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Epileptic encephalopathy

Last edited: 4/14/2026

Overview

Epileptic encephalopathies are severe neurological disorders characterized by early-onset seizures, pharmacoresistant epilepsy, and significant cognitive decline or developmental regression 10. These conditions often manifest with specific electroencephalography (EEG) patterns, such as suppression-burst in Ohtahara syndrome, and can be caused by genetic mutations affecting various cellular functions including metabolism, ion channels, and neuronal development 11624.

Diagnosis

  • Clinical Presentation: Early onset of seizures, developmental delay, and characteristic EEG patterns (e.g., suppression-burst in Ohtahara syndrome, multifocal spikes in Dravet syndrome) 121824.
  • Genetic Testing: Sequencing of candidate genes (e.g., SLC13A5, SCN1A, AP3B2, CDK19, ITPA, BRAT1, ARX, STXBP1) to identify causative mutations 14671116.
  • Neuroimaging: MRI to identify structural abnormalities (e.g., focal cortical dysplasia, migrational disorders) 2223.
  • Metabolic Screening: Blood and urine tests for inborn errors of metabolism (e.g., PNPO deficiency) 917.

    • Management

  • First-Line Treatments:
    • - Antiepileptic Drugs (AEDs): Phenobarbital, valproate, levetiracetam (specific dosing varies; consult individual guidelines) 10.
  • Adjunctive Therapies:
    • - Pyridoxal 5'-Phosphate (PLP): For PNPO deficiency, early treatment can be curative 17. - Chloral Hydrate: May provide symptomatic relief in Ohtahara syndrome 20. - Surgical Intervention: Consider for focal structural abnormalities identified by neuroimaging 22.

    Special Populations

  • Pediatrics: Early genetic testing and metabolic screening are crucial for timely diagnosis and intervention 1917.
  • Comorbidities: Management should consider coexisting metabolic disorders and structural brain anomalies, tailoring treatment to address multiple facets of the condition 92223.

    • Key Recommendations

  • Genetic Testing for Early Diagnosis: Implement comprehensive genetic testing early in the diagnostic process to identify specific mutations (e.g., SLC13A5, SCN1A) 1671116 (Evidence: Strong).
  • Early Metabolic Screening: Screen for inborn errors of metabolism, particularly PNPO deficiency, in neonates presenting with epileptic encephalopathy 917 (Evidence: Moderate).
  • Consider Surgical Options: Evaluate surgical intervention for patients with focal cortical dysplasia or other identifiable structural brain anomalies 22 (Evidence: Expert opinion).
  • Tailored Pharmacological Approaches: Use a combination of AEDs and consider adjunctive therapies like PLP for metabolic deficiencies 1017 (Evidence: Moderate).

