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Revista de Neurologia May 2017Epileptic encephalopathies in infancy are defined as conditions where the sustained epileptic activity itself may contribute to the severe neurological and cognitive... (Review)
Review
INTRODUCTION
Epileptic encephalopathies in infancy are defined as conditions where the sustained epileptic activity itself may contribute to the severe neurological and cognitive impairment. These epileptic encephalopathies include Ohtahara syndrome, early myoclonic epileptic encephalopathy, West syndrome, Dravet syndrome, and malignant migrating epilepsy in infancy. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects.
AIM
To present and discuss current knowledge regarding genetic findings in epileptic encephalopathies in infancy, phenotype-genotype correlations in different forms of paediatric epileptic encephalopathies, and the impact of these new findings in clinical practice.
DEVELOPMENT
Patients with unclear etiologies after performing a brain magnetic resonance imaging should be considered for a further workup, which should include an evaluation for genetic defects. Nowadays, more than 50 genes have been associated with epileptic encephalopathies in infancy. Targeted next-generation sequencing panels show a high diagnostic yield in patients with epileptic encephalopathies.
CONCLUSIONS
Genetic knowledge about epileptic encephalopathies in infancy has revolutionized the diagnostic approach to these disorders, and an increasing number of gene mutations have been related to their pathogenesis. A more detailed classification of epileptic encephalopathies genotypes will improve the accuracy of genotype-phenotype correlation and genetic counseling. All these developments could yield therapeutic applications such as gene therapy or antiepileptic drugs 'tailored' to the specific genetic markers or targets.
Topics: Brain Diseases, Metabolic, Inborn; Child, Preschool; Drug Resistant Epilepsy; Electroencephalography; Epileptic Syndromes; Genetic Association Studies; Genetic Techniques; Heredodegenerative Disorders, Nervous System; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Malformations of Cortical Development; Neuroimaging; Spasms, Infantile
PubMed: 28524223
DOI: No ID Found -
Cleveland Clinic Journal of Medicine 1989
Review
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Humans; Infant; Pyridoxine; Spasms, Infantile
PubMed: 2541944
DOI: No ID Found -
Revista de Neurologia Sep 2013This study describes the clinical and electroencephalographic characteristics of epileptic spasms, and more especially those that occur during the first two years of... (Review)
Review
This study describes the clinical and electroencephalographic characteristics of epileptic spasms, and more especially those that occur during the first two years of life (infantile spasms). West syndrome has been clearly defined as the association between infantile spasms with an electroencephalographic pattern of hypsarrhythmia. Although intellectual deficit appears in almost all cases in which infantile spasms are not controlled with medication, this is a developmental aspect of the condition and not a manifestation that must necessarily be present in order to define the syndrome. The analysis of the interictal and ictal electroencephalogram readings, together with the clinical characteristics of the spasms and the neurological examination of patients, provides some orientation as regards the causations. Despite the spectrum that the title of this work focuses on, the study does not cover the treatment of early infants with West syndrome. Emphasis is placed on the differential diagnoses of West syndrome with other epileptic syndromes that manifest in the first two years of life, and more especially with a series of abnormal non-epileptic motor phenomena that occur in early infants. All these last non-epileptic disorders are displayed in a table, but benign myoclonus of early infancy or Fejerman syndrome is given as a paradigmatic example for the differential diagnosis. The primordial aim is to prevent neurologically healthy early infants from receiving antiepileptic drugs and even adrenocorticotropic hormone or corticoids due to a mistaken diagnosis.
Topics: Age of Onset; Brain Diseases; Child, Preschool; Diagnosis, Differential; Dyskinesias; Dystonia; Electroencephalography; Epilepsy, Benign Neonatal; Humans; Infant; Myoclonus; Parasomnias; Spasms, Infantile
PubMed: 23897139
DOI: No ID Found -
Neurotherapeutics : the Journal of the... Oct 2014Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy,... (Review)
Review
Epileptic encephalopathies represent a group of devastating epileptic disorders that occur early in life and are often characterized by pharmaco-resistant epilepsy, persistent severe electroencephalographic abnormalities, and cognitive dysfunction or decline. Next generation sequencing technologies have increased the speed of gene discovery tremendously. Whereas ion channel genes were long considered to be the only significant group of genes implicated in the genetic epilepsies, a growing number of non-ion-channel genes are now being identified. As a subgroup of the genetically mediated epilepsies, epileptic encephalopathies are complex and heterogeneous disorders, making diagnosis and treatment decisions difficult. Recent exome sequencing data suggest that mutations causing epileptic encephalopathies are often sporadic, typically resulting from de novo dominant mutations in a single autosomal gene, although inherited autosomal recessive and X-linked forms also exist. In this review we provide a summary of the key features of several early- and mid-childhood onset epileptic encephalopathies including Ohtahara syndrome, Dravet syndrome, Infantile spasms and Lennox Gastaut syndrome. We review the recent next generation sequencing findings that may impact treatment choices. We also describe the use of conventional and newer anti-epileptic and hormonal medications in the various syndromes based on their genetic profile. At a biological level, developments in cellular reprogramming and genome editing represent a new direction in modeling these pediatric epilepsies and could be used in the development of novel and repurposed therapies.
Topics: Brain; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Infant, Newborn; Landau-Kleffner Syndrome; Lennox Gastaut Syndrome; Sequence Analysis, DNA; Spasms, Infantile
PubMed: 25266964
DOI: 10.1007/s13311-014-0301-2 -
Indian Pediatrics Jul 2008To assess the seizure and developmental outcome in children with West syndrome with respect to treatment lag.
