DOCSLIB.ORG

Recent Developments in the Genetics of Childhood Epileptic Encephalopathies: Impact in Clinical Practice

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recent Developments in the Genetics of Childhood Epileptic Encephalopathies: Impact in Clinical Practice DOI: 10.1590/0004-282X20150122 VIEW AND REVIEW Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice Desenvolvimentos recentes na genética das encefalopatias epilépticas da infância: impacto na prática clínica Marina C. Gonsales1, Maria Augusta Montenegro2, Camila V. Soler1, Ana Carolina Coan,2, Marilisa M. Guerreiro2, Iscia Lopes-Cendes1 ABSTRacT Recent advances in molecular genetics led to the discovery of several genes for childhood epileptic encephalopathies (CEEs). As the knowledge about the genes associated with this group of disorders develops, it becomes evident that CEEs present a number of specific genetic characteristics, which will influence the use of molecular testing for clinical purposes. Among these, there are the presence of marked genetic heterogeneity and the high frequency of de novo mutations. Therefore, the main objectives of this review paper are to present and discuss current knowledge regarding i) new genetic findings in CEEs, ii) phenotype-genotype correlations in different forms of CEEs; and, most importantly, iii) the impact of these new findings in clinical practice. Accompanying this text we have included a comprehensive table, containing the list of genes currently known to be involved in the etiology of CEEs. Keywords: Dravet syndrome, Ohtahara syndrome, West syndrome, Lennox-Gastaut syndrome, Doose syndrome, Landau-Kleffner syndrome. RESUMO Os avanços recentes em genética molecular permitiram a descoberta de vários genes para encefalopatias epilépticas da infância (EEIs). À medida que o conhecimento sobre os genes associados a este grupo de doenças se desenvolve, torna-se evidente que as EEIs apresentam uma série de características genéticas específicas, o que influencia o uso do teste molecular para fins clínicos. Entre as EEIs, há a presença de acentuada heterogeneidade genética e alta frequência de mutações de novo. Assim, os principais objetivos deste trabalho de revisão são apresentar e discutir o conhecimento atual a respeito de i) novas descobertas em genética molecular das EEIs, ii) correlações fenótipo-genótipo nas diferentes formas de EEIs; e, mais importante, iii) o impacto desses novos achados genéticos na prática clínica. Acompanhando o texto, incluímos uma tabela contendo a lista de genes conhecidos atualmente como envolvidos na etiologia da EEIs. Palavras-chave: síndrome de Dravet, síndrome de Ohtahara, síndrome de West, síndrome de Lennox-Gastaut, síndrome de Doose, síndrome de Landau-Kleffner. The encephalopathic effects of epileptic activity may oc- Although the damaging effect of seizures can potentially hap- cur in association with any form of epilepsy; however, it is pen in any form of epilepsy, in some syndromes this impair- more often present in a number of syndromes called child- ment is virtually always present. According to current classi- hood epileptic encephalopathies (CEEs). CEEs are conditions fication1, the following syndromes are considered CEEs: early in which “the epileptic activity itself may contribute to severe myoclonic encephalopathy (EME), Ohtahara syndrome (OS), cognitive and behavioral impairment above and beyond what epilepsy of infancy with migrating focal seizures (EIMFS), might be expected from the underlying pathology alone (e.g., West syndrome (WS), Dravet syndrome, Doose syndrome or cortical malformation), and these can worsen over time”1. epilepsy with myoclonic atonic (previously astatic) seizures, 1Universidade de Campinas, Instituto Brasileiro de Neurociências e Neurotecnologia, Faculdade de Ciências Médicas, Departamento de Genética Médica, Campinas SP, Brazil; 2Universidade de Campinas, Instituto Brasileiro de Neurociências e Neurotecnologia, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil. Correspondence: Iscia Lopes-Cendes; Rua Tessalia Vieira de Camargo, 126; Cidade Universitária Zeferino Vaz / UNICAMP; 13083-887 Campinas SP, Brasil; E-mail: icendes@unicamp.br Conflict of interest: There is no conflict of interest to declare. Support: This work was supported by research grants from FAPESP and CNPq. MCG is supported by a fellowship from FAPESP and CVS is supported by a studentship from CNPq. Received 29 May 2015; Received in final form 01 July 2015; Accepted 20 July 2015. 