Skip to main content
Log in

Current Treatment Options for Early-Onset Pediatric Epileptic Encephalopathies

  • Pediatric Neurology (R-M Boustany, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

The management of early-onset, genetically determined epilepsies is often challenging. First-line anti-epileptic drugs (AEDs) often include phenobarbital, phenytoin, oxcarbazepine, carbamazepine, clonazepam, levetiracetam, and valproic acid. Combinations of medications are used in these patients with often intractable seizures, and they include topiramate, clobazam, felbamate, lacosamide, lamotrigine, rufinamide, vigabatrin, ACTH, oral steroids, and the ketogenic diet. Vagus nerve stimulator therapy offers some relief in selected patients. Surgical procedures, such as multiple subpial transections (MSTs), hemispherectomy, focal epilepsy surgery, or corpus callosotomy, may also be performed in selected patients. Careful monitoring of drug levels, if available, is highly recommended, as well as liver function tests, complete blood count, and electrolyte levels. AEDs often interact with each other, and the physician must be knowledgeable about such drug interactions, when selecting a new medication. In this article, the various encephalopathies are reviewed and presented according to age of onset of symptoms. Different treatment options are also summarized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Engel Jr J, E. International League Against. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42(6):796–803.

    Article  PubMed  Google Scholar 

  2. Rodgers WP et al. Interrater reliability of Engel, International League Against Epilepsy, and McHugh seizure outcome classifications following vagus nerve stimulator implantation. J Neurosurg Pediatr. 2012;10(3):226–9.

    Article  PubMed  Google Scholar 

  3. Ohtahara S, Yamatogi Y. Epileptic encephalopathies in early infancy with suppression-burst. J Clin Neurophysiol. 2003;20(6):398–407.

    Article  PubMed  Google Scholar 

  4. Pavone P et al. Ohtahara syndrome with emphasis on recent genetic discovery. Brain Dev. 2012;34(6):459–68.

    Article  PubMed  Google Scholar 

  5. Singhi P, Ray M. Ohtahara syndrome with biotinidase deficiency. J Child Neurol. 2011;26(4):507–9.

    Article  PubMed  Google Scholar 

  6. Deprez L et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010;75(13):1159–65.

    Article  CAS  PubMed  Google Scholar 

  7. Kato M et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia. 2013;54(7):1282–7. This article highlights an important genetic mutation and its spectrum as a cause of Ohtahara syndrome.

    Article  CAS  PubMed  Google Scholar 

  8. Saitsu H et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia. 2010;51(12):2397–405.

    Article  CAS  PubMed  Google Scholar 

  9. Nakamura K et al. Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome. Neurology. 2013;81(11):992–8.

    Article  CAS  PubMed  Google Scholar 

  10. Kodera H et al. De novo GABRA1 mutations in Ohtahara and West syndromes. Epilepsia. 2016;57:566–73.

    Article  CAS  PubMed  Google Scholar 

  11. Wilmshurst JM et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015;56(8):1185–97. This article summarizes the major up-to-date recommendations for treatment of early-onset epileptic encephalopathies.

    Article  PubMed  Google Scholar 

  12. Tso WW et al. Folinic acid responsive epilepsy in Ohtahara syndrome caused by STXBP1 mutation. Pediatr Neurol. 2014;50(2):177–80.

    Article  PubMed  Google Scholar 

  13. Mastrangelo M, Celato A, Leuzzi V. A diagnostic algorithm for the evaluation of early onset genetic-metabolic epileptic encephalopathies. Eur J Paediatr Neurol. 2012;16(2):179–91.

    Article  PubMed  Google Scholar 

  14. Cohen R et al. Two siblings with early infantile myoclonic encephalopathy due to mutation in the gene encoding mitochondrial glutamate/H+ symporter SLC25A22. Eur J Paediatr Neurol. 2014;18(6):801–5.

