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Therapie des akuten konvulsiven Anfalls und Status epilepticus im Kindesalter

  • Susanne Schubert-Bast
  • Adam Strzelczyk
Leitthema
  • 5 Downloads

Zusammenfassung

Der Status epilepticus ist der häufigste neuropädiatrische Notfall. Seit der Zulassung eines Fertigpräparates von bukkalem Midazolam hat sich dieses in der Erst- und Laientherapie etabliert. Benzodiazepine in anderer Verabreichungsform wie Midazolam nasal oder Diazepam rektal zeigen keinen Unterschied hinsichtlich der Wirksamkeit und können alternativ eingesetzt werden. Für die Therapie des Status epilepticus im Kindesalter ist derzeit keine aktuelle deutsche Leitlinie verfügbar. Nach Versagen von Benzodiazepinen ist der intravenöse Einsatz von Antikonvulsiva der nächste Schritt. Neben den etablierten Substanzen wie Phenobarbital und Phenytoin erweisen sich dabei auch neuere Antikonvulsiva wie Levetiracetam und Lacosamid als wirksam. Dabei gibt es unter den neueren Antikonvulsiva deutlich weniger Interaktionen, es besteht nicht die Gefahr der Atemsuppression und Intoxikation. Im refraktären und superrefraktären Status epilepticus kommen neben Anästhetika auch die ketogene Diät, immunmodulatorische Therapien oder eine akute Epilepsiechirurgie zum Einsatz.

Schlüsselwörter

Anfallsunterbrechung Status epilepticus Kinder Empfehlungen Statustherapie 

Treatment of acute convulsive seizures and status epilepticus in childhood

Abstract

Status epilepticus is the most common neuropediatric emergency. Since the approval of a prefabricated compound of buccal midazolam, this has become established for initial treatment by caregivers and first-responders. Other nonintravenous benzodiazepines, such as nasal midazolam or rectal diazepam show no differences in efficacy and can be used as an alternative. At the moment there are no current German guidelines available for the treatment of status epilepticus in children. Escalation of treatment with intravenous anticonvulsants is recommended after failure of benzodiazepines. In addition to phenytoin and phenobarbital, recent studies have shown that newer anticonvulsants, such as levetiracetam and lacosamide are effective. There are far fewer interactions of the new anticonvulsants and no risks of respiratory suppression or intoxication. Anesthetics are the next therapeutic option for refractory and super-refractory status epilepticus, as well as a ketogenic diet, immunomodulatory treatment, other oral anticonvulsants and epilepsy surgery.

Keywords

Seizure interruption Status epilepticus Children Recommendation status therapy 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

