Download PDF
Aktuelle Neurologie 2017; 44(09): 662-668
DOI: 10.1055/s-0043-110223
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Die Therapie und Prognose des refraktären und super-refraktären Status epilepticus

The Treatment and Prognosis of Refractory and Super-Refractory Status Epilepticus
Stephanie Gollwitzer
Epilepsiezentrum, Neurologische Klinik, Universitätsklinikum Erlangen
,
Hajo M. Hamer
Epilepsiezentrum, Neurologische Klinik, Universitätsklinikum Erlangen
› Author Affiliations
Further Information

Publication History

Publication Date:
06 September 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Ein Status epilepticus, der über 60 Minuten andauert und durch die Gabe von Benzodiazepinen und nicht-sedierenden Antikonvulsiva der Stufe 2 nicht beendet werden kann, wird als refraktär bezeichnet. Wenn der Status auch nach i. v.-Anästhetikagabe über 24 Stunden nicht durchbrochen werden kann, wird er als super-refraktär definiert. Zur Therapie des refraktären Status epilepticus (RSE) wird eine Kombination aus nicht-sedierenden Antikonvulsiva und i. v.-Anästhetika eingesetzt; Medikamente der ersten Wahl sind dabei Midazolam, Propofol und Thiopental. Zur Behandlung des super-refraktären Status epilepticus (SRSE) existieren keine klaren evidenz-basierten Empfehlungen, Therapieerfahrungen stützen sich überwiegend auf Einzelfallberichte und kleine Fallserien. Eingesetzt werden Ketamin, Inhalationsanästhetika, Steroide und Immunglobuline. An nicht-medikamentösen Verfahren kommen die ketogene Diät, die Elektrokonvulsionstherapie und die Epilepsiechirurgie in Betracht. Ein neues, vielversprechendes Behandlungskonzept stellt das Neurosteroid Allopregnanolon dar. Die Mortalität des RSE und SRSE hängt von der Ätiologie des Status ab und ist insgesamt deutlich höher als die des nicht-refraktären Status. In publizierten Fallserien lag sie bei ca. 30 % bzw. 50 %.

Abstract

Refractory status epilepticus (RSE) is defined as status epilepticus (SE) persisting over 60 minutes and resistant to treatment with benzodiazepines and non-sedating antiepileptic drugs. The term super-refractory status epilepticus (SRSE) refers to a refractory episode continuing under general anesthesia for more than 24 hours. RSE is treated with a combination of non-sedating AED and i. v. anesthetics; first-choice drugs are midazolam, propofol and thiopental. The management of super-refractory status epilepticus (SRSE) is challenging as clear evidence-based guidelines are lacking. Recommendations are mainly based on case reports and small case series. Therapeutic options include ketamine, inhalational anesthetics, steroids and immunoglobulins. Ketogenic diet, electroconvulsive therapy and epilepsy surgery are also considered as potentially effective. A promising new approach is the neurosteroid allopregnanolone. Mortality of RSE and SRSE is largely influenced by the etiology and is markedly higher as compared to non-refractory status epilepticus. It was reported to be about 30 % and 50 %, respectively.

Schlüsselwörter

Status epilepticus - refraktärer Status epilepticus - super-refraktärer Status epilepticus

Key words

status epilepticus - refractory status epilepticus - super-refractory status epilepticus
 

