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Familial adult myoclonus epilepsy (FAME) is a genetic condition characterized by the occurrence of cortical tremor, myoclonus, and epilepsy. To date, there is neither a curative nor a preventive treatment for FAME. Clinical management is essentially symptomatic and based on antiseizure medications (ASMs). The choice of the correct therapeutic option is limited to ASMs that have both an antiseizure and an antimyoclonic effect, such as valproate, levetiracetam, benzodiazepines, and perampanel. However, these medications control seizures well while having a limited effect on myoclonus and cortical tremor. In addition, many ASMs, including sodium channel blockers and gabapentin, are contraindicated in this condition. The ideal therapeutic option would be a precision treatment able to revert the genetic defect underlying it. Nevertheless, this does not seem to be an option that will be available soon., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensus regarding which entities fulfilled criteria for an epilepsy syndrome and to provide definitions for each syndrome. We defined an epilepsy syndrome as "a characteristic cluster of clinical and electroencephalographic features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)." The diagnosis of a syndrome in an individual with epilepsy frequently carries prognostic and treatment implications. Syndromes often have age-dependent presentations and a range of specific comorbidities. This paper describes the guiding principles and process for syndrome identification in both children and adults, and the template of clinical data included for each syndrome. We divided syndromes into typical age at onset, and further characterized them based on seizure and epilepsy types and association with developmental and/or epileptic encephalopathy or progressive neurological deterioration. Definitions for each specific syndrome are contained within the corresponding position papers., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. The incidence of epilepsy is high in this age group and epilepsy is frequently associated with significant comorbidities and mortality. The licensing of syndrome specific antiseizure medications following randomized controlled trials and the development of precision, gene-related therapies are two of the drivers defining the electroclinical phenotypes of syndromes with onset in infancy. The principal aim of this proposal, consistent with the 2017 ILAE Classification of the Epilepsies, is to support epilepsy diagnosis and emphasize the importance of classifying epilepsy in an individual both by syndrome and etiology. For each syndrome, we report epidemiology, clinical course, seizure types, electroencephalography (EEG), neuroimaging, genetics, and differential diagnosis. Syndromes are separated into self-limited syndromes, where there is likely to be spontaneous remission and developmental and epileptic encephalopathies, diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. The emerging class of etiology-specific epilepsy syndromes, where there is a specific etiology for the epilepsy that is associated with a clearly defined, relatively uniform, and distinct clinical phenotype in most affected individuals as well as consistent EEG, neuroimaging, and/or genetic correlates, is presented. The number of etiology-defined syndromes will continue to increase, and these newly described syndromes will in time be incorporated into this classification. The tables summarize mandatory features, cautionary alerts, and exclusionary features for the common syndromes. Guidance is given on the criteria for syndrome diagnosis in resource-limited regions where laboratory confirmation, including EEG, MRI, and genetic testing, might not be available., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