S. Schubert-Bast erhielt Beratungs- und Referentenhonorare von Desitin Arzneimittel, Eisai, UCB Pharma, LivaNova und Zogenix. A. Strzelczyk erhielt Beratungs‑, Referentenhonorare und/oder Unterstützung für Forschungsvorhaben von Desitin Arzneimittel, Eisai, LivaNova, Sage Therapeutics, UCB Pharma und Zogenix.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Abend NS, Gutierrez-Colina AM, Monk HM et al (2011) Levetiracetam for treatment of neonatal seizures. J Child Neurol 26:465–470.  https://doi.org/10.1177/0883073810384263 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Abend NS, Loddenkemper T (2014) Management of pediatric status epilepticus. Curr Treat Options Neurol 16:301.  https://doi.org/10.1007/s11940-014-0301-x CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Agarwal P, Kumar N, Chandra R et al (2007) Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure 16:527–532.  https://doi.org/10.1016/j.seizure.2007.04.012 CrossRefPubMedGoogle Scholar
  4. 4.
    Akyildiz BN, Kumandaş S (2011) Treatment of pediatric refractory status epilepticus with topiramate. Childs Nerv Syst 27:1425–1430.  https://doi.org/10.1007/s00381-011-1432-y CrossRefPubMedGoogle Scholar
  5. 5.
    Alford EL, Wheless JW, Phelps SJ (2015) Treatment of generalized convulsive status epilepticus in pediatric patients. J Pediatr Pharmacol Ther 20:260–289.  https://doi.org/10.5863/1551-6776-20.4.260 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Alldredge BK, Gelb AM, Isaacs SM et al (2001) A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 345:631–637.  https://doi.org/10.1056/NEJMoa002141 CrossRefPubMedGoogle Scholar
  7. 7.
    Almaabdi KH, Alshehri RO, Althubiti AA et al (2014) Intravenous methylprednisolone for intractable childhood epilepsy. Pediatr Neurol 50:334–336.  https://doi.org/10.1016/j.pediatrneurol.2013.12.015 CrossRefPubMedGoogle Scholar
  8. 8.
    Appavu B, Vanatta L, Condie J et al (2016) Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure 41:62–65.  https://doi.org/10.1016/j.seizure.2016.07.006 CrossRefPubMedGoogle Scholar
  9. 9.
    Arkilo D, Gustafson M, Ritter FJ (2016) Clinical experience of intravenous lacosamide in infants and young children. Eur J Paediatr Neurol 20:212–217.  https://doi.org/10.1016/j.ejpn.2015.12.013 CrossRefPubMedGoogle Scholar
  10. 10.
    Ashrafi MR, Khosroshahi N, Karimi P et al (2010) Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children. Eur J Paediatr Neurol 14:434–438.  https://doi.org/10.1016/j.ejpn.2010.05.009 CrossRefPubMedGoogle Scholar
  11. 11.
    Baalen AV, Häusler M, Boor R et al (2010) Febrile infection–related epilepsy syndrome (FIRES): a nonencephalitic encephalopathy in childhood. Epilepsia 51:1323–1328.  https://doi.org/10.1111/j.1528-1167.2010.02535.x CrossRefPubMedGoogle Scholar
  12. 12.
    Brigo F, Lattanzi S, Rohracher A et al (2018) Perampanel in the treatment of status epilepticus: a systematic review of the literature. Epilepsy Behav 86:179–186.  https://doi.org/10.1016/j.yebeh.2018.07.004 CrossRefPubMedGoogle Scholar
  13. 13.
    Broomall E, Natale JE, Grimason M et al (2014) Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol 76:911–915.  https://doi.org/10.1002/ana.24295 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Brophy GM, Bell R, Claassen J et al (2012) Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 17:3–23.  https://doi.org/10.1007/s12028-012-9695-z CrossRefPubMedGoogle Scholar
  15. 15.
    Chen L, Feng P, Wang J et al (2009) Intravenous sodium valproate in mainland China for the treatment of diazepam refractory convulsive status epilepticus. J Clin Neurosci 16:524–526.  https://doi.org/10.1016/j.jocn.2008.06.007 CrossRefPubMedGoogle Scholar
  16. 16.
    Chin RF, Neville BG, Peckham C et al (2006) Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet 368:222–229.  https://doi.org/10.1016/S0140-6736(06)69043-0 CrossRefPubMedGoogle Scholar
  17. 17.
    Fişgin T, Gurer Y, Tezic T et al (2002) Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol 17:123–126.  https://doi.org/10.1177/088307380201700206 CrossRefPubMedGoogle Scholar
  18. 18.
    Gaínza-Lein M, Fernández IS, Jackson M et al (2018) Association of time to treatment with short-term outcomes for pediatric patients with refractory convulsive status epilepticus. JAMA Neurol 75:410–418.  https://doi.org/10.1001/jamaneurol.2017.4382 CrossRefPubMedGoogle Scholar
  19. 19.