1 Lennox-Gastaut syndrome (LGS), epileptic encephalopathy atypical absences, generalized tonic clonic and focal), and EEG with continuous spike-and-wave during sleep (CSWS), and during wakefulness showing diffuse slow spike-and-waves Landau-Kleffner syndrome (LKS). As widely recognized, (<2.5Hz). During sleep, EEG shows bursts of generalized fast each one of these different clinical entities have specific char- spikes around 10 Hz4. Although LGS can evolve from WS, it acteristics, including mainly clinical and EEG features, which may occur in a previously epilepsy free child. Both WS and make it possible to clinically recognize them; however, recent LGS can be associated with structural lesions such as mal- developments in the field of molecular genetics are helping formations of cortical development, vascular lesions, meta- to determine that there are many intermediary phenotypes, bolic disorders, etc. However, several patients present with a which can represent a great diagnostic challenge to clini- normal MRI. Therefore, determining the etiology of CEEs in cians. Patients presenting these transitional or less charac- these patients represents an additional challenge. teristic phenotypes are probably those who will benefit most Doose syndrome, or epilepsy with myoclonic atonic (pre- of the recently available genetic diagnostic tools, which will viously astatic) seizures, is characterized by multiple sei- help determining diagnosis and establishing an etiology. zure types such as atypical absence, atonic, tonic and myo- However, even for patients with a clinically well-defined syn- clonic astatic seizures. Its onset is between 7 months and drome within the group of CEEs a positive genetic test can 6 years-old5, and the prognosis is variable. Disturbances in define etiology. Therefore, the main objective of this review cognitive and psychomotor skills are often present. The EEG is to present and discuss current knowledge regarding i) new remains the best diagnostic tool available. molecular genetic findings in this group of disorders; ii) the Dravet syndrome was described in 1978 under the name complex phenotype-genotype correlations observed in the of severe myoclonic epilepsy of infancy6. It is characterized CEEs; and, most importantly, iii) the impact of these new ge- by febrile and afebrile generalized and unilateral, clonic or netic findings in clinical practice. tonic clonic, seizures, which occur in the first year of life in an otherwise normal infant. These can be later associat- ed with myoclonus, atypical absences, and partial seizures, MOST COMMON CEES and high sensitivity even to low-degree fever is observed6,7. Between the first and fourth years of life, some degree of cog- Early myoclonic encephalopathy (EME) is a neonatal epi- nitive impairment and behavior abnormality is often present. lepsy syndrome characterized by onset of myoclonic seizures Seizures are usually refractory to antiepileptic drug treat- usually within the first month of life and abnormal neurologi- ment. Photosensitivity may be present. However, photosensi- cal signs at birth or at the moment of seizure onset2. The EEG tivity can be difficult to evaluate because it may not be pres- presents with suppression-burst pattern with short paroxys- ent during the whole course of the disease6. mal bursts and longer periods of suppression, enhanced dur- Epileptic encephalopathy with continuous spike-and-wave ing sleep2. The syndrome has a poor prognosis with progres- during sleep (CSWS) is characterized by a typical EEG find- sive deterioration and early death. ing of continuous spike-and-wave discharges (usually dif- Ohtahara syndrome (OS), also called early infantile epilep- fuse, but sometimes focal) occurring in at least 85% of slow tic encephalopathy, is an age-dependent epileptic encephalop- sleep in children with focal or, eventually, generalized sei- athy characterized by tonic seizures with onset at the neonatal zures (electrical status epilepticus of sleep, ESES). Seizure period and EEG showing suppression-burst pattern with lon- onset usually occurs between 2 and 12 years and there is a ger periods of bursts and shorter periods of suppression2. The marked neurological deterioration in cognitive, behavioral prognosis is poor, with significant neurological impairment or and/or motor domains8. The treatment must aim the disap- death. Children with OS might evolve to West syndrome2. pearance of the ESES, which is the mechanism responsible Epilepsy of infancy with migrating focal seizures (EIMFS) for the encephalopathy. is a rare epileptic syndrome characterized by onset of multifo- Landau-Kleffner syndrome (LKS) or syndrome of acquired cal focal seizures within the first 6 months of life and an ictal aphasia with convulsive disorder in children is an epileptic en- EEG demonstrating seizures independently arising and mov- cephalopathy that occurs in previously normal children with ing sequentially from both hemispheres. The syndrome pro- normally developed age-appropriated language9. It is charac- gresses as intractable seizures and further psychomotor delay3. terized by seizures and acquired aphasia, typically verbal au- West syndrome (WS) is characterized by developmental ditory agnosia, with onset
Load more
Loading...