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., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The 2017 International League Against Epilepsy classification has defined a three-tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self-limited focal epilepsies, comprising four syndromes: self-limited epilepsy with centrotemporal spikes, self-limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic-atonic seizures, Lennox-Gastaut syndrome, developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep, hemiconvulsion-hemiplegia-epilepsy syndrome, and febrile infection-related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: We aimed to characterize epilepsy of infancy with migrating focal seizures (EIMFS), a rare, severe early onset developmental epilepsy related to KCNT1 mutation, and to define specific electroencephalography (EEG) markers using EEG quantitative analysis. The ultimate goal would be to improve early diagnosis and to better understand seizure onset and propagation of EIMFS as compared to other early onset developmental epilepsy., Methods: EEG of 7 EIMFS patients with KCNT1 mutations (115 seizures) and 17 patients with other early onset epilepsies (30 seizures) was included in this study. After detection of seizure onset and termination, spatiotemporal characteristics were quantified. Seizure propagation dynamics were analyzed using chronograms and phase coherence., Results: In patients with EIMFS, seizures started and were localized predominantly in temporal and occipital areas, and evolved with a stable frequency (4-10 Hz). Inter- and intrahemispheric migrations were present in 60% of EIMFS seizures with high intraindividual reproducibility of temporospatial dynamics. Interhemispheric migrating seizures spread in 71% from temporal or occipital channels to the homologous contralateral ones, whereas intrahemispheric seizures involved mainly frontotemporal, temporal, and occipital channels. Causality links were present between ictal activities detected under different channels during migrating seizures. Finally, time delay index (based on delays between the different ictal onsets) and phase correlation index (based on coherence of ictal activities) allowed discrimination of EIMFS and non-EIMFS seizures with a specificity of 91.2% and a sensitivity of 84.4%., Significance: We showed that the migrating pattern in EIMFS is not a random process, as suggested previously, and that it is a particular propagation pattern that follows the classical propagation pathways. It is notable that this study reveals specific EEG markers (time delay and phase correlation) accessible to visual evaluation, which will improve EIMFS diagnosis., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue., Methods: All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information., Results: Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups., Significance: HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings., Methods: Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3)., Results: A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection., Significance: This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10 years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography [SEEG]) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible "kindling-like" relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic zone could still be limited to the hamartoma, for which early surgical treatment should be pragmatically considered as a first surgical step., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objective: Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy., Methods: A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated., Results: Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well., Significance: Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objective: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers., Methods: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations., Results: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used., Significance: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for high-quality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) presents clinically with infrequent nocturnal focal seizures, atypical absences related to secondary bilateral synchrony, negative myoclonia, and atonic and rare generalized tonic-clonic seizures. The unique electroencephalography (EEG) pattern found in ECSWS consists of continuous, diffuse, bilateral spike-waves during slow-wave sleep. Despite the eventual disappearance of clinical seizures and EEG abnormalities by adolescence, the prognosis is guarded in most cases because of neuropsychological and behavioral deficits. ECSWS has a heterogeneous etiology (genetic, structural, and unknown). Because epilepsy and electroencephalography (EEG) abnormalities in epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) are self-limited and age related, the need for ongoing medical care and transition to adult care might be questioned. For adolescents in whom etiology remains unknown (possibly genetic) and who experience the disappearance of seizures and EEG abnormalities, there is rarely need for long-term neurologic follow-up, because often a relatively normal cognitive and social evolution follows. However, the majority of patients with structural and possibly "genetic syndromic" etiologies will have persistent cognitive deficits and will need suitable socioeducative care. Therefore, the transition process in ECSWS will depend mainly on etiology and its related features (epileptic active phase duration, and cognitive and behavioral evolution) and revolve around neuropsychological and social support rather than medical and pharmacologic follow-up., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Objectives: Rolandic epilepsies (REs) represent the most frequent epilepsy in childhood. Patients may experience cognitive, speech, language, reading, and behavioral issues. The genetic origin of REs has long been debated. The participation of rare copy number variations (CNVs) in the pathophysiology of various human epilepsies has been increasingly recognized. However, no systematic search for microdeletions or microduplications has been reported in RE so far., Methods: Array comparative genomic hybridization (aCGH) and quantitative polymerase chain reaction (qPCR) were used to analyze the genomic status of a series of 47 unrelated RE patients who displayed various types of electroclinical manifestations., Results: Thirty rare CNVs were detected in 21 RE patients. Two CNVs were de novo, 12 were inherited, and 16 were of unknown inheritance. Each CNV was unique to one given patient, except for a 16p11.2 duplication found in two patients. The CNVs of highest interest comprised or disrupted strong candidate or confirmed genes for epileptic and other neurodevelopmental disorders, including BRWD3, GRIN2A, KCNC3, PRKCE, PRRT2, SHANK1, and TSPAN7., Significance: Patients with REs showed rare microdeletions and microduplications with high frequency and heterogeneity. Whereas only a subset of all genomic alterations found here may actually participate in the phenotype, the novel de novo events as well as several inherited CNVs contain or disrupt genes, some of which are likely to influence the emergence, the presentation, or the comorbidity of RE. The future screening of cohorts of larger size will help in detecting more de novo or recurrent events and in appreciating the possible enrichment of specific CNVs in patients with RE., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: To evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV), a novel high-affinity synaptic vesicle protein 2A ligand that also displays inhibitory activity at neuronal voltage-dependent sodium channels, in adult epilepsy patients with uncontrolled partial-onset seizures., Methods: A phase IIb, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study (N01114; NCT00175929) was conducted in patients aged 16-65 years. To be included in the study, patients were required to have experienced four or more partial-onset seizures during a 4-week prospective baseline, despite treatment with 1-2 concomitant antiepileptic drugs. Patients were randomized in a ratio of 1:1:1 to receive BRV 50 mg/day (BRV50), 150 mg/day (BRV150), or placebo. A 3-week up-titration period was followed by a 7-week maintenance period (total treatment period of 10 weeks)., Key Findings: A total of 157 patients were randomized (intent-to-treat [ITT] population; BRV50 n = 53, BRV150 n = 52, placebo n = 52) and overall 148 (94.3%) completed the study. The percent reduction in baseline-adjusted partial-onset seizure frequency/week over placebo during the 7-week maintenance period (primary efficacy outcome) did not reach statistical significance (14.7% for BRV50 [p = 0.093] and 13.6% for BRV150 [p = 0.124]). However, during the entire 10-week treatment period a statistically significant difference was observed for both BRV groups (17.7% for BRV50 [p = 0.026] and 16.3% for BRV150 [p = 0.043]). The median percent reduction from baseline in partial-onset seizure frequency/week during the maintenance period was 38.2% for BRV50 (p = 0.017) and 30.0% for BRV150 (p = 0.113) versus 18.9% in the placebo group. During the treatment period, this was 34.9% for BRV50 (p = 0.004) and 28.3% for BRV150 (p = 0.070) compared with 16.3% for placebo. Fifty percent responder rates during the maintenance period were 23.1% for placebo compared with 39.6% for BRV50 (odds ratio [OR] 2.17, p = 0.077) and 33.3% for BRV150 (OR 1.66, p = 0.261). During the treatment period, 50% responder rates were 17.3% for placebo compared with 35.8% for BRV50 (OR 2.69, p = 0.038) and 30.8% for BRV150 (OR 2.15, p = 0.114). Nine patients were free from partial-onset seizures during the 10-week treatment period (five patients [9.4%] in the BRV50 group and three [5.8%] in the BRV150 group compared with one patient [1.9%] in the placebo group). Treatment-emergent adverse events (TEAEs) reported during the treatment period were mostly mild-to-moderate with similar incidence across treatment groups (BRV50 36/53, 67.9%; BRV150 35/52, 67.3%; placebo 37/52, 71.2%). The most frequently reported TEAEs in BRV groups were headache, fatigue, nasopharyngitis, nausea, somnolence, and dizziness, although nausea had a higher incidence in the placebo group., Significance: In this double-blind, placebo-controlled, phase IIb study of adjunctive BRV (50 and 150 mg/day) in adults with uncontrolled partial-onset seizures, the primary efficacy analysis did not reach statistical significance; however, statistically significant differences compared with placebo were observed on several secondary efficacy outcomes. BRV was well tolerated., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: The continuous spike and waves during slow-wave sleep syndrome (CSWSS) and the Landau-Kleffner (LKS) syndrome are two rare epileptic encephalopathies sharing common clinical features including seizures and regression. Both CSWSS and LKS can be associated with the electroencephalography pattern of electrical status epilepticus during slow-wave sleep and are part of a clinical continuum that at its benign end also includes rolandic epilepsy (RE) with centrotemporal spikes. The CSWSS and LKS patients can also have behavioral manifestations that overlap the spectrum of autism disorders (ASD). An impairment of brain development and/or maturation with complex interplay between genetic predisposition and nongenetic factors has been suspected. A role for autoimmunity has been proposed but the pathophysiology of CSWSS and of LKS remains uncharacterized., Methods: In recent years, the participation of rare genomic alterations in the susceptibility to epileptic and autistic disorders has been demonstrated. The involvement of copy number variations (CNVs) in 61 CSWSS and LKS patients was questioned using comparative genomic hybridization assays coupled with validation by quantitative polymerase chain reaction (PCR)., Key Findings: Whereas the patients showed highly heterogeneous in genomic architecture, several potentially pathogenic alterations were detected. A large number of these corresponded to genomic regions or genes (ATP13A4, CDH9, CDH13, CNTNAP2, CTNNA3, DIAPH3, GRIN2A, MDGA2, SHANK3) that have been either associated with ASD for most of them, or involved in speech or language impairment, or in RE. Particularly, CNVs encoding cell adhesion proteins (cadherins, protocadherins, contactins, catenins) were detected with high frequency (≈20% of the patients) and significant enrichment (cell adhesion: p = 0.027; cell adhesion molecule binding: p = 9.27 × 10(-7))., Significance: Overall our data bring the first insights into the possible molecular pathophysiology of CSWSS and LKS. The overrepresentation of cell adhesion genes and the strong overlap with the genetic, genomic and molecular ASD networks, provide an exciting and unifying view on the clinical links among CSWSS, LKS, and ASD., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Purpose: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS)., Methods: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered., Key Findings: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS., Significance: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Intermittent photic stimulation (IPS) is a common procedure performed in the electroencephalography (EEG) laboratory in children and adults to detect abnormal epileptogenic sensitivity to flickering light (i.e., photosensitivity). In practice, substantial variability in outcome is anecdotally found due to the many different methods used per laboratory and country. We believe that standardization of procedure, based on scientific and clinical data, should permit reproducible identification and quantification of photosensitivity. We hope that the use of our new algorithm will help in standardizing the IPS procedure, which in turn may more clearly identify and assist monitoring of patients with epilepsy and photosensitivity. Our algorithm goes far beyond that published in 1999 (Epilepsia, 1999a, 40, 75; Neurophysiol Clin, 1999b, 29, 318): it has substantially increased content, detailing technical and logistical aspects of IPS testing and the rationale for many of the steps in the IPS procedure. Furthermore, our latest algorithm incorporates the consensus of repeated scientific meetings of European experts in this field over a period of 6 years with feedback from general neurologists and epileptologists to improve its validity and utility. Accordingly, our European group has provided herein updated algorithms for two different levels of methodology: (1) requirements for defining photosensitivity in patients and in family members of known photosensitive patients and (2) requirements for tailored studies in patients with a clear history of visually induced seizures or complaints, and in those already known to be photosensitive., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD., Methods: Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation., Results: Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene., Discussion: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy.