    Glauser T, Shinnar S, Gloss D et al (2016) Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the guideline committee of the American Epilepsy Society. Epilepsy Curr 16:48–61.  https://doi.org/10.5698/1535-7597-16.1.48 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hattori H, Yamano T, Hayashi K et al (2008) Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan. Brain Dev 30:504–512.  https://doi.org/10.1016/j.braindev.2007.12.016 CrossRefPubMedGoogle Scholar
  21. 21.
    Höfler J, Rohracher A, Kalss G et al (2016) (S)-ketamine in refractory and super-refractory status epilepticus: a retrospective study. CNS Drugs 30:869–876.  https://doi.org/10.1007/s40263-016-0371-2 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kadel J, Bauer S, Hermsen AM et al (2018) Use of emergency medication in adult patients with epilepsy: a multicentre cohort study from Germany. CNS Drugs 32:771–781.  https://doi.org/10.1007/s40263-018-0544-2 CrossRefPubMedGoogle Scholar
  23. 23.
    Kay L, Reif PS, Belke M et al (2015) Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures. Epilepsia 56:1408–1414.  https://doi.org/10.1111/epi.13088 CrossRefPubMedGoogle Scholar
  24. 24.
    Kramer U, Chi C‑S, Lin K‑L et al (2011) Febrile infection–related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome. Epilepsia 52:1956–1965.  https://doi.org/10.1111/j.1528-1167.2011.03250.x CrossRefPubMedGoogle Scholar
  25. 25.
    Lang N, Lange M, Schmitt FC et al (2016) Intravenous lacosamide in clinical practice-results from an independent registry. Seizure 39:5–9.  https://doi.org/10.1016/j.seizure.2016.01.008 CrossRefPubMedGoogle Scholar
  26. 26.
    Lowenstein DH, Bleck T, Macdonald RL (1999) It’s time to revise the definition of status epilepticus. Epilepsia 40:120–122.  https://doi.org/10.1111/j.1528-1157.1999.tb02000.x CrossRefPubMedGoogle Scholar
  27. 27.
    Malamiri RA, Ghaempanah M, Khosroshahi N et al (2012) Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Eur J Paediatr Neurol 16:536–541.  https://doi.org/10.1016/j.ejpn.2012.01.012 CrossRefPubMedGoogle Scholar
  28. 28.
    McIntyre J, Robertson S, Norris E et al (2005) Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 366:205–210.  https://doi.org/10.1016/S0140-6736(05)66909-7 CrossRefPubMedGoogle Scholar
  29. 29.
    McTague A, Kneen R, Kumar R et al (2012) Intravenous levetiracetam in acute repetitive seizures and status epilepticus in children: experience from a children’s hospital. Seizure 21:529–534.  https://doi.org/10.1016/j.seizure.2012.05.010 CrossRefPubMedGoogle Scholar
  30. 30.
    McTague A, Martland T, Appleton R (2018) Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD001905.pub3 CrossRefPubMedGoogle Scholar
  31. 31.
    Misra UK, Kalita J, Maurya PK (2012) Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study. J Neurol 259:645–648.  https://doi.org/10.1007/s00415-011-6227-2 CrossRefPubMedGoogle Scholar
  32. 32.
    Möddel G, Kellinghaus C, Strzelczyk A (2018) Initiale Therapie des Status epilepticus: Welche Therapie erfolgt zu Hause und im Rettungswagen? Z Epileptol.  https://doi.org/10.1007/s10309-018-0204-z CrossRefGoogle Scholar
  33. 33.
    Navarro V, Dagron C, Elie C et al (2016) Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial. Lancet 15:47–55.  https://doi.org/10.1016/S1474-4422(15)00296-3 CrossRefPubMedGoogle Scholar
  34. 34.
    Nicolas J‑M, Hannestad J, Holden D et al (2016) Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 57:201–209.  https://doi.org/10.1111/epi.13267 CrossRefPubMedGoogle Scholar
  35. 35.
    Niquet J, Suchomelova L, Thompson K et al (2017) Acute and long-term effects of brivaracetam and brivaracetam-diazepam combinations in an experimental model of status epilepticus. Epilepsia 58:1199–1207.  https://doi.org/10.1111/epi.13787 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Poddar K, Sharma R, Ng Y‑T (2016) Intravenous lacosamide in pediatric status epilepticus: an open-label efficacy and safety study. Pediatr Neurol 61:83–86.  https://doi.org/10.1016/j.pediatrneurol.2016.03.021 CrossRefPubMedGoogle Scholar
  37. 37.
    Prabhakar H, Kalaivani M (2017) Propofol versus thiopental sodium for the treatment of refractory status epilepticus. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.cd009202.pub4 CrossRefPubMedGoogle Scholar
  38. 38.
    Riss J, Cloyd J, Gates J, Collins S (2008) Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand 118:69–86.  https://doi.org/10.1111/j.1600-0404.2008.01004.x CrossRefPubMedGoogle Scholar
  39. 39.
    Rosati A, Ilvento L, L’Erario M et al (2016) Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01). BMJ Open 6:e11565.  https://doi.org/10.1136/bmjopen-2016-011565 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Rosenow F (2012) Status epilepticus im Erwachsenenalter. In: Diener HC, Weimar C (Hrsg) Leitlinien für Diagnostik und Therapie in der NeurologieGoogle Scholar