  • Literatur

  • 1 Knake S, Rosenow F, Vescovi M. et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 2001; 42: 714-718
    CrossrefPubMedGoogle Scholar
  • 2 Delaj L, Novy J, Ryvlin P. et al. Refractory and super-refractory status epilepticus in adults: a 9-year cohort study. Acta Neurol Scand 2017; 135: 92-99
    CrossrefPubMedGoogle Scholar
  • 3 Trinka E, Cock H, Hesdorffer D. et al. A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015; 56: 1515-1523
    CrossrefPubMedGoogle Scholar
  • 4 Dobesberger J, Ristic AJ, Walser G. et al. Duration of focal complex, secondarily generalized tonic-clonic, and primarily generalized tonic-clonic seizures--A video-EEG analysis. Epilepsy Behav 2015; 49: 111-117
    CrossrefPubMedGoogle Scholar
  • 5 Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011; 134: 2802-2818
    CrossrefPubMedGoogle Scholar
  • 6 Mayer SA, Claassen J, Lokin J. et al. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002; 59: 205-210
    CrossrefPubMedGoogle Scholar
  • 7 Holtkamp M, Othman J, Buchheim K. et al. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry 2005; 76: 534-539
    CrossrefPubMedGoogle Scholar
  • 8 Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005; 62: 1698-1702
    CrossrefPubMedGoogle Scholar
  • 9 Novy J, Logroscino G, Rossetti AO. Refractory status epilepticus: a prospective observational study. Epilepsia 2010; 51: 251-256
    CrossrefPubMedGoogle Scholar
  • 10 Wilder-Smith EP, Lim EC, Teoh HL. et al. The NORSE (new-onset refractory status epilepticus) syndrome: defining a disease entity. Ann Acad Med Singapore 2005; 34: 417-420
    PubMedGoogle Scholar
  • 11 Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain 2012; 135: 2314-2328
    CrossrefPubMedGoogle Scholar
  • 12 Loscher W, Brandt C. Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacol Rev 2010; 62: 668-700
    CrossrefPubMedGoogle Scholar
  • 13 Claassen J, Hirsch LJ, Emerson RG. et al. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002; 43: 146-153
    CrossrefPubMedGoogle Scholar
  • 14 Rossetti AO, Milligan TA, Vulliemoz S. et al. A randomized trial for the treatment of refractory status epilepticus. Neurocrit Care 2011; 14: 4-10
    CrossrefPubMedGoogle Scholar
  • 15 Prabhakar H, Bindra A, Singh GP. et al. Propofol versus thiopental sodium for the treatment of refractory status epilepticus. Cochrane Database Syst Rev 2012; DOI: 10.1002/14651858.CD009202.pub2. CD009202
    CrossrefPubMedGoogle Scholar
  • 16 Reznik ME, Berger K, Claassen J. Comparison of intravenous anesthetic agents for the treatment of refractory status epilepticus. J Clin Med 2016; 5: 54
    CrossrefPubMedGoogle Scholar
  • 17 Pugin D, Foreman B, De Marchis GM. et al. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study. Crit Care 2014; 18: R103
    CrossrefPubMedGoogle Scholar
  • 18 Bellante F, Legros B, Depondt C. et al. Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety. J Neurol 2016; 263: 799-806
    CrossrefPubMedGoogle Scholar
  • 19 Walli A, Poulsen TD, Dam M. et al. Propofol infusion syndrome in refractory status epilepticus: a case report and topical review. Case Rep Emerg Med 2016; 2016: 3265929
    PubMedGoogle Scholar
  • 20 Power KN, Flaatten H, Gilhus NE. et al. Propofol treatment in adult refractory status epilepticus. Mortality risk and outcome. Epilepsy Res 2011; 94: 53-60
    CrossrefPubMedGoogle Scholar
  • 21 Morrison G, Gibbons E, Whitehouse WP. High-dose midazolam therapy for refractory status epilepticus in children. Intensive Care Med 2006; 32: 2070-2076
    CrossrefPubMedGoogle Scholar
  • 22 Young GB. Status epilepticus and brain damage: pathology and pathophysiology. Adv Neurol 2006; 97: 217-220
    PubMedGoogle Scholar
  • 23 Rossetti AO, Hurwitz S, Logroscino G. et al. Prognosis of status epilepticus: role of aetiology, age, and consciousness impairment at presentation. J Neurol Neurosurg Psychiatry 2006; 77: 611-615
    CrossrefPubMedGoogle Scholar
  • 24 Marchi NA, Novy J, Faouzi M. et al. Status epilepticus: impact of therapeutic coma on outcome. Crit Care Med 2015; 43: 1003-1009
    CrossrefPubMedGoogle Scholar
  • 25 Sutter R, Marsch S, Fuhr P. et al. Anesthetic drugs in status epilepticus: risk or rescue? A 6-year cohort study. Neurology 2014; 82: 656-664
    CrossrefPubMedGoogle Scholar
  • 26 Sutter R, De Marchis GM, Semmlack S. et al. Anesthetics and outcome in status epilepticus: a matched two-center cohort study. CNS Drugs 2017; 31: 65-74
    CrossrefPubMedGoogle Scholar
  • 27 Towne AR, Waterhouse EJ, Boggs JG. et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000; 54: 340-345