Epilepsy is a frequent neurologic disease in childhood, characterized by recurrent seizures and sometimes with major effects on social, behavioral, and cognitive development. Childhood focal epilepsies particularly are age-related diseases mainly occurring during developmental critical periods. A complex interplay between brain development and maturation processes and susceptibility genes may contribute to the development of various childhood epileptic syndromes associated with language and cognitive deficits. Indeed, the Landau-Kleffner syndrome (LKS), the continuous spike-and-waves during sleep syndrome (CSWS), and the benign childhood epilepsy with centrotemporal spikes (BCECTS) or benign rolandic epilepsy, are different entities that are considered as part of a single continuous spectrum of disorders. Genetic predisposition with simple to complex modes of inheritance has long been suspected for this wide group of childhood focal epilepsies. Recent reports on the involvement of the SRPX2 and ELP4 genes with possible roles in cell motility, migration, and adhesion have provided first insights into the complex molecular bases of childhood focal epilepsies.

Purpose: This retrospective study aims to review the electroclinical features of patients presenting with eyelid myoclonia (EM) with and without absences., Methods: The Italian chapter of the International League Against Epilepsy (ILAE) has been conducting an electroclinical study of patients with EM. Among these, we searched for and selected the patients presenting with both impairment of intellectual functions and a peculiar ictal electroencephalography (EEG) pattern, that is, a discharge of fast generalized polyspikes/polyspikes and waves., Results: We found 18 patients matching this electroclinical picture. All the patients were photosensitive. All of them had associated generalized, mostly nocturnal, tonic-clonic seizures. During the evolution, 13 patients presented episodes of EM status. Despite adequate antiepileptic treatment, the patients remained drug resistant for many years or throughout the evolution. The degree of impairment of intellectual functions varied from borderline level to moderate mental retardation., Discussion: The patients we described herein can be considered a homogeneous group in the more heterogeneous group of patients presenting with EM. Further clinical and, more probably, genetic studies will clarify whether this condition could be considered a specific and homogeneous condition in the more heterogeneous group of patients presenting with EM.