Loading...
Loading...
Loading...
Loading...

8 pages remaining, click to load more.

Recommended publications
  • Epilepsy in Childhood
    Psychogenic Non-epileptic Seizures Dr Katharina Junejo Consultant Child and Adolescent Psychiatrist Aim Overview of basic principles in childhood epilepsy PNES Diagnosis of epilepsy Every child’s brain is capable of generating seizures with certain pro-convulsive drugs, acute metabolic disturbance, CNS infection, acute head trauma Risk of epilepsy after acute and provoked seizure is 3-5% Emotional stress is not considered provoking factor Henri Gastaut and colleagues proposed a classification of seizures: “all attempts at classification of seizures are hampered by our limited knowledge of the underlying pathological processes within the brain and that any classification must of necessity be a tentative one and will be subject to change with every advance in scientific understanding of epilepsy” (Gastaut et al 1964). Epilepsy has variable clinical presentations Convulsions (tonic- Staring spells clonic seizures) (absences) Period with confusion with or without Variants of automatism (complex paroxysmal events partial seizures) during sleep (common frontal lobe seizures) Limb or body jerk movements (myoclonus) Loss of speech/decline in Spasms (infantile or social, cognitive function Falls or drops epileptic spasms) (Landau-Kleffner (atonic but also syndrome) tonic seizures) ILAE Revised Terminology for Organization of Seizures and Epilepsies 2011 ‐ 2013 Classification of seizures: generalised and focal seizures Electroclinical syndromes and other epilepsies grouped by specificity of diagnosis (arranged by typical age of onset) Major conceptual changes: using aetiological classification of epilepsy-genetic, metabolic, immune, infectious and unknown causes Changes in terminology Operational diagnosis of epilepsy: occurrence of 2 or more unprovoked seizures, irrespective of seizure type (as recurrence risk is 80-90%) Careful history is only diagnostic test as many paroxysmal disorders that mimic epileptic seizures (most common vasovagal syncope or reflex anoxic seizure) Limitations of EEG: approx.
    [Show full text]
  • Prognostic Utility of Hypsarrhythmia Scoring in Children with West
    Clinical Neurology and Neurosurgery 184 (2019) 105402 Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Prognostic utility of hypsarrhythmia scoring in children with West syndrome T after ketogenic diet ⁎ Yunjian Zhang1, Lifei Yu1, Yuanfeng Zhou, Linmei Zhang, Yi Wang, Shuizhen Zhou Department of Pediatric Neurology, Children’s Hospital of Fudan University, China ARTICLE INFO ABSTRACT Keywords: Objective: The aim of this study was to evaluate the clinical efficacy and electroencephalographic (EEG) changes West syndrome of West syndrome after ketogenic diet (KD) therapy and to explore the correlation of EEG features and clinical Ketogenic diet efficacy. EEG Patients and methods: We retrospectively studied 39 patients with West syndrome who accepted KD therapy from Hypsarrhythmia May 2011 to October 2017. Outcomes including clinical efficacy and EEG features with hypsarrhythmia severity scores were analyzed. Results: After 3 months of treatment, 20 patients (51.3%) had ≥50% seizure reduction, including 4 patients (10.3%) who became seizure-free. After 6 months of treatment, 4 patients remained seizure free, 12 (30.8%) had 90–99% seizure reduction, 8 (20.5%) had a reduction of 50–89%, and 15 (38.5%) had < 50% reduction. Hypsarrhythmia scores were significantly decreased at 3 months of KD. They were associated with seizure outcomes at 6 months independent of gender, the course of disease and etiologies. Patients with a hypsar- rhythmia score ≥8 at 3 months of therapy may not be benefited from KD. Conclusion: Our findings suggest a potential benefit of KD for patients with drug-resistant West syndrome. Early change of EEG after KD may be a predictor of a patient’s response to the therapy.
