 patients (59.2%) became seizure-free. Among patients who had absences (N = 185), 127 patients (68.6%) became seizure-free. The difference between the groups was significant (p = 0.0007). Receiving valproate was significantly associated with a myoclonus-free status (compared with other drugs). SignificanceThe likelihood of achieving seizure control is different for various seizure types in patients with IGE (achievement of seizure control is less likely for GTCSs and more likely for absences). Antiseizure drug efficacy should be considered along with other variables (e.g., sex) when selecting an ASM for a patient with IGE. Specifically designed clinical trials are needed to develop more efficacious and safe drugs to treat various syndromes of IGE.

Incidence and Associated Factors of Juvenile Myoclonic Epilepsy among Idiopathic Generalized Epilepsy

Juvenile myoclonic epilepsy (JME) is widely recognized presumed genetic, electroclinical idiopathic generalized epilepsy (IGE) syndrome. The prevalence of JME is about 18% of IGEs. However, there is a considerable variation in different settings.Aims: to determine the incidence and associated factors of JME among patients with IGEs.Patients and Methods: This retrospective study included a total of 52 patients with electro-clinical feature of IGE. All enrolled patients were undergone a three-hour video electroencephalography (EEG). JME was diagnosed on the basis of JME consensus definition clinical criteria class II. The demographic and clinical characteristics of the patients were abstracted from their records.Results: The most common epilepsy syndrome of IGE was generalized tonic-clonic seizure (GTCS) only affecting (32.7%) followed by juvenile absence epilepsy (JAE) (25%), JME and JME only (each 17.3%) and Generalized myoclonic epilepsy and generalized tonic-clonic (GMEGTC) (13.46%). All JME patients were females (100%) compared with 69.77% of the patients in other IGE syndromes with a highly significant difference. According to EEG results, 8 patients (88.89%) of JME patients had generalized polyspikes, and two patient (22.22%) showed generalized spikes and waves (3/second spike and wave complex). One patient (11.11%) two EEG findings (polyspike and generalized spike and waves)Conclusions: JME can affect adolescents and young adults and it can effect child age group. It is distinguished by the occurrence of myoclonic seizures, characteristic spike-and-wave EEG pattern at 4-6 Hz, and more common in females than males.

Classification and definition of epilepsy. Position paper by the International League Against Epilepsy on Nosology and Definitions of Epilepsy Syndromes dated 2021

This article presents updated and revised diagnostic criteria for epilepsy syndromes proposed in 2021 by the Nosology and Definitions Taskforce of the International League Against Epilepsy (ILAE). The current classification of epilepsy syndromes was developed in 1989. The new ILAE Classification and Definition of Epilepsy Syndromes is a result of huge work of many experts from all over the world. The draft of the new classification is presented on the ILAE website for wide discussion. It includes 4 main sections: 1) classification and definition of epilepsy syndrome with onset in neonates and infants; 2) classification and definition of epilepsy syndromes with onset in childhood; 3) classification and definition of epilepsy syndromes with onset at a variable age; 4) definition of the idiopathic generalized epilepsy syndromes. Each section is based on a thorough analysis of literature and clinical experience of experts. Its main purpose is to identify epilepsy syndromes using the 2017 ILAE classification of epilepsy forms and types of epileptic seizures, as well as to identify specific characteristics of each syndrome to improve clinical diagnosis. For each syndrome, the document provides the details on its epidemiology, clinical manifestations, types of seizures, electroencephalographic features, neuroimaging signs, genetic examination, as well as differential diagnosis with other epilepsy syndromes and various non-epileptic conditions. It introduces mandatory criteria that must be present in order to diagnose the syndrome and alert criteria that are absent in the vast majority of cases within a syndrome, but rarely can be seen. Particular attention is paid to exclusionary criteria that must be absent in order to diagnose the syndrome. When developing the criteria for each epilepsy syndrome, the ILAE Task Force used the latest literature data, including Internet resources and the opinion of experts in this area. The international classification should be applied by specialists from all over the world. It should contain clear and easy-to-understand definitions; the language should be simple and understandable. The new ILAE classification demonstrates revised definitions of well-known electroclinical epilepsy syndromes and proposes a new concept of defining epilepsy syndromes by their etiology (including those syndromes in which pathogenic mutations or structural changes correlate significantly with certain electroclinical phenotype). It also introduces a new etiology-defined class of epilepsy syndromes characterized by specific genetic, metabolic, and structural causes. The document does not cover therapy for epilepsy syndromes; however, for some of them, it specifies the most effective or potentially aggravating antiepileptic drugs. The prospect of further targeted gene therapies development and approval of antiepileptic drugs specific for certain epilepsy syndromes after randomized clinical trials had served as a powerful motivation to introduce the concept of epilepsy syndromes determined primarily by etiology. In conclusion, the authors discuss the Classification and Definition of Epilepsy Syndromes, propose their ideas, comments, suggestions, and observations. This article aims to familiarize a wide range of specialists with the new ILAE classification and its details. In addition to a detailed description of the abovementioned document, the article provides information on the currently existing classification principles for epilepsy and epileptic seizures. There is also a discussion with the authors’ comments on the ILAE Classification and Definition of Epilepsy Syndromes.