Purpose: Language-induced epilepsy involves seizure precipitation by speaking, reading, and writing. Seizures are similar to those of reading epilepsy (RE). The nosologic position of language-induced epilepsy is not clear. We performed a clinical and neurophysiological study in a multigenerational family with the association of idiopathic generalized epilepsy (IGE) with ictal stuttering as a manifestation of reflex language-induced epilepsy., Methods: Nine members on three generations were studied. All patients underwent video-polygraphic EEG recordings (awake and during sleep). A standardized protocol was applied to test the effect of language and non-language-related tasks., Results: Six patients presented language-induced jaw jerking that mimicked stuttering and corresponded to focal myoclonus involving facial muscles. This was associated with an IGE phenotype in four of these patients. Focal EEG spikes were found in all six patients by visual analysis and/or back-averaging techniques. The focal spikes were either asymptomatic (when followed by a slow wave) or symptomatic of facial myoclonia (when isolated). Levetiracetam, used as add-on or monotherapy in four patients, suppressed ictal stuttering. One additional case only had a phenotype of IGE without focal features., Conclusions: This family study demonstrates the phenotypic heterogeneity of the association of IGE phenotype with ictal stuttering (language-related reflex seizure). Our data suggest that this particular form of reflex epilepsy related to language has more similarities with generalized epilepsies than with focal ones. Neurophysiological investigations should be performed more systematically in patients with acquired stuttering, especially if there is family history of IGE.

Purpose: To report three patients with drug-resistant nocturnal hypermotor seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal frontal lobe epilepsy (NFLE) or autosomal dominant NLFE (ADNFLE), whose intracerebral EEG ictal onset primarily involved the insula, rather than the mesial or orbital frontal cortex., Methods: Fourteen to 15 intracerebral electrodes were implanted in each patient, primarily sampling the frontal lobes with 80 to 91 recording leads covering the most likely side of seizure onset, and two to six leads placed within the ipsilateral insula. Electrical stimulation was used to test the epileptic threshold of frontal and insular brain regions at the various recording sites., Results: In all three patients, a low-voltage fast activity was recorded within the anterosuperior aspect of the insula at ictal onset, either in isolation, or extending to the nearby frontal operculum in the ADNFLE patient. The role of the insula was further supported in all three patients either by the presence of high-amplitude spikes that clearly predominated over that region (n = 2) or by triggering the patient's typical aura or seizure when applying an electrical stimulation at that site, selectively (n = 2)., Conclusions: The anterosuperior portion of the insula might play a pivotal role in generating nocturnal hypermotor seizures in some patients with nonlesional drug-resistant epilepsy suggesting NFLE or ADNFLE. Whether these patients are amenable to successful surgery remain an open issue.

We report the case of a patient with severe partial epilepsy associated with a focal rolandic, pathologically proven, cortical dysplasia. By measuring intracellular calcium concentrations, functional antiglial non-glutamate receptor 3 (GluR3) autoantibodies were identified in the serum of this patient. Antineuronal autoantibodies, which interfere with GluR3-receptor function, also were detected. This observation provides new clues about the involvement of immunologic mechanisms in epileptic disorders.