    [Show full text]
  • Pediatric Disorders
    Neurological Disorder Part 3 - Pediatric Disorders CDKL5 Disorder • Characteristics: • Rare x-linked genetic disorder • CDLK5 mutations cause deficiencies in the protein needed for normal brain development • More common in females; however males with the disorder are affected much more severely than females © Trusted Neurodiagnostics Academy CDKL5 Disorder • Characteristics • CDKL5D mutations can be found in children who have been diagnosed with infantile spasms, Lennox Gastaut syndrome, Rett Syndrome, West Syndrome and autism © Trusted Neurodiagnostics Academy CDKL5 Disorder • Symptoms: • Infantile spasms beginning the first 3 - 6 months of life • Neurodevelopmental impairment • Patients cannot walk, talk, or feed themselves • Repetitive hand movements (stereotypies) © Trusted Neurodiagnostics Academy CDKL5 Disorder • Seizures: • Early onset • Infantile spasms, myoclonic, tonic, tonic-clonic seizures • Status epilepticus and non convulsive status epilepticus can occur © Trusted Neurodiagnostics Academy CDKL5 Disorder • Diagnosis: • Genetic blood testing to confirm the change or mutation on the CDKL5 gene • EEG © Trusted Neurodiagnostics Academy CDKL5 Disorder • EEG Findings: • Early in the disorder • EEG may be normal or slightly abnormal • During progression of the disorder • Some background activity is slow and epileptic discharges can be seen in one or more areas • Burst Suppression • Atypical hypsarrhythmia © Trusted Neurodiagnostics Academy CDKL5 Disorder © Trusted Neurodiagnostics Academy CDKL5 Disorder • Treatment: • Seizures
    [Show full text]
  • Levetiracetam-Associated Psychogenic Non-Epileptic Seizures
    Original Research DOI: 10.22374/1710-6222.25.2.1 LEVETIRACETAM-ASSOCIATED PSYCHOGENIC NON-EPILEPTIC SEIZURES: A HIDDEN PARADOX Shaik Afshan Jabeen,1 Padmaja Gaddamanugu,1 Ajith Cherian,2 Kandadai Rukmini Mridula,2 Dasari Uday Kumar,1 Angamuttu kanikannan Meena1 1Deptartment of Neurology Nizam’s Institute of Medical Sciences, Hyderabad, India. 2Department of Neurology, Sree Chitra Tirunal Institute of Medical Sciences. Thiruvananthapuram, India. Corresponding Author: drjabeennims@gmail.com Submitted: August 16, 2017. Accepted: May 31, 2018. Published: June 15, 2018. ABSTRACT Objectives To study the clinical profile and outcome in patients with epilepsy who developed psychogenic non-epileptic seizures (PNES) associated with levetiracetam (LEV) use. Methods In this prospective observational study, conducted over 1 year, 13 patients with epilepsy and PNES, docu- mented by video electroencephalogram (VEEG) while on LEV, were included. Those with past history of psychiatric illnesses were excluded. VEEG, high-resolution magnetic resonance imaging, neuropsychologi- cal and psychiatric evaluation were performed. Patients in Group I (07) were treated with psychotherapy, psychiatric medications and immediate withdrawal of LEV while, those in Group II (06) received psy- chotherapy, anxiolytics and LEV for initial 2 months after which it was stopped. Follow-up period was six months. Results Mean (±SD) age of patients was 25 ± 12.28 years; there were 11 (84.62%) females. All were on antiepileptic agents which included LEV >1000 mg/day, except one. Mean dose of LEV was 1269.23 ± 483.71 mg/day. J Popul Ther Clin Pharmacol Vol 25(2):1-11; June 15, 2018. This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License.
