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Epileptic Encephalopathies as Neurodegenerative Disorders

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Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 15))

Abstract

The epileptic encephalopathies are severe and often treatment-resistant conditions that are associated with a progressive disturbance of brain function, resulting in a broad range of neurological and non-neurological comorbidities. The concept of epileptic encephalopathies entails that the encephalopathy aspect of the overall condition is primarily driven by the epileptic activity of the disease, which often manifests as specific and pathological features on the electroencephalogram. Genetic factors in epileptic encephalopathies are increasingly recognized. As of 2016, more than 30 genes have been securely implicated as causative genes for genetic epileptic encephalopathies. Even though the traditional concept of epileptic encephalopathies entails that the progressive disturbance of brain dysfunction is primarily due to the abnormal hypersynchronous activity that underlies the seizure disorders, this strict concept rarely holds true for patients with identified genetic etiologies. More commonly, an underlying genetic etiology is thought to predispose both to the neurodevelopmental comorbidities and to the seizure phenotype with a complex interaction between both. In this chapter, we will elucidate to what extent neurodegeneration rather than epilepsy-related regression is a feature of the common epileptic encephalopathies, drawing parallels between two relatively separate fields of neurogenetic research.

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Abbreviations

ACC:

Agenesis of the corpus callosum

CA1/CA3:

Cornu Ammonis 1/3

CNS:

Central nervous system

CSWS:

Continuous spike-wave activity in slow-wave sleep

EEG:

Electroencephalography

FTD:

Frontotemporal dementia

GABA:

Gamma-aminobutyric acid

GGE:

Genetic generalized epilepsy

GSW:

Generalized spike-wave

HSP:

Hereditary spastic paraplegia

hyperKPP:

Hyperkalemic periodic paralysis

IGE:

Idiopathic generalized epilepsy

INAD:

Infantile neuroaxonal dystrophy

iPSCs:

Induced pluripotent stem cells

iPSP:

Inhibitory postsynaptic potential

JAE:

Juvenile absence epilepsy

JME:

Juvenile myoclonic epilepsy

MRI:

Magnetic resonance imaging

mRNA:

Messenger ribonucleic acid

NBIA:

Neurodegeneration with brain iron accumulation

NCL:

Neuronal ceroid lipofuscinosis

PKAN:

Pantothenate kinase-associated neurodegeneration

PME:

Progressive myoclonus epilepsy

SENDA:

Static encephalopathy with neurodegeneration in adulthood

ULD:

Unverricht-Lundborg disease

XLAG:

X-linked lissencephaly with abnormal genitalia

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Author information

Authors and Affiliations

  1. Division of Child Neurology, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Ingo Helbig M.D., Markus von Deimling cand. med. & Eric D. Marsh M.D., Ph.D.

  2. Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany

    Ingo Helbig M.D. & Markus von Deimling cand. med.

  3. Division of Genomic Diagnostics, Department of Pathology, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Ingo Helbig M.D.

  4. Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Eric D. Marsh M.D., Ph.D.

  5. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 34th St and Civic Center Blvd, Philadelphia, PA, 19104, USA

    Eric D. Marsh M.D., Ph.D.

Authors
  1. Ingo Helbig M.D.
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  2. Markus von Deimling cand. med.
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  3. Eric D. Marsh M.D., Ph.D.
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Corresponding author

Correspondence to Eric D. Marsh M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. University of Melbourne Florey Institute of Neuroscience and Mental Health, Parkville, Australia

    Philip Beart

  2. Pediatrics and Pharmacology Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Michael Robinson

  3. School of Life Sciences Bradford School of Pharmacy, University of Bradford, Bradford, United Kingdom

    Marcus Rattray

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Nicholas J. Maragakis

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Helbig, I., von Deimling, M., Marsh, E.D. (2017). Epileptic Encephalopathies as Neurodegenerative Disorders. In: Beart, P., Robinson, M., Rattray, M., Maragakis, N. (eds) Neurodegenerative Diseases. Advances in Neurobiology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-57193-5_11

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