Since the first case of videogame (VG) epilepsy was reported in 1981, many cases of seizures triggered by VGs were reported, not only in photosensitive, but also in non-photosensitive children and adolescents with epilepsy. We provide an overview of the literature with overall conclusions and recommendations regarding VG playing. Specific preventive measures concerning the physical characteristics of images included in commercially available VGs (flash rate, choice of colors, patterns, and contrast) can lead in the future to a clear decrease of this problem. In addition to the positive effect of such measures, the collaborative studies performed in France and in the rest of Europe have stressed the importance of a safe distance to the screen of > or = 2 m, and the less provocative role of 100-Hz screens.

Purpose: Dysembryoplastic neuroepithelial tumors (DNTs) are a group of glioneuronal supratentorial and intracortical lesions often associated with the early onset of intractable and crippling partial seizures. They are characterized by their location, multinodular architecture, and heterogeneous cell composition, with a specific glioneuronal element in the specific form. Foci of cortical dysplasia may be associated with the tumoral lesion, and identifying the presence and the extent of cortical dysplasia is not always easy on magnetic resonance images (MRIs). The purpose of this article is to evaluate, retrospectively, the usefulness of ictal single-photon emission computed tomography (SPECT) imaging to assess the presence and the extent of cortical dysplasia associated with DNTs in nine patients with intractable temporal lobe epilepsy related to histopathologically confirmed DNTs., Methods: The results of the subtraction of ictal and interictal SPECT coregistered to MRI (SISCOM) were compared with the results of the examinations of pathological material after surgery., Results: SISCOM showed a strongly hyperperfused area corresponding anatomically to electroclinical abnormalities and to the location of DNTs on MRI. A circumscribed hyperperfusion was present in DNTs without cortical dysplasia, limited to the location of the tumor on MRI. In cases of associated cortical dysplasia, a widespread hyperperfusion including areas corresponding to normal perilesional regions on MRI was found., Conclusions: SISCOM, used among presurgical investigations, contributes to detecting cortical dysplasia associated with DNTs. Concordance between the symptomatogenic zone (defined from the medical history and electroclinical data), MRI scans, SISCOM pattern, and complete resection of the epileptic zone was predictive of a good postsurgical outcome.

The diagnosis, treatment, and prognosis of seizure disorders depend on the correct identification of epileptic syndromes. Partial epilepsies are heterogeneous and can be divided into idiopathic, cryptogenic, and symptomatic epilepsies. The most common of the idiopathic localization-related epilepsies is benign epilepsy with rolandic or centrotemporal spikes (BECTS). Seizures remain rare and the use of antiepileptic drug (AED) treatment in all patients does not appear justified. Children who present with some of the electroclinical characteristics of BECTS may also display severe unusual neurologic, neuropsychological, or atypical symptoms. In some cases, carbamazepine has been implicated as a triggering factor. Primary reading epilepsy and idiopathic occipital lobe epilepsies with photosensitivity are examples of an overlap between idiopathic localization-related and generalized epilepsies and respond well to sodium valproate. Autosomal dominant nocturnal frontal lobe epilepsy and benign familial infantile convulsions are recently described syndromes, differing in several ways from classical idiopathic localization-related epileptic syndromes. In cryptogenic or symptomatic epilepsy, the topography of the epileptogenic zone might influence drug efficacy. An individualized approach to AED selection, tailored to each patient's needs, should be used. Resistance of seizures to antiepileptic therapy may be due to diagnostic and/or treatment error or may be the result of noncompliance. Increasing the dosage, discontinuation or replacement of a drug, or addition of a second drug is indicated in truly resistant cases. The use of more than two AEDs rarely optimizes seizure control, and in some cases reduction of treatment may improve seizure control while lessening side effects. EEG-video assessment of patients with refractory epilepsy is important. Indications for and timing of epilepsy surgery should be reconsidered. Surgical therapy should probably be used more often and earlier than it is at present.