    Article  PubMed  Google Scholar 

  15. McTague A, Cross JH. Treatment of epileptic encephalopathies. CNS Drugs. 2013;27(3):175–84. This article presents a variety of different treatments for epileptic encephalopathies and a clinical summary for each type of genetic epilepsy.

    Article  CAS  PubMed  Google Scholar 

  16. Coppola G et al. Migrating partial seizures in infancy: a malignant disorder with developmental arrest. Epilepsia. 1995;36(10):1017–24.

    Article  CAS  PubMed  Google Scholar 

  17. Nabbout R, Dulac O. Epileptic encephalopathies: a brief overview. J Clin Neurophysiol. 2003;20(6):393–7.

    Article  PubMed  Google Scholar 

  18. Coppola G. Malignant migrating partial seizures in infancy. Handb Clin Neurol. 2013;111:605–9.

    Article  PubMed  Google Scholar 

  19. Barcia G et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012;44(11):1255–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Poduri A et al. SLC25A22 is a novel gene for migrating partial seizures in infancy. Ann Neurol. 2013;74(6):873–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ohba C et al. De novo KCNT1 mutations in early-onset epileptic encephalopathy. Epilepsia. 2015;56(9):e121–8.

    CAS  PubMed  Google Scholar 

  22. Caraballo R et al. Epilepsy of infancy with migrating focal seizures: six patients treated with bromide. Seizure. 2014;23(10):899–902.

    Article  PubMed  Google Scholar 

  23. Gerard F et al. Focal seizures versus focal epilepsy in infancy: a challenging distinction. Epileptic Disord. 1999;1(2):135–9.

    CAS  PubMed  Google Scholar 

  24. Perez J et al. Stiripentol: efficacy and tolerability in children with epilepsy. Epilepsia. 1999;40(11):1618–26.

    Article  CAS  PubMed  Google Scholar 

  25. Cilio MR et al. Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy. Epilepsy Res. 2009;86(1):66–71.

    Article  CAS  PubMed  Google Scholar 

  26. Vendrame M et al. Treatment of malignant migrating partial epilepsy of infancy with rufinamide: report of five cases. Epileptic Disord. 2011;13(1):18–21.

    PubMed  Google Scholar 

  27. Francois LL et al. Ketogenic regime as anti-epileptic treatment: its use in 29 epileptic children. Arch Pediatr. 2003;10(4):300–6.

    Article  PubMed  Google Scholar 

  28. Zamponi N et al. Vagus nerve stimulation (VNS) is effective in treating catastrophic 1 epilepsy in very young children. Neurosurg Rev. 2008;31(3):291–7.

    Article  PubMed  Google Scholar 

  29. Trevathan E, Murphy CC, Yeargin-Allsopp M. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 1999;40(6):748–51.

    Article  CAS  PubMed  Google Scholar 

  30. Kato M et al. Polyalanine expansion of ARX associated with cryptogenic West syndrome. Neurology. 2003;61(2):267–76.

    Article  CAS  PubMed  Google Scholar 

  31. Nemos C et al. Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature. Clin Genet. 2009;76(4):357–71.

    Article  CAS  PubMed  Google Scholar 

  32. Epi KC et al. De novo mutations in epileptic encephalopathies. Nature. 2013;501(7466):217–21.

    Article  Google Scholar 

  33. Marshall CR et al. Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11. Am J Hum Genet. 2008;83(1):106–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Otsuka M et al. STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome—result of Japanese cohort study. Epilepsia. 2010;51(12):2449–52.

    Article  CAS  PubMed  Google Scholar 

  35. Wallace RH et al. Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Neurology. 2003;61(6):765–9.

    Article  CAS  PubMed  Google Scholar 

  36. Ogiwara I et al. De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies. Neurology. 2009;73(13):1046–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dravet C. The core Dravet syndrome phenotype. Epilepsia. 2011;52 Suppl 2:3–9.