    • References

    1 Alsemari A, Guzmán-Vega FJ, Meyer BF, Arold ST. Novel Homozygous Variants of SLC13A5 Expand the Functional Heterogeneity of a Homogeneous Syndrome of Early Infantile Epileptic Encephalopathy. Pediatric neurology 2024. link 2 Minato E, Myers KA. Age-related evolution of EEG in Dravet syndrome: Meta-analysis of 155 patients. Seizure 2021. link 3 Inuzuka LM, Macedo-Souza LI, Della-Rippa B, Monteiro FP, Delgado DS, Godoy LF et al.. ATP6V1B2-related epileptic encephalopathy. Epileptic disorders : international epilepsy journal with videotape 2020. link 4 Chung HL, Mao X, Wang H, Park YJ, Marcogliese PC, Rosenfeld JA et al.. De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy. American journal of human genetics 2020. link 5 Sakamoto M, Kouhei D, Haniffa M, Silva S, Troncoso M, Santander P et al.. A novel ITPA variant causes epileptic encephalopathy with multiple-organ dysfunction. Journal of human genetics 2020. link 6 Assoum M, Philippe C, Isidor B, Perrin L, Makrythanasis P, Sondheimer N et al.. Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. American journal of human genetics 2016. link 7 Straussberg R, Ganelin-Cohen E, Goldberg-Stern H, Tzur S, Behar DM, Smirin-Yosef P et al.. Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2015. link 8 Simons C, Griffin LB, Helman G, Golas G, Pizzino A, Bloom M et al.. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. American journal of human genetics 2015. link 9 Ware TL, Earl J, Salomons GS, Struys EA, Peters HL, Howell KB et al.. Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment. Developmental medicine and child neurology 2014. link 10 Covanis A. Epileptic encephalopathies (including severe epilepsy syndromes). Epilepsia 2012. link 11 Milh M, Villeneuve N, Chouchane M, Kaminska A, Laroche C, Barthez MA et al.. Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. Epilepsia 2011. link 12 Giordano L, Sartori S, Russo S, Accorsi P, Galli J, Tiberti A et al.. Familial Ohtahara syndrome due to a novel ARX gene mutation. American journal of medical genetics. Part A 2010. link 13 Molinari F. Mitochondria and neonatal epileptic encephalopathies with suppression burst. Journal of bioenergetics and biomembranes 2010. link 14 Jocic-Jakubi B, Lagae L. Malignant migrating partial seizures in Aicardi syndrome. Developmental medicine and child neurology 2008. link 15 Kobayashi K, Inoue T, Kikumoto K, Endoh F, Miya K, Oka M et al.. Relation of spasms and myoclonus to suppression-burst on EEG in epileptic encephalopathy in early infancy. Neuropediatrics 2007. link 16 Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M et al.. A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). American journal of human genetics 2007. link 17 Hoffmann GF, Schmitt B, Windfuhr M, Wagner N, Strehl H, Bagci S et al.. Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy. Journal of inherited metabolic disease 2007. link 18 Ohtahara S, Yamatogi Y. Epileptic encephalopathies in early infancy with suppression-burst. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2003. link 19 Guerrini R, Aicardi J. Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy). Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2003. link 20 Krsek P, Sebronová V, Procházka T, Maulisová A, Komárek V. Successful treatment of Ohtahara syndrome with chloral hydrate. Pediatric neurology 2002. link00464-2) 21 Trinka E, Rauscher C, Nagler M, Moroder T, Ladurner G, Irnberger E et al.. A case of Ohtahara syndrome with olivary-dentate dysplasia and agenesis of mamillary bodies. Epilepsia 2001. link 22 Komaki H, Sugai K, Sasaki M, Hashimoto T, Arai N, Takada E et al.. Surgical treatment of a case of early infantile epileptic encephalopathy with suppression-bursts associated with focal cortical dysplasia. Epilepsia 1999. link 23 Miller SP, Dilenge ME, Meagher-Villemure K, O'Gorman AM, Shevell MI. Infantile epileptic encephalopathy (Ohtahara syndrome) and migrational disorder. Pediatric neurology 1998. link00009-5) 24 Ohtahara S, Ohtsuka Y, Oka E. Epileptic encephalopathies in early infancy. Indian journal of pediatrics 1997. link 25 Clarke M, Gill J, Noronha M, McKinlay I. Early infantile epileptic encephalopathy with suppression burst: Ohtahara syndrome. Developmental medicine and child neurology 1987. link 26 Dóra E, Kovách AG. Regulation of cerebral blood flow (CBF) during hypoxia and epileptic seizures. Advances in experimental medicine and biology 1985. link

