[Epileptic syndromes in pediatrics. What's new?] / Síndromes epilépticos en pediatría ¿Qué hay de nuevo?

The classification of epilepsy syndromes in pediatrics has undergone significant changes. In 2017, the International League Against Epilepsy Task Force on Nosology and Definitions proposed a new classification and definition and established mandatory, exclusionary, and alert criteria for the diagnosis of the different syndromes. The goal of this article is not to provide an extensive review of each syndrome, but to focus on syndromes that suffered important changes in terminology and/or when consensus or new methods to improve diagnosis and treatment have been designed.

La clasificación de síndromes epilépticos en pediatría ha sufrido cambios significativos. En el 2017, la Comisión en Nosología y Definiciones de la Liga Internacional Contra La Epilepsia propuso una nueva clasificación y definición y estableció criterios, mandatarios, de exclusión y de alerta para los diferentes síndromes. El objetivo de este artículo no es revisar detalladamente cada uno de estos síndromes, pero enfatizar en los que han sufrido cambios importantes en terminología o en los cuales se ha obtenido consenso o se han diseñado nuevos métodos para optimizar el diagnóstico y tratamiento.

Clinical profile and treatment outcome of epilepsy syndromes in children: A hospital-based study in Eastern Nepal.

Objective: It is often difficult to diagnose epilepsy syndromes in resource-limited settings. This study was aimed to investigate the prospect of ascertaining the diagnosis, clinical profile, and treatment outcomes of epilepsy syndromes (ESs) among children in a resource-limited setting. Methods: This was a descriptive study done from 01/07/2009 to 15/06/2017 among children (1-17 years of age) with unprovoked seizures presenting to the pediatric neurology clinic of a university hospital in eastern Nepal. Diagnosis, classification, and treatment of seizures were based upon International League Against Epilepsy guidelines. Results: Of 768 children with unprovoked seizures, 120 (15.6%) were diagnosed as ES. The age of onset of seizure was unique for each ES. Developmental delay and cerebral palsy were present in 47.5% and 28.3% children, respectively. Common ESs were West syndrome (WS)-26.7%, generalized tonic-clonic seizures alone (GTCSA)-21.7%, self-limited childhood epilepsy with centrotemporal spikes (SLCECTS)-12.5%, childhood absence epilepsy (CAE)-10.0%, Lennox-Gastaut syndrome (LGS)-10.0%, other developmental and epileptic encephalopathies (DEE)-5.8%, self-limited familial infantile epilepsy (SLFIE)-4.2%, and juvenile myoclonic epilepsy (JME)-3.3%. Among children with known outcomes (87/120), overall response to pharmacotherapy and to monotherapy was observed in 72.4% (63/87) and 57.5% (50/87) children, respectively. All children with GTCSA, SLFIE, genetic epilepsy with febrile seizure plus (GEFS+), CAE, SLCECTS, and JME responded to pharmacotherapy and they had normal computerized tomography scans of the brain. Seizures were largely pharmaco-resistant in progressive myoclonus epilepsy (PME)-100.0%, LGS-73.0%, WS-52.0%, and other DEEs-40%. Significance: A reasonable proportion (15.6%) of unprovoked seizures could be classified into specific ES despite limited diagnostic resources. WS was the most common ES. GTCSA, SLCECTS, CAE, and LGS were other common ESs. GTCSA, SLFIE, CAE, SLCECTS, GEFS+, and JME were largely pharmaco-responsive. PME, WS, and LGS were relatively pharmaco-resistant. Electro-clinical diagnosis of certain ES avoids the necessity of neuroimaging.

Ambulatory EEG to Classify the Epilepsy Syndrome.

SUMMARY: Recording of interictal epileptiform discharges to classify the epilepsy syndrome is one of the most common indications for ambulatory EEG. Ambulatory EEG has superior sampling compared with standard EEG recordings and advantages in terms of cost-effectiveness and convenience compared with a prolonged inpatient EEG study. Ambulatory EEG allows for EEG recording in all sleep stages and transitional states, which can be very helpful in capturing interictal epileptiform discharges. In the absence of interictal epileptiform discharges or in patients with atypical events, the characterization of an epilepsy syndrome may require recording of the habitual events. Diagnostic ambulatory EEG can be a useful alternative to inpatient video-EEG monitoring in a selected number of patients with frequent events who do not require medication taper or seizure testing for surgical localization.

Quantitative analysis of phenotypic elements augments traditional electroclinical classification of common familial epilepsies.

OBJECTIVE: Classification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks. METHODS: We used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes. RESULTS: A total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types. SIGNIFICANCE: Quantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms.

Implementation of the new ILAE classification of epilepsies into clinical practice - A cohort study.