A 5-year-old boy with generalized absence seizures was treated with valproate (VPA), 30 mg/kg/day. One month after VPA introduction, routine examination showed moderate reduction in fibrinogen and prolonged partial thromboplastin time (PTT). The search for lupus anticoagulant (LAC) was negative. After 10 months of VPA treatment, seizures persisted, and lamotrigine (LTG), 2 mg/kg/day, was progressively given with VPA. Seizures disappeared, but PTT was more prolonged than before LTG introduction. The search for LAC was positive, and enzyme-linked immunosorbent assays (ELISAs) for immunoglobulin G (IgG) anticardiolipid antibodies were positive. Serum autoantibody screen and rheumatoid factor were negative; serum complement was normal. LAC eventually disappeared with VPA discontinuation. We believe that LTG may have exacerbated an initially mild immune response induced by VPA without clinical evidence of systemic disease. We therefore suggest that careful surveillance for LAC and systemic disease should be instituted when VPA is used with LTG.

Purpose: In this study we tried to find a correlation between the clinical severity and memory performances, by comparing proton magnetic resonance (MR) spectroscopy and T2 relaxation time measurements in the hippocampi, in a homogeneous group of 27 patients with unilateral mesial temporal lobe epilepsy with ipsilateral hippocampal sclerosis on MR imaging, with a view to answer the following questions: (a) how sensitive is this approach for the assessment of the apparently normal contralateral hippocampus, (b) do the results relate to the clinical severity, and (c) does it allow evaluation of the degree of hippocampal dysfunction., Methods: Volume-selective proton MR spectroscopy of the head of both hippocampi was performed at 3 T, by using the PRESS sequence, with an echo time of 135 ms, to estimate NAA/(Cho + Cr) ratios. The relaxation times were measured at 0.28 T, by using a conventional Carr-Purcell-Meiboom-Gill sequence, with a repetition time of 2,000 ms, an echo time of 15 ms, and 48 echoes., Results: The combination of NAA/(Cho + Cr) ratio and T2 relaxation time values was allowed to classify contralateral hippocampus abnormalities in two groups: first, decreased NAA/(Cho + Cr) ratio with strongly increased T2 relaxation time values corresponding to abnormalities observed in sclerotic ipsilateral hippocampi; and second, decreased NAA/(Cho + Cr) ratio with normal or slightly increased T2 relaxation time values. Whereas the NAA/(Cho + Cr) ratio or T2 relaxation time value alone was not correlated with memory performances, their association shows that left hippocampal injury evaluated both by NAA and T2 relaxation time measurements was clearly correlated with verbal memory scores, and right hippocampal injury, with visual memory scores. On the other hand, the maximal seizure frequency reported by the patients was correlated with ipsilateral NAA/(Cho + Cr) ratio and T2 relaxation time values but not with contralateral results., Conclusions: We showed that the combination of NAA and T2 relaxation time measurements can be used to examine the degree of ipsi- and contralateral hippocampal dysfunction or injuries and their relations with memory performances in the presurgical evaluation of patients.

Purpose: The prognosis of benign epilepsy with centrotemporal spikes (BECTS) is always favorable as far as the epilepsy is concerned. However, some data suggest that affected children may be at risk for minor cognitive impairment. We report here the longitudinal study of a young girl demonstrating that BECTS also may be associated with severe motor disturbances., Methods: BECTS (rare left oromotor seizures, right rolandic spike-waves activated during sleep) started at the age of 3 years 6 months in a girl with normal initial psychomotor development. Her clinical, neuropsychological, and EEG status was assessed every 3-6 months. Regional cerebral glucose metabolism was measured by using the [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) method., Results: Between the age of 5 and 6 years, the girl had (a) increased seizure frequency; (b) brief perioral and palpebral myoclonic jerks, concomitant with the spike component of interictal spike-waves, and (c) persistent but fluctuating oromotor deficits (drooling, dysarthria, dysphagia). The EEG showed a marked increase in abundance and amplitude of wake and sleep interictal abnormalities, which became bilateral. Awake FDG-PET revealed a bilateral increase of glucose metabolism in opercular regions. A complete and definitive EEG and clinical remission occurred at age 5 years 11 months and has persisted since (present age, 7 years 9 months)., Conclusions: This case confirms that during BECTS, epileptiform dysfunctions within rolandic areas may induce "interictal" positive or negative oromotor symptoms, independent of classic seizures.