ILAE definition of the Idiopathic Generalized Epilepsy Syndromes: Position statement by the ILAE Task Force on Nosology and Definitions.

In 2017, the International League Against Epilepsy (ILAE) Classification of Epilepsies described the "genetic generalized epilepsies" (GGEs), which contained the "idiopathic generalized epilepsies" (IGEs). The goal of this paper is to delineate the four syndromes comprising the IGEs, namely childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We provide updated diagnostic criteria for these IGE syndromes determined by the expert consensus opinion of the ILAE's Task Force on Nosology and Definitions (2017-2021) and international external experts outside our Task Force. We incorporate current knowledge from recent advances in genetic, imaging, and electroencephalographic studies, together with current terminology and classification of seizures and epilepsies. Patients that do not fulfill criteria for one of these syndromes, but that have one, or a combination, of the following generalized seizure types: absence, myoclonic, tonic-clonic and myoclonic-tonic-clonic seizures, with 2.5-5.5 Hz generalized spike-wave should be classified as having GGE. Recognizing these four IGE syndromes as a special grouping among the GGEs is helpful, as they carry prognostic and therapeutic implications.

Digital Neuropsychological Assessment of Cognitive Functions in Patients with Epilepsy.

Cognitive impairment often occurs secondary to epilepsy. This study aims to evaluate the cognitive functions of patients with idiopathic generalized epilepsy (IGE) by using the digital neuropsychological assessment. Seventy-nine patients diagnosed with IGE in the last 10 years in our clinic, who completed at least eight years of education were recruited. Participants who met the criteria were 36 individuals with IGE syndrome as well as 36 healthy individuals between the ages of 18-48. All volunteer participants were administered the standardized mini mental test (SMMT) and the Beck depression scale (BDS). For the neurocognitive assessment, participants completed five tasks in TestMyBrain digital neuropsychology test battery (TMB) which are TMB digit span, TMB choice reaction time test, TMB visual paired associates test, TMB matrix reasoning, and TMB digit symbol matching assessing a variety of cognitive domains. IGE patients showed lower cognitive performance in attention, short-term memory, working memory, visual memory, episodic memory, cognitive processing speed, response selection/inhibition, fluid cognitive ability, and perceptual reasoning domains. The results show that IGE patients have cognitive dysfunction in many cognitive domains. IGE patients performed significantly worse outcomes in some tests of the TMB. In this study, it is aimed to emphasize the necessity of evaluating the cognitive aspects of epilepsy patients, which will be of great importance in their functionality, in addition to providing symptomatic treatment in order to control their seizures.

Clinical study of idiopathic generalized epilepsy syndromes

Idiopathic generalized epilepsies (IGE) are syndromes diagnosed by clinical and electroencephalographic features. There are four syndromes recognized by the International League Against Epilepsy including childhood absence epilepsy (CAE); juvenile absence epilepsy (JAE); juvenile myoclonic epilepsy (JME); and epilepsy with generalized tonic–clonic seizures only (EGTCS). In the current study, we tried to determine distinctive features to distinguish these syndromes from one another.

Assessment of Gene Polymorphism in GABAA1 Receptor among Sudanese Patients with Juvenile Myoclonic Epilepsy (JME)

Introduction: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy syndrome (IGE) with a strong genetic contribution. The main characters of JME are generalized convulsive or an absences seizures proceeded by myoclonic jerks. Gene variant of gamma-aminobutyric acid type A inhibitory receptor speculated to underlay JME etiology.&#x0D; Objective: This study aimed to screen for JME based on the International League against Epilepsy Commission on Classification and Terminology diagnostic criteria and to assess the link of polymorphism in the GABAA receptor gene, GABRA1 to the development of JME in Sudanese patients.&#x0D; Methods: Our epidemiological study enrolled 44 JME patients, only 23 participated in the genetic part and 35 matched healthy controls were also included. Blood genomic DNA was isolated and PCR based- restriction fragment length polymorphism (RFLP) analysis was done. The data obtained were analyzed using computer software SPSS 21rt edition.&#x0D; Results: The frequency of the mutant G allele was found to be 41.5% in patients and 45.5% in the controls. The genotype distribution of A and G alleles among patients were found to be (AA= 39%), (AG=39%) and (GG= 22%) and that of the controls were (AA=40%), (AG=30%) and (GG= 30%).&#x0D; Conclusion: The mutant G allele of the GABAA1 receptor does not affect the development of JME in Sudanese patients but the AG genotype may be a risk factor.