    [Show full text]
  • Outpatient Neurology Quick Reference Guide
    OCTOBER 1, 2015 Outpatient Neurology Quick Reference Guide Objective: Ensure your ICD-10 success by documenting at the required level on future orders. Limit the use of unspecified diagnosis codes; drive for specificity when anatomy, etiology, or severity is known. ICD-9 Codes ICD-10 Code Requirements for ICD-10 Success Produced from Order Equivalents of ICD-9 Codes Not Specific Specific 780.39: Convulsions R56.9: Unspecified convulsions Type of Convulsions: • Epileptic (coded as epilepsy) • Febrile • Jacksonian (coded as epilepsy) • Myoclonic • Neonatal • Obstetrical • Reflex • Other (coded as seizure) 345.90: Epilepsy, unspecified, without G40.909: Epilepsy, unspecified, not Type of Epilepsy: intractable epilepsy intractable, without status • Due to syphilis epileptus • Related to (e.g., alcohol, drugs, stress, etc.) • Localization-related • Generalized • Other Localization-related Epilepsy • Idiopathic or Symptomatic? • With seizures of localized onset? (idiopathic) • Complex partial seizures or simple partial seizures? (symptomatic) • Intractable? • With status epilepticus? Generalized Epilepsy • Idiopathic? • Intractable? • With status epilepticus? Please submit ICD-10 questions to icd10help@mhc.net. continued 11372 08/15 Copyright © 2015 Munson Healthcare, Traverse City, MI. All rights reserved. OCTOBER 1, 2015 Outpatient Neurology Quick Reference Guide Specific ICD-10-CM Codes Code Definition Convulsions R56.01 Complex febrile convulsions R53.00 Simple febrile convulsions G25.3 Myoclonus R25.8 Other abnormal involuntary movements
    [Show full text]
  • Investigation of Seizures in Infants
    Chapter 23 Investigation of seizures in infants RICHARD E. APPLETON1 and AILSA McLELLAN2 1The Roald Dahl EEG Unit, Paediatric Neurosciences Foundation, Alder Hey Children’s NHS Foundation Trust, Liverpool, and 2Department of Paediatric Neurosciences, Royal Hospital for Sick Children, Edinburgh The investigation of seizures in infancy (i.e. within the first year of life) begins with establishing whether the seizures are epileptic or non-epileptic in origin. The ‘broad’ differential diagnosis of possible seizures and ‘epilepsy’ is multiple and is particularly difficult under the age of 12 months and includes: Gastro-oesophageal reflux (Sandifer’s syndrome) Pallid syncopal attacks (reflex anoxic seizures) Cyanotic breath-holding attacks Cardiac arrhythmias Münchausen syndrome by proxy (passive or active both representing a form of child abuse) Shuddering spells and jitteriness Hyperekplexia Benign neonatal sleep myoclonus Benign myoclonus of infancy Tonic reflex activity and involuntary movements (seen in children with neurological impairment including cerebral palsy or hydrocephalus). Once a non-epileptic disorder has been excluded or the episodes are considered to be obviously epileptic, then the following conditions/investigations should be considered on a chronological basis. Perinatal (first week of life) and neonatal (first month of life) seizures The newborn period is the time of life with the highest risk of seizures1-3. This is because of the relative lack, and immature development of inhibitory neurotransmitters and their pathways. The immature and developing brain is susceptible to a large number of both cerebral and systemic insults including: Asphyxia (hypoxic-ischaemic encephalopathy) the most common and also most serious cause of neonatal seizures – particularly in term infants Intra- and periventricular haemorrhage – particularly in pre-term infants Metabolic dysfunction (e.g.