PURPOSE: Appropriate management of patients with epilepsy requires precise classification of their disease. Implementation of the recent International League Against Epilepsy (ILAE) classification of seizures and epilepsies may affect data on the relative proportions of specific types of seizures or epilepsies and should be tested in everyday practice. The aim of the study was to determine the prevalence of specific epilepsy types, syndromes, and etiologies, as defined by the new ILAE classification, in a large cohort of adult patients with epilepsy. MATERIAL AND METHODS: The single-center cohort study involved consecutive adult patients with epilepsy seen at the university epilepsy clinic. Information about medical history, neurological examination, neuroimaging, electroencephalography (EEG), genetic tests, epilepsy treatment, and other investigations was collected from medical records and prospectively updated if necessary. Epilepsy types and etiology, as well as epileptic syndromes, were classified according to the new ILAE classifications. RESULTS: We studied 653 patients (mean age: 37.2 years, 59.9% were women). Epilepsy was classified as focal in 458 cases (70.2%), generalized in 155 subjects (23.7%), or as combined focal and generalized in 11 patients (1.7%). The epilepsy type was labeled as unknown in 29 (4.4%) patients. A definite cause of epilepsy was identified in 59.4% of the cases, with a structural etiology (n = 179, 27.4%) and genetic or presumed genetic etiology (n = 169, 25.9%) being the most common. In 167 (25.5%) patients, specific epilepsy syndromes, mostly genetic generalized epilepsy syndromes, were diagnosed. CONCLUSION: The use of the recent ILAE classification of seizures and epilepsies in the cohort of patients with epilepsy seen in single epilepsy center enabled unequivocal characterization of epilepsy type in >95% of patients. A definite etiology of epilepsy could be established in about 60% of patients.

Epilepsy Overview and Revised Classification of Seizures and Epilepsies.

PURPOSE OF REVIEW: The classification of seizures, epilepsies, and epilepsy syndromes creates a framework for clinicians, researchers, and patients and their families. This classification has evolved over the years, and in 2017 the International League Against Epilepsy (ILAE) published an operational classification of seizures and epilepsies. Understanding this classification is important in the diagnosis, treatment, and understanding of seizures and epilepsies, including epilepsy incidence. RECENT FINDINGS: The 2017 ILAE classification system builds on newly formulated definitions of seizures and epilepsy. Seizure classification begins by determining whether the initial manifestations of the seizure are focal or generalized. If the onset of the seizure is missed or unclear, the seizure is of unknown onset. Focal seizures are classified according to the individual's level of awareness, the most prominent motor or nonmotor features of the seizure, and whether the focal seizure evolves to a bilateral tonic-clonic seizure. Similarly, generalized seizures are classified according to motor or nonmotor manifestations. Motor seizures are either tonic-clonic or other motor seizures. Nonmotor generalized seizures primarily refer to absence seizures. Similar to seizure classification, the epilepsies can be classified as focal or generalized. In addition, the new classification system recognizes two new categories: combined generalized and focal epilepsy and unknown epilepsy. The concept of an epilepsy syndrome has been introduced under the new classification system and refers to a cluster of features incorporating seizure types, EEG, imaging, and other features including genetics. The new classification system emphasizes the etiology of seizures and epilepsies. SUMMARY: The recent ILAE seizure and epilepsy classification system aims to create a framework to better classify seizures and the epilepsies. Universal adoption and implementation of this system will enable patients, their families, clinicians, and researchers to better define and treat the epilepsies. Incidence studies have not generally classified seizures and the epilepsies, and use of this classification system, which emphasizes etiology, will lead to a better understanding of epilepsy incidence.

Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.

We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.

New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES): State of the art and perspectives.

We report the proceedings of the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. To promote awareness of this condition and foster research efforts, we conveyed the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. The conference was supported by The NORSE Institute (http://www.norseinstitute.org). This article summarizes the discussions that were held during the Symposium and presents our strategy to unravel the cause of these disorders and to improve patient care. The standardized definitions for these disorders that have been developed, are required to improve communication and facilitate the development of multicenter registries and biobanks. A distinction between childhood- and adult-onset forms of the syndrome is not supported by strong scientific evidence and it is argued that both should be studied together. Although the pathophysiology remains elusive, nascent evidence suggests a role for a postinfectious cytokine-mediated mechanism, which should be further investigated. It also appears important to develop tools for their early recognition and prompt treatment. Recent evidence suggests that specific electroencephalography (EEG) features might be helpful. The optimal treatment options remain to be determined; immune therapies are usually disappointing, but the ketogenic diet has proved effective in uncontrolled trials. NORSE and FIRES represent a very delicate clinical situation with specific communication issues between physicians and with patients and families. Standardized consensus definitions and a multidisciplinary multicenter strategy will help research efforts and improve clinical care for patients with NORSE and FIRES.