Epilepsy with eyelid myoclonias and Sotos syndrome features in a patient with compound heterozygous missense variants in APC2 gene

Epilepsy with eyelid myoclonias and Sotos syndrome features in a patient with compound heterozygous missense variants in APC2 gene

Predictors of Outcome in Juvenile Myoclonic Epilepsy.

BackgroundJuvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy syndrome, accounting for 10% of all epilepsy. However, there is limited information regarding the predictors of seizure outcome. The aim of this study was to determine the predictors of seizure outcome in JME patients.MethodsA population-based retrospective study of JME patients who were treated at the Department of Neurology of affiliated Zhongshan Hospital, Xiamen University from 2008 to 2013.ResultsSixty-three patients (30 women and 33 men) were enrolled in this study. The median age at seizure onset was 14 years old, and the average duration of epilepsy was 5 years. The onset of JME at age <16 years was found in 63.5% of patients. The epileptiform runs ≥3 s were observed in 35.8% patients. Febrile seizure was noted in 28.9% of patients. Among 63 patients, 40 patients (63.5%) had remission. Multivariate analysis identified the following factors as significant predictors of seizure outcome: the onset of JME at age <16 years, epileptiform runs ≥3 s runs, and febrile seizure.ConclusionThe onset of JME at age <16 years, febrile seizures and epileptiform runs ≥3 s might be associated with poor long-term seizure outcome in patients with JME.

Late-onset idiopathic (genetic) generalized epilepsies: Clinical and EEG findings

PurposeWe investigated the occurrence and clinical characteristics of late-onset idiopathic generalized epilepsies (IGEs). We also provided a statistically meaningful definition for late-onset IGE in this large cohort of patients. MethodsIn this cross-sectional retrospective chart review study, all patients with a clinical diagnosis of IGE were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 until 2019. We defined “late-onset IGE” according to the following equation: those with an age at onset of their seizures above X years [X = mean age at the seizure onset of all patients + 2 × (standard deviation)]. ResultsDuring the study period, 601 patients with IGE were registered at our epilepsy clinic. Late-onset IGE was defined as having an age at onset of above 26 years. Fifteen patients (2.5%) had late-onset IGE. The syndromic diagnosis of these patients included: IGE with absences [6 patients (40%)], generalized tonic-clonic only (GTC-only) [5 patients (33.3%)], and juvenile myoclonic epilepsy (JME) [4 patients (26.7%)]. ConclusionWhile late-onset IGE (IGE with an age at onset of above 26 years) is not common, one should consider the possibility of its occurrence in adults with new-onset seizures. This condition shares many of the clinical and electroencephalograic features of classical IGEs, which supports the hypothesis that IGE syndromes in different age groups share common biological determinants.

Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy.

Once adults with long-standing idiopathic generalised epilepsy have achieved stable seizure remission, patients or physicians may attempt to discontinue their antiepileptic drug treatment. To date, risk of subsequent seizure relapse across the four idiopathic generalised epilepsy syndromes is largely unknown, and so are the clinical variables associated. For this retrospective observational study, 256 adult outpatients with idiopathic generalised epilepsy were evaluated. Data were obtained from outpatient charts and, if possible, from additional telephone or mail interviews. In 84 patients (33%), antiepileptic medication was discontinued at least once. Median patient age at antiepileptic drug withdrawal was 33years, and median duration of subsequent follow-up was 20years. Seizures recurred in 46% of patients after a median latency of 11months. Following multivariable analysis, seizure relapse was independently associated with short duration of seizure remission beforehand. If medication was withdrawn after < 5years of seizure freedom, two-thirds of patients had a seizure relapse, while among those in remission for ≥ 5years, only one-third relapsed. Discontinuation of antiepileptic drug treatment can be successful in every other adult with long-standing idiopathic generalised epilepsy. Short duration of prior seizure remission appears to be a relevant predictor of seizure recurrence.

The electroclinical features of idiopathic generalized epilepsy patients presenting with fixation-off sensitivity.