    [Show full text]
  • Genes of Early-Onset Epileptic Encephalopathies: from Genotype to Phenotype
    Pediatric Neurology 46 (2012) 24e31 Contents lists available at ScienceDirect Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu Review Article Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotype Mario Mastrangelo MD, Vincenzo Leuzzi MD * Division of Child Neurology, Department of Pediatrics, Child Neurology, and Psychiatry, Sapienza University of Rome, Rome, Italy article information abstract Article history: Early-onset epileptic encephalopathies are severe disorders in which cognitive, sensory, and motor Received 26 July 2011 development is impaired by recurrent clinical seizures or prominent interictal epileptiform discharges Accepted 24 October 2011 during the neonatal or early infantile periods. They include Ohtahara syndrome, early myoclonic epileptic encephalopathy, West syndrome, Dravet syndrome, and other diseases, e.g., X-linked myoclonic seizures, spasticity and intellectual disability syndrome, idiopathic infantile epileptic-dyskinetic encephalopathy, epilepsy and mental retardation limited to females, and severe infantile multifocal epilepsy. We summarize recent updates on the genes and related clinical syndromes involved in the pathogenesis of early-onset epileptic encephalopathies: Aristaless-related homeobox (ARX), cyclin- dependent kinase-like 5 (CDKL5), syntaxin-binding protein 1 (STXBP1), solute carrier family 25 member 22 (SLC25A22), nonerythrocytic a-spectrin-1 (SPTAN1), phospholipase Cb1(PLCb1), membrane- associated guanylate kinase inverted-2 (MAGI2), polynucleotide kinase
    [Show full text]
  • Infantile Spasms: an Update on Pre-Clinical Models and EEG Mechanisms
    children Review Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms Remi Janicot, Li-Rong Shao and Carl E. Stafstrom * Division of Pediatric Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; rjanico1@jhmi.edu (R.J.); lshao5@jhmi.edu (L.-R.S.) * Correspondence: cstafst1@jhmi.edu; Tel.: +1-(410)-955-4259; Fax: +1-(410)-614-2297 Received: 19 November 2019; Accepted: 23 December 2019; Published: 6 January 2020 Abstract: Infantile spasms (IS) is an epileptic encephalopathy with unique clinical and electrographic features, which affects children in the middle of the first year of life. The pathophysiology of IS remains incompletely understood, despite the heterogeneity of IS etiologies, more than 200 of which are known. In particular, the neurobiological basis of why multiple etiologies converge to a relatively similar clinical presentation has defied explanation. Treatment options for this form of epilepsy, which has been described as “catastrophic” because of the poor cognitive, developmental, and epileptic prognosis, are limited and not fully effective. Until the pathophysiology of IS is better clarified, novel treatments will not be forthcoming, and preclinical (animal) models are essential for advancing this knowledge. Here, we review preclinical IS models, update information regarding already existing models, describe some novel models, and discuss exciting new data that promises to advance understanding of the cellular mechanisms underlying the specific EEG changes seen in IS—interictal hypsarrhythmia and ictal electrodecrement. Keywords: infantile spasms; West syndrome; epilepsy; childhood; epileptic encephalopathy; electroencephalogram (EEG); hypsarrhythmia; electrodecrement; animal model 1. Introduction Epileptic encephalopathies (EEs) are a spectrum of disorders that mostly begin during infancy and have poor neurological and behavioral outcomes.
    [Show full text]
  • Epilepsy and Mitochondrial Dysfunction: ª the Author(S) 2017 DOI: 10.1177/2326409817733012 a Single Center’S Experience Journals.Sagepub.Com/Home/Iem
    Original Article Journal of Inborn Errors of Metabolism & Screening 2017, Volume 5: 1–12 Epilepsy and Mitochondrial Dysfunction: ª The Author(s) 2017 DOI: 10.1177/2326409817733012 A Single Center’s Experience journals.sagepub.com/home/iem Russell P. Saneto, DO, PhD1 Abstract Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n ¼ 180), over 48% of patients developed seizures. The majority (68%) of patients were younger than 3 years and medically intractable (90%). The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase g mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%). The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory. Keywords epilepsy, seizures, mitochondrial disease, electroencephalogram, infantile spasms, Alpers-Huttenlocher syndrome, status epilep- ticus, treatment Introduction wide variety of clinical phenotypes, including the high preva- lence of seizures and encephalopathy in mitochondrial diseases. Mitochondria are essential organelles involved in the proper Several studies have shown that approximately 35% to 60% of operation of the highly controlled cellular energetic processes individuals with biochemically confirmed mitochondrial disease of brain function, including amino acid and fatty acid synthesis 3–7 have epilepsy.