    Article  PubMed  Google Scholar 

  38. Wolff M, Casse-Perrot C, Dravet C. Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings. Epilepsia. 2006;47 Suppl 2:45–8.

    Article  PubMed  Google Scholar 

  39. Nabbout R et al. Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology. 2003;60(12):1961–7.

    Article  CAS  PubMed  Google Scholar 

  40. Harkin LA et al. Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus. Am J Hum Genet. 2002;70(2):530–6.

    Article  CAS  PubMed  Google Scholar 

  41. Patino GA et al. A functional null mutation of SCN1B in a patient with Dravet syndrome. J Neurosci. 2009;29(34):10764–78.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lossin C et al. Compromised function in the Na(v)1.2 Dravet syndrome mutation R1312T. Neurobiol Dis. 2012;47(3):378–84.

    Article  CAS  PubMed  Google Scholar 

  43. Landau WM, Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology. 1957;7(8):523–30.

    Article  CAS  PubMed  Google Scholar 

  44. Nakano S, Okuno T, Mikawa H. Landau-Kleffner syndrome. EEG topographic studies. Brain Dev. 1989;11(1):43–50.

    Article  CAS  PubMed  Google Scholar 

  45. Lesca G et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat Genet. 2013;45(9):1061–6.

    Article  CAS  PubMed  Google Scholar 

  46. Caraballo RH et al. Landau-Kleffner syndrome: a study of 29 patients. Seizure. 2014;23(2):98–104. This article provides a nice summary of the electroclinical features, etiology, treatment, and prognosis of 29 patients with Landau–Kleffner syndrome (LKS) with a long-term follow-up.

    Article  PubMed  Google Scholar 

  47. Pearl PL, Carrazana EJ, Holmes GL. The Landau-Kleffner syndrome. Epilepsy Curr. 2001;1(2):39–45.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gallagher S et al. Efficacy of very high dose steroid treatment in a case of Landau-Kleffner syndrome. Dev Med Child Neurol. 2006;48(9):766–9.

    Article  PubMed  Google Scholar 

  49. Mikati MA et al. Efficacy of intravenous immunoglobulin in Landau-Kleffner syndrome. Pediatr Neurol. 2002;26(4):298–300.

    Article  PubMed  Google Scholar 

  50. Morrell F et al. Landau-Kleffner syndrome. Treatment with subpial intracortical transection. Brain. 1995;118(Pt 6):1529–46.

    Article  PubMed  Google Scholar 

  51. Papandreou A et al. GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy. Dev Med Child Neurol. 2016;58:416–20.

    Article  PubMed  Google Scholar 

  52. VanStraten AF, Ng YT. Update on the management of Lennox-Gastaut syndrome. Pediatr Neurol. 2012;47(3):153–61.

    Article  PubMed  Google Scholar 

  53. Lemmon ME et al. Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution’s experience and summary of the literature. Dev Med Child Neurol. 2012;54(5):464–8.

    Article  PubMed  Google Scholar 

  54. Coutelier M et al. Neuroserpin mutation causes electrical status epilepticus of slow-wave sleep. Neurology. 2008;71(1):64–6.

    Article  CAS  PubMed  Google Scholar 

  55. Lesca G et al. Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism. Epilepsia. 2012;53(9):1526–38.

    Article  CAS  PubMed  Google Scholar 

  56. Zanni G et al. A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES). Epilepsy Res. 2014;108(4):811–5.

    Article  CAS  PubMed  Google Scholar 

  57. Gilfillan GD et al. SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet. 2008;82(4):1003–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rolla Shbarou MD.

Ethics declarations

Conflict of Interest

The author declares that she has no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Additional information

This article is part of the Topical Collection on Pediatric Neurology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shbarou, R. Current Treatment Options for Early-Onset Pediatric Epileptic Encephalopathies. Curr Treat Options Neurol 18, 44 (2016). https://doi.org/10.1007/s11940-016-0428-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11940-016-0428-z

Keywords

Navigation