To determine the electroclinical features of fixation-off sensitivity (FOS) in patients with idiopathic generalized epilepsy (IGE). We searched the EEG database using the terms "fixation-off sensitivity" and "idiopathic generalized epilepsy" over a four-year period from March 2014 to April 2018 in the Xijing Hospital, Xi'an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos. Photic stimulation procedure and neuropsychological testing were performed during video-EEG monitoring. FOS was observed in eight patients with several different IGE syndromes, including four with eyelid myoclonia/Jeavons syndrome, two with juvenile myoclonic epilepsy, one with photosensitivity epilepsy, and one with epilepsy with generalized tonic-clonic seizures only. FOS was associated with seizures in five patients manifesting with eyelid myoclonic, myoclonic, and myoclonic-tonic-clonic seizures, and eyelid myoclonic status. FOS coexisted with photosensitivity in six patients as independent EEG features. Neuropsychological testing revealed transitory cognitive impairments associated with FOS. FOS is associated with several different IGE syndromes and may coexist with photosensitivity in the same patient as independent EEG features. FOS may be associated with both clinical seizures and cognitive impairments. Intermittent photic stimulation and registration of different eye conditions with and without fixation will aid the study of the dynamics of the visual system in epilepsy patients. [Published with video sequences on www.epilepticdisorders.com].

De novo absence status epilepticus in three paediatric patients: a new idiopathic epilepsy syndrome?

Absence status epilepticus (ASE) is a prolonged generalized absence seizure that usually lasts for hours and can even last for days. The main symptom is the altered content of consciousness while the patient may be alert and partly responsive. We describe the electroclinical features, treatment, and evolution of three paediatric patients with de novo ASE with an excellent response to valproic acid (VPA). Three paediatric patients presented with non-convulsive status epilepticus and an acute confusional state with impaired consciousness and EEG abnormalities compatible with typical ASE, associated with generalized spike-and-wave paroxysms at 2.5-4Hz, as the first epileptic manifestation at eight, three, and nine years of age, respectively. No significant personal and/or family history was reported. None of the patients had absence seizures or any other type of seizure before the occurrence of the ASE. All of them responded well to VPA and had a benign disease course. Neuroradiological imaging was normal in all patients. These three cases presented with ASE as the first manifestation of their epilepsy; none of them had any other type of seizure before the event or during their follow-up, which was long-term in one. All patients had an excellent response to VPA. Our three cases presented with generalized typical ASE as the first manifestation of their epilepsy. De novo ASE might be considered as a well-defined idiopathic epilepsy syndrome or a variant of an idiopathic generalized epilepsy syndrome, such as a particular type or variant of childhood absence epilepsy.

The cognitive phenotype of idiopathic generalized epilepsy

ObjectiveDysexecutive traits have been described in idiopathic generalized epilepsy (IGE), but studies mainly focused on juvenile myoclonic epilepsy (JME). To better understand the neuropsychology of IGE, more research is needed on syndromes other than JME, controlling potential confounding factors as the cognitive effects of valproate and epileptic discharges (ED). We describe the neuropsychological profile of a group of patients with different syndromes of IGE including simultaneous video electroencephalography (EEG). MethodsWe performed a comprehensive cognitive and neuropsychiatric evaluation with video-EEG on 61 adults with IGE (JME 19; IGE with generalized tonic–clonic seizures [GTCS] alone [IGE-GTCS] 22; childhood absence epilepsy [CAE] or juvenile absences epilepsy [JAE] persisting in adulthood 20). We compared results between patients (globally and by syndrome) and a control group of 21 individuals (similar age, educational level); p-values were adjusted for multiple testing according to a 0.05 false discovery rate. ResultsPatients obtained significantly lower results than controls on visuospatial working memory, processing speed, cognitive flexibility and strategy, abstract visuospatial reasoning, arithmetic, and acquired knowledge. While CAE/JAE showed the lowest scores on cognitive assessment and highest anxiety index, IGE-GTCS showed the most favorable scores. Most tests were not influenced by valproate intake, and the dose did not correlate with cognitive performance in the test that yielded differences between patients and controls. Epileptic discharges during assessment were not frequent (10 patients, 1–4 tests). SignificanceOur findings suggest that patients with IGE have significantly lower abilities in various executive functions and acquired knowledge, compared to population of same age and education. The low frequency of ED on simultaneous video-EEG and absence of correlation of scores with valproate dose reinforce that the obtained results are due to a cognitive phenotype in IGE. This phenotype may be influenced by syndrome, and patients with CAE/JAE persisting in the adult may have a wider neuropsychiatric impairment.