    [Show full text]
  • Epileptic Spasms in Clusters Without Hypsarrhythmia in Infancy
    Original article Epileptic Disord 2003; 5: 109-13 Epileptic spasms in clusters without hypsarrhythmia in infancy Roberto Horacio Caraballo1, Natalio Fejerman1, Bernardo Dalla Bernardina2, Victor Ruggieri1, Ricardo Cersósimo1, Carlos Medina3, Juan Pociecha3 1. Servicio de Neurología, Hospital de Niños “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina. 2. Neuropediatric Department, Borgo Roma Hospital, University of Verona, Italy. 3. Servicio de Neurofisiología, Hospital de Niños “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina. Received December 31, 2002; Accepted April 25, 2003 ABSTRACT − Spasms are defined as epileptic seizures characterized by brief axial contraction, in flexion, extension or mixed, symmetric or asymmetric, lasting from a fraction of a second to 1-2s, and are associated with a slow-wave transient or sharp and slow-wave complex, followed or not by voltage attenu- ation. Epileptic spasms usually appear in clusters and are age-dependent. This type of epileptic spasms associated with the particular EEG pattern, hypsar- rhythmia, constitutes the basis for the diagnosis of West syndrome. The question is, how to nosologically define those patients who clearly present epileptic spasms in clusters without modified or typical hypsarrhythmia and with or without focal paroxysmal discharges on the interictal EEG. In the present series, the four patients show that epileptic spasms in clusters may occur in infancy, without hypsarrhythmia. They all presented the following features: normal neuropsychological development before onset of epileptic spasms, clusters of epileptic spasms, focal clinical and/or EEG abnormalities, normal neuroradiological imaging, neurometabolic investigations and karyotypes. In three of the patients, seizures were refractory to AEDs. Epileptic spasms in clusters without hypsarrhythmia that start in the first year of life represent a subtype of infantile spasms that generally are refractory to AEDs.
    [Show full text]
  • Temporal Lobe Epilepsy Semiology
    Hindawi Publishing Corporation Epilepsy Research and Treatment Volume 2012, Article ID 751510, 10 pages doi:10.1155/2012/751510 Review Article Temporal Lobe Epilepsy Semiology Robert D. G. Blair Division of Neurology, Department of Medicine, Credit Valley Hospital, University of Toronto, Mississauga, ON, Canada L5M 2N1 Correspondence should be addressed to Robert D. G. Blair, rdgblair@mac.com Received 22 October 2011; Accepted 26 December 2011 Academic Editor: Seyed M. Mirsattari Copyright © 2012 Robert D. G. Blair. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone.
    [Show full text]
  • Pediatric Epilepsy
    PEDIATRIC EPILEPSY Ø Epilepsy is one of the most common chronic neurological disorders. It is characterized by recurrent unprovoked seizures or an enduring predisposition to generate epileptic seizures. If epilepsy begins in childhood, it is often outgrown. Seizures are common in childhood and adolescence. Approximately 3% of children will experience a seizure. Ø A seizure occurs when there is a sudden change in behavior or sensation caused by abnormal and excessive electrical hypersynchronization of neuronal networks in the cerebral cortex. Normal inhibition is overcome by excessive excitatory stimuli. Ø If the cause of the seizures is known (for example: genetic, inborn errors of metabolism, metabolic (eg: low glucose, electrolyte abnormalities), structural (eg: malformations, tumours, bleeds, stroke, traumatic brain injury), infectious, inflammatory, or toxins) it is classified as symptomatic. If the cause is unknown, it is classified as idiopathic. 1. WHERE DID THE SEIZURE START? / WHAT KIND OF SEIZURE IS IT? 2. IS AWARENESS YES FOCAL ONSET GENERALIZED UNKNOWN IMPAIRED? NO Seizure that originates ONSET ONSET in a focal cortical area Seizure that involves When it is unclear YES with associated clinical both sides of the where the seizure 3. PROGRESSION TO BILATERAL? features. brain from the onset. starts. NO SEIZURE SEMIOLOGY (The terminology for seizure types is designed to be useful for communicating the key characteristics of seizures) CLONIC: sustained rhythmical TONIC: muscles stiffen or ATONIC: sudden loss of muscle tone, MYOCLONUS: sudden lighting- jerking movements. tense. lasting seconds. like jerk, may cluster. EPILEPTIC SPASM: sudden AUTONOMIC: eg: AUTOMATISMS: ABSENCE: brief (≤ 10s), OTHERS: change flexion, extension, or flexion- rising epigastric stereotyped, purposeless frequent (up to 100’s) in cognition, extension of proximal and sensations, waves of movements.
    [Show full text]