[Epileptic spasms in infants. Beyond hypsarrhythmia]. / Espasmos epilepticos en el lactante. Mas alla de la hipsarritmia.

Epileptic spasms are the most frequent type of epileptic seizures in infants. They can also occur beyond the period of infancy, within the context of other epileptic encephalopathies or as an expression of a focal or generalised epilepsy. The clinical semiology of epileptic spasms varies greatly. They sometimes consist of very subtle clinical manifestations, which occur in series, without the typical axorhizomelic contraction, or in association with focal seizures. The critical EEG correlate is also very variable and basically consists of the combination of a hypervoltage slow wave, a bout of rapid low-amplitude activity or a diffuse attenuation of the trace. The electromyographic recording of both deltoids during the EEG-video study helps to detect clinically subtle spasms and to define certain features of them that are clinically hard to determine. The classic interictal EEG pattern of hypsarrhythmia, or one of its variants, is not always present. Epileptic spasms can sometimes be mistaken for another type of paroxysmal episodes that can be epileptic or non-epileptic, and the EEG-video study may play a key role for the differential diagnosis. Taken together, the findings from the EEG-video study allow an adequate diagnosis and classification of the different epileptic seizures and syndromes, which can optimise both the therapeutic management and aetiological investigation.

TITLE: Espasmos epilepticos en el lactante. Mas alla de la hipsarritmia.Los espasmos epilepticos son el tipo de crisis epileptica mas frecuente en los lactantes. Tambien pueden ocurrir mas alla del periodo del lactante, en el contexto de otras encefalopatias epilepticas o como expresion de una epilepsia focal o generalizada. La semiologia clinica de los espasmos epilepticos es muy variable. En ocasiones consisten en manifestaciones clinicas muy sutiles, que ocurren en series, sin la contraccion axorrizomelica tipica, o bien se asocian a crisis focales. El correlato EEG critico tambien es muy variable y consiste basicamente en la combinacion de una onda lenta hipervoltada, un brote de actividad rapida de baja amplitud o una atenuacion difusa del trazado. El registro electromiografico de ambos deltoides durante el estudio video-EEG ayuda a detectar espasmos clinicamente sutiles y definir ciertas caracteristicas de estos, clinicamente dificiles de determinar. El clasico patron EEG intercritico de hipsarritmia, o alguna de sus variantes, no siempre esta presente. En ocasiones, los espasmos epilepticos pueden confundirse con otro tipo de episodios paroxisticos tanto epilepticos como no epilepticos, y el estudio video-EEG puede ser clave para el diagnostico diferencial. El conjunto de los hallazgos de los estudios video-EEG permite diagnosticar y clasificar adecuadamente las distintas crisis y sindromes epilepticos, lo que puede optimizar tanto el abordaje terapeutico como la investigacion etiologica.

[A study of epilepsy according to the age at onset and monitored for 3 years in a regional reference paediatric neurology unit]. / Estudio de las epilepsias según la edad de inicio, controladas durante 3 años en una unidad de neuropediatría de referencia regional.

OBJECTIVE: A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. PATIENTS AND METHODS: Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. RESULTS: A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. CONCLUSIONS: The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies.

PCDH19-related epilepsy and Dravet Syndrome: Face-off between two early-onset epilepsies with fever sensitivity.

Aim of this study is to compare PCDH19-related epilepsy and Dravet Syndrome (DS) in order to find out differences between these two infantile epilepsies with fever sensitivity. We retrospectively reviewed the medical records of 15 patients with PCDH19-related epilepsy and 19 with DS. Comparisons were performed with Fisher's exact test or Student's t-test. Females prevailed in PCDH19-related epilepsy. Epilepsy onset was earlier in DS (5.0+2.1 vs 11.2+7.0months; p<0.05). The second seizure/cluster occurred after a longer latency in PCDH19-related epilepsy rather than in DS (10.1±13.6 vs 2.2±2.1months; p<0.05). Seizures were mainly single and prolonged seizures in DS, and brief and clustered in PCDH19-related epilepsy. Myoclonic and clonic seizures have been found only in DS. Other types of seizures were found in both epilepsies with a prevalence of GTCS and atypical absences in DS, and focal motor and hypomotor seizures in PCDH19-related epilepsy. Seizures with affective symptoms have been confirmed to be typical of PCDH19-related epilepsy. Status Epilepticus equally occurred in both groups. Photosensitivity was detected only in DS. No differences were found about the presence of intellectual disabilities and behavioral disturbances. We were able to find out some distinctive features, which could address the diagnosis towards DS or PCDH19-related epilepsy, since first manifestation. These considerations suggest to definitively considering PCDH19 gene as cause of a proper epileptic phenotype.