  41. 41.
    Rosenthal ES, Claassen J, Wainwright MS et al (2017) Brexanolone as adjunctive therapy in super‐refractory status epilepticus. Ann Neurol 82:342–352.  https://doi.org/10.1002/ana.25008 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Sánchez Fernández I, Goodkin HP, Scott RC (2018) Pathophysiology of convulsive status epilepticus. Seizure.  https://doi.org/10.1016/j.seizure.2018.08.002 CrossRefPubMedGoogle Scholar
  43. 43.
    Shaner DM, McCurdy SA, Herring MO, Gabor AJ (1988) Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Baillieres Clin Neurol 38:202–207Google Scholar
  44. 44.
    Shinnar S, Pellock JM, Moshé SL et al (1997) In whom does status epilepticus occur: age‐related differences in children. Epilepsia 38:907–914.  https://doi.org/10.1111/j.1528-1157.1997.tb01256.x CrossRefPubMedGoogle Scholar
  45. 45.
    Shorvon S, Ferlisi M (2011) The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 134:2802–2818.  https://doi.org/10.1093/brain/awr215 CrossRefPubMedGoogle Scholar
  46. 46.
    Silbergleit R, Lowenstein D, Durkalski V, Conwit R (2011) RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of IM midazolam versus IV lorazepam in the pre-hospital treatment of status epilepticus by paramedics. Epilepsia 52:45–47.  https://doi.org/10.1111/j.1528-1167.2011.03235.x CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Standish JC, Hilmas E, Falchek SJ (2011) Levetiracetam for the treatment of pediatric status epilepticus: a case series. J Pediatr Neurol 9:195–201.  https://doi.org/10.3233/JPN-2011-0458 CrossRefGoogle Scholar
  48. 48.
    Strzelczyk A, Ansorge S, Hapfelmeier J et al (2017) Costs, length of stay, and mortality of super-refractory status epilepticus: a population-based study from Germany. Epilepsia 58:1533–1541.  https://doi.org/10.1111/epi.13837 CrossRefPubMedGoogle Scholar
  49. 49.
    Strzelczyk A, Kay L, Bauer S et al (2018) Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus. Epilepsia 59:1549–1556.  https://doi.org/10.1111/epi.14476 CrossRefPubMedGoogle Scholar
  50. 50.
    Strzelczyk A, Kortland L‑M, Knake S, Rosenow F (2015) Stiripentol for the treatment of super-refractory status epilepticus. Acta Neurol Scand 132:435–439.  https://doi.org/10.1111/ane.12403 CrossRefPubMedGoogle Scholar
  51. 51.
    Strzelczyk A, Reif PS, Bauer S et al (2013) Intravenous initiation and maintenance of ketogenic diet: proof of concept in super-refractory status epilepticus. Seizure 22:581–583.  https://doi.org/10.1016/j.seizure.2013.03.007 CrossRefPubMedGoogle Scholar
  52. 52.
    Strzelczyk A, Steinig I, Willems LM et al (2017) Treatment of refractory and super-refractory status epilepticus with brivaracetam: a cohort study from two German university hospitals. Epilepsy Behav 70:177–181.  https://doi.org/10.1016/j.yebeh.2017.03.028 CrossRefPubMedGoogle Scholar
  53. 53.
    Strzelczyk A, Zöllner JP, Willems LM et al (2017) Lacosamide in status epilepticus: systematic review of current evidence. Epilepsia 58:933–950.  https://doi.org/10.1111/epi.13716 CrossRefPubMedGoogle Scholar
  54. 54.
    Sutter R, Marsch S, Fuhr P et al (2014) Anesthetic drugs in status epilepticus: risk or rescue? Baillieres Clin Neurol 82:656–664.  https://doi.org/10.1212/WNL.0000000000000009 CrossRefGoogle Scholar
  55. 55.
    Trinka E, Cock H, Hesdorffer D et al (2015) A definition and classification of status epilepticus—report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 56:1515–1523.  https://doi.org/10.1111/epi.13121 CrossRefGoogle Scholar
  56. 56.
    Uberall MA, Trollmann R, Wunsiedler U, Wenzel D (2000) Intravenous valproate in pediatric epilepsy patients with refractory status epilepticus. Baillieres Clin Neurol 54:2188–2189Google Scholar
  57. 57.
    Vasquez A, Farias-Moeller R, Tatum W (2018) Pediatric refractory and super-refractory status epilepticus. Seizure.  https://doi.org/10.1016/j.seizure.2018.05.012 CrossRefPubMedGoogle Scholar
  58. 58.
    Vasquez A, Gaínza-Lein M, Fernández IS et al (2018) Hospital emergency treatment of convulsive status epilepticus: comparison of pathways from ten pediatric research centers. Pediatr Neurol.  https://doi.org/10.1016/j.pediatrneurol.2018.06.004 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Zentrum für Kinder- und Jugendmedizin, NeuropädiatrieGoethe-Universität FrankfurtFrankfurt am MainDeutschland
  2. 2.Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und NeurochirurgieGoethe-Universität FrankfurtFrankfurt am MainDeutschland

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