    Original source

    1. [1]
      Novel Homozygous Variants of SLC13A5 Expand the Functional Heterogeneity of a Homogeneous Syndrome of Early Infantile Epileptic Encephalopathy. — Alsemari A, Guzmán-Vega FJ, Meyer BF, Arold ST Pediatric neurology (2024)
    2. [2]
      Age-related evolution of EEG in Dravet syndrome: Meta-analysis of 155 patients. — Minato E, Myers KA Seizure (2021)
    3. [3]
      ATP6V1B2-related epileptic encephalopathy. — Inuzuka LM, Macedo-Souza LI, Della-Rippa B, Monteiro FP, Delgado DS, Godoy LF et al. Epileptic disorders : international epilepsy journal with videotape (2020)
    4. [4]
      De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy. — Chung HL, Mao X, Wang H, Park YJ, Marcogliese PC, Rosenfeld JA et al. American journal of human genetics (2020)
    5. [5]
      A novel ITPA variant causes epileptic encephalopathy with multiple-organ dysfunction. — Sakamoto M, Kouhei D, Haniffa M, Silva S, Troncoso M, Santander P et al. Journal of human genetics (2020)
    6. [6]
      Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. — Assoum M, Philippe C, Isidor B, Perrin L, Makrythanasis P, Sondheimer N et al. American journal of human genetics (2016)
    7. [7]
      Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation. — Straussberg R, Ganelin-Cohen E, Goldberg-Stern H, Tzur S, Behar DM, Smirin-Yosef P et al. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society (2015)
    8. [8]
      Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. — Simons C, Griffin LB, Helman G, Golas G, Pizzino A, Bloom M et al. American journal of human genetics (2015)
    9. [9]
      Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment. — Ware TL, Earl J, Salomons GS, Struys EA, Peters HL, Howell KB et al. Developmental medicine and child neurology (2014)
    10. [10]
      Epileptic encephalopathies (including severe epilepsy syndromes). — Covanis A Epilepsia (2012)
    11. [11]
      Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations. — Milh M, Villeneuve N, Chouchane M, Kaminska A, Laroche C, Barthez MA et al. Epilepsia (2011)
    12. [12]
      Familial Ohtahara syndrome due to a novel ARX gene mutation. — Giordano L, Sartori S, Russo S, Accorsi P, Galli J, Tiberti A et al. American journal of medical genetics. Part A (2010)
    13. [13]
      Mitochondria and neonatal epileptic encephalopathies with suppression burst. — Molinari F Journal of bioenergetics and biomembranes (2010)
    14. [14]
      Malignant migrating partial seizures in Aicardi syndrome. — Jocic-Jakubi B, Lagae L Developmental medicine and child neurology (2008)
    15. [15]
      Relation of spasms and myoclonus to suppression-burst on EEG in epileptic encephalopathy in early infancy. — Kobayashi K, Inoue T, Kikumoto K, Endoh F, Miya K, Oka M et al. Neuropediatrics (2007)
    16. [16]
      A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). — Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M et al. American journal of human genetics (2007)
    17. [17]
      Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy. — Hoffmann GF, Schmitt B, Windfuhr M, Wagner N, Strehl H, Bagci S et al. Journal of inherited metabolic disease (2007)
    18. [18]
      Epileptic encephalopathies in early infancy with suppression-burst. — Ohtahara S, Yamatogi Y Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society (2003)
    19. [19]
      Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy). — Guerrini R, Aicardi J Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society (2003)
    20. [20]
      Successful treatment of Ohtahara syndrome with chloral hydrate. — Krsek P, Sebronová V, Procházka T, Maulisová A, Komárek V Pediatric neurology (2002)
    21. [21]
      A case of Ohtahara syndrome with olivary-dentate dysplasia and agenesis of mamillary bodies. — Trinka E, Rauscher C, Nagler M, Moroder T, Ladurner G, Irnberger E et al. Epilepsia (2001)
    22. [22]
      Surgical treatment of a case of early infantile epileptic encephalopathy with suppression-bursts associated with focal cortical dysplasia. — Komaki H, Sugai K, Sasaki M, Hashimoto T, Arai N, Takada E et al. Epilepsia (1999)
    23. [23]
      Infantile epileptic encephalopathy (Ohtahara syndrome) and migrational disorder. — Miller SP, Dilenge ME, Meagher-Villemure K, O'Gorman AM, Shevell MI Pediatric neurology (1998)
    24. [24]
      Epileptic encephalopathies in early infancy. — Ohtahara S, Ohtsuka Y, Oka E Indian journal of pediatrics (1997)
    25. [25]
      Early infantile epileptic encephalopathy with suppression burst: Ohtahara syndrome. — Clarke M, Gill J, Noronha M, McKinlay I Developmental medicine and child neurology (1987)
    26. [26]
      Regulation of cerebral blood flow (CBF) during hypoxia and epileptic seizures. — Dóra E, Kovách AG Advances in experimental medicine and biology (1985)
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