Purpose: In rodents, specific motor components of generalized convulsive seizures depend on two distinct anatomic substrates: (a) forebrain networks are responsible for facial and forelimb clonus with or without rearing and falling; and (b) brainstem networks are responsible for running-bouncing fits and tonic convulsions. To investigate the requirement of proprioceptive inputs in the generation of these two different types of seizures, we compared the effects of neuromuscular blockade by D-tubocurarine on the EEG expression of brainstem- and forebrain-triggered seizures., Methods: Unilateral electrical stimulations were applied for 50 consecutive days in freely moving male adult rats through a bipolar electrode aimed at the dorsal hippocampus (n = 5), the occipital cortex (n = 4), the inferior colliculus (n = 6), or the midbrain reticular formation (n = 6). Two days after the last stimulation, rats were paralyzed with d-tubocurarine and stimulated in the same way., Results: In brainstem structures, the first electrical stimulation induced tonic seizures concomitant with low-voltage cortical activity; repetition of daily stimulations progressively induced tonic-clonic seizures associated with high-amplitude cortical spike-wave discharges. After immobilization by d-tubocurarine, brainstem stimulations failed to induce any EEG paroxysm. In forebrain structures, repeated electrical stimulations produced a classic kindling with progressive occurrence of clonic seizures associated with large cortical discharges; d-tubocurarine left unchanged the EEG pattern of these latter seizures., Conclusions: These data suggest that proprioceptive reafferentation resulting from movement is necessary for the generation of self-sustained brainstem seizures but is not implicated in the elaboration of forebrain seizures.

Three right-handed male children (aged 5, 6, and 11 years) with signs, symptoms and/or history of the syndrome of acquired aphasia-epilepsy (Landau-Kleffner syndrome) were studied during drug-induced, electroencephalographically (EEG)-monitored sleep by positron-emission tomography (PET) and the [18F]fluorodeoxyglucose (FDG) method. Our data demonstrate that in Landau-Kleffner syndrome, cerebral glucose utilization is not normal during sleep. The metabolic pattern varied between the children but the metabolic disturbances always predominated over the temporal lobes. They were right-sided, left-sided, or bilateral. In the two first patients, EEG recordings showed continuous spike-and-wave discharges during sleep and a right-greater-than-left asymmetry was observed in temporal areas. In patient 1, the asymmetry was associated with a relative increase of glucose utilization of the right posterior temporal region. In patient 2, the glucose utilization was relatively decreased in the left anterotemporal and left perisylvian regions. In patient 3, the sleep EEG showed no discharge and no significant asymmetry was observed; however, glucose utilization of both temporal lobes was decreased. Lower metabolic rates in subcortical structures than in cortex were also noted in the three children. This metabolic pattern may be related to the maturation of the central nervous system (CNS).

Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae.

In five children with normal initial psychomotor development, a Landau-Kleffner syndrome appeared at age 3-7 years. No neuroanatomic lesions were noted. Aphasia and hyperkinesia were isolated in three patients and associated with global regression of higher cortical functions in one patient. Massive intellectual deterioration and psychotic behavior were associated with transient aphasia in one patient. The epilepsy (focal motor and generalized tonic-clonic seizures, subclinical EEG focal seizures during sleep, and atypical absences) always regressed spontaneously or with antiepileptic drug (AED) treatment. The EEG in waking patients showed focal and generalized spike-wave discharges on a normal background rhythm. Discharge topography and pattern changed frequently. During sleep, discharges always increased. At some time during syndrome development, all patients had bilateral spike-waves for greater than 85% of the sleep period, while at other times the discharges were discontinuous or continuous but focal or unilaterally hemispheric. Discharge topography and abundance changed from night to night. The abnormal EEG and the impaired higher functions developed and regressed together, but not with strict temporal correlation. Our own experience suggests that the Landau-Kleffner syndrome and epilepsy with continuous spike-wave activity in slow-wave sleep cannot be clearly differentiated. They may be different points on the spectrum of a single syndrome.