OBJECTIVES
To assess the seizure and developmental outcome in children with West syndrome with respect to treatment lag.
METHODS
Twenty-six children satisfying inclusion criteria of West syndrome i.e., infantile spasms, psychomotor retardation and abnormal EEG pattern were prospectively evaluated. Response to treatment was assessed based on seizure control, EEG, developmental assessment and parental observations.
RESULTS
The time lag from onset of seizures to appropriate treatment was <1 month in 11 children; 1-6 months in 8 children; and >6 months in 7 children. Children with treatment lag <1 month fared better than those who had a large treatment lag (P<0.05). Children with good seizure control also showed better developmental improvement (P<0.05).
CONCLUSION
Children with West syndrome have better seizure control and development, if the treatment is started within 1 month of onset of symptoms.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Brain; Child, Preschool; Cognition Disorders; Electroencephalography; Female; Humans; Infant; Male; Neuropsychological Tests; Prospective Studies; Severity of Illness Index; Spasms, Infantile; Valproic Acid
PubMed: 18695274
DOI: No ID Found -
Tidsskrift For Den Norske Laegeforening... Jan 2011Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy, which starts in childhood with various seizure types. The children develop cognitive impairment and a... (Review)
Review
BACKGROUND
Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy, which starts in childhood with various seizure types. The children develop cognitive impairment and a typical EEG pattern. The aim of this article is to describe the clinical presentation of LGS, with particular emphasis on the course in adulthood.
MATERIAL AND METHODS
The article is based on literature (up to November 2009) identified through a non-systematic search in PubMed and our own clinical experience.
RESULTS
There are cases with unknown etiology and symptomatic cases with a wide spectrum of etiologies. While children with LGS have a high frequency of generalized seizures, seizure activity tends to decrease somewhat in adulthood and the seizures may become more focal. The prognosis is usually poor. The adult patient with LGS is clearly affected by global encephalopathy and is typically characterized by bluntness, apathy, progressive cognitive failure and motoric deficits. Valproate has been the first-line treatment for many years, but newer antiepileptic drugs; such as lamotrigine, topiramate and rufinamide, have shown efficacy as add-on therapy. Overtreatment with antiepileptic drugs is common.
INTERPRETATION
For optimal treatment, a specialist should follow LGS patients at all ages. New treatment options with milder side effects may improve the quality of life for these patients.
Topics: Adult; Anticonvulsants; Diagnosis, Differential; Electroencephalography; Humans; Intellectual Disability; Lennox Gastaut Syndrome; Prognosis; Quality of Life; Spasms, Infantile
PubMed: 21233883
DOI: 10.4045/tidsskr.09.1540 -
Indian Journal of Pediatrics Aug 2021
Topics: Adrenocorticotropic Hormone; Humans; Pharmaceutical Preparations; Spasms, Infantile
PubMed: 33772432
DOI: 10.1007/s12098-021-03747-z -
Indian Pediatrics Jan 2021West syndrome is one of the commonest causes of epilepsy in infants and young children and is a significant contributor to neurodevelopmental morbidity. Multiple...
JUSTIFICATION
West syndrome is one of the commonest causes of epilepsy in infants and young children and is a significant contributor to neurodevelopmental morbidity. Multiple regimens for treatment are in use.
PROCESS
An expert group consisting of pediatric neurologists and epileptologists was constituted. Experts were divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed a consensus. The evidence was reviewed, and for areas where the evidence was not certain, the Delphi consensus method was adopted. The final guidelines were circulated to all experts for approval.
RECOMMENDATIONS
Diagnosis should be based on clinical recognition (history/home video recordings) of spasms and presence of hypsarrhythmia or its variants on electroencephalography. A magnetic resonance imaging of the brain is the preferred neuroimaging modality. Other investigations such as genetic and metabolic testing should be planned as per clinico-radiological findings. Hormonal therapy (adrenocorticotropic hormone or oral steroids) should be preferred for cases other than tuberous sclerosis complex and vigabatrin should be the first choice for tuberous sclerosis complex. Both ACTH and high dose prednisolone have reasonably similar efficacy and adverse effect profile for West syndrome. The choice depends on the preference of the treating physician and the family, based on factors of cost, availability of infrastructure and personnel for daily intramuscular injections, and monitoring side effects. Second line treatment options include anti-epileptic drugs (vigabatrin, sodium valproate, topiramate, zonisamide, nitrazepam and clobazam), ketogenic diet and epilepsy surgery.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Child; Child, Preschool; Epilepsy; Humans; Infant; Neurology; Spasms, Infantile
PubMed: 33452776
DOI: No ID Found -
Developmental Medicine and Child... Nov 2019
Topics: Child; Humans; Spasms, Infantile
PubMed: 30945274
DOI: 10.1111/dmcn.14236 -
Anales de Pediatria Sep 2018West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. (Observational Study)
Observational Study
INTRODUCTION
West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin.
OBJECTIVES
To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors.
PATIENTS AND METHODS
The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years.
RESULTS
The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis.
CONCLUSIONS
The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH.
Topics: Female; Humans; Infant; Male; Prognosis; Retrospective Studies; Spasms, Infantile; Treatment Outcome
PubMed: 29223473
DOI: 10.1016/j.anpedi.2017.10.012