    CrossrefPubMedGoogle Scholar
  • 28 Claassen J, Mayer SA, Kowalski RG. et al. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004; 62: 1743-1748
    CrossrefPubMedGoogle Scholar
  • 29 Spatola M, Novy J, Du Pasquier R. et al. Status epilepticus of inflammatory etiology: a cohort study. Neurology 2015; 85: 464-470
    CrossrefPubMedGoogle Scholar
  • 30 Gaspard N, Foreman BP, Alvarez V. et al. New-onset refractory status epilepticus: Etiology, clinical features, and outcome. Neurology 2015; 85: 1604-1613
    CrossrefPubMedGoogle Scholar
  • 31 Tan RY, Neligan A, Shorvon SD. The uncommon causes of status epilepticus: a systematic review. Epilepsy Res 2010; 91: 111-122
    CrossrefPubMedGoogle Scholar
  • 32 Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology 1993; 43: 483-488
    CrossrefPubMedGoogle Scholar
  • 33 Borris DJ, Bertram EH, Kapur J. Ketamine controls prolonged status epilepticus. Epilepsy Res 2000; 42: 117-122
    CrossrefPubMedGoogle Scholar
  • 34 Gaspard N, Foreman B, Judd LM. et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia 2013; 54: 1498-1503
    CrossrefPubMedGoogle Scholar
  • 35 Mirsattari SM, Sharpe MD, Young GB. Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol 2004; 61: 1254-1259
    CrossrefPubMedGoogle Scholar
  • 36 Vezzani A, Ruegg S. The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized: introduction. Epilepsia 2011; 52 (Suppl. 03) 1-4
    PubMedGoogle Scholar
  • 37 Zeiler FA, Matuszczak M, Teitelbaum J. et al. Plasmapheresis for refractory status epilepticus, part I: a scoping systematic review of the adult literature. Seizure 2016; 43: 14-22
    CrossrefPubMedGoogle Scholar
  • 38 Francois LL, Manel V, Rousselle C. et al. [Ketogenic regime as anti-epileptic treatment: its use in 29 epileptic children]. Arch Pediatr 2003; 10: 300-306
    CrossrefPubMedGoogle Scholar
  • 39 Thakur KT, Probasco JC, Hocker SE. et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology 2014; 82: 665-670
    CrossrefPubMedGoogle Scholar
  • 40 Strzelczyk A, Reif PS, Bauer S. et al. Intravenous initiation and maintenance of ketogenic diet: proof of concept in super-refractory status epilepticus. Seizure 2013; 22: 581-583
    CrossrefPubMedGoogle Scholar
  • 41 Legriel S, Lemiale V, Schenck M. et al. Hypothermia for Neuroprotection in Convulsive Status Epilepticus. N Engl J Med 2016; 375: 2457-2467
    CrossrefPubMedGoogle Scholar
  • 42 Niquet J, Gezalian M, Baldwin R. et al. Neuroprotective effects of deep hypothermia in refractory status epilepticus. Ann Clin Transl Neurol 2015; 2: 1105-1115
    CrossrefPubMedGoogle Scholar
  • 43 Niquet J, Baldwin R, Gezalian M. et al. Deep hypothermia for the treatment of refractory status epilepticus. Epilepsy Behav 2015; 49: 313-317
    CrossrefPubMedGoogle Scholar
  • 44 Lhatoo SD, Alexopoulos AV. The surgical treatment of status epilepticus. Epilepsia 2007; 48 (Suppl. 08) 61-65
    CrossrefPubMedGoogle Scholar
  • 45 Lisanby SH, Bazil CW, Resor SR. et al. ECT in the treatment of status epilepticus. J ECT 2001; 17: 210-215
    CrossrefPubMedGoogle Scholar
  • 46 Griesemer DA, Kellner CH, Beale MD. et al. Electroconvulsive therapy for treatment of intractable seizures. Initial findings in two children. Neurology 1997; 49: 1389-1392
    CrossrefPubMedGoogle Scholar
  • 47 Broomall E, Natale JE, Grimason M. et al. Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol 2014; 76: 911-915
    CrossrefPubMedGoogle Scholar
  • 48 Kokate TG, Cohen AL, Karp E. et al. Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice. Neuropharmacology 1996; 35: 1049-1056
    CrossrefPubMedGoogle Scholar
  • 49 Reddy K, Reife R, Cole AJ. SGE-102: a novel therapy for refractory status epilepticus. Epilepsia 2013; 54 (Suppl. 06) 81-83
    PubMedGoogle Scholar
  • 50 Towne AR, Pellock JM, Ko D. et al. Determinants of mortality in status epilepticus. Epilepsia 1994; 35: 27-34
    CrossrefPubMedGoogle Scholar
  • 51 Neligan A, Shorvon SD. Prognostic factors, morbidity and mortality in tonic-clonic status epilepticus: a review. Epilepsy Res 2011; 93: 1-10
    CrossrefPubMedGoogle Scholar
  • 52 Rossetti AO, Logroscino G, Bromfield EB. A clinical score for prognosis of status epilepticus in adults. Neurology 2006; 66: 1736-1738
    CrossrefPubMedGoogle Scholar
  • 53 Leitinger M, Holler Y, Kalss G. et al. Epidemiology-based mortality score in status epilepticus (EMSE). Neurocrit Care 2015; 22: 273-282
    CrossrefPubMedGoogle Scholar
  • 54 Foreman B, Claassen J, Abou Khaled K. et al. Generalized periodic discharges in the critically ill: a case-control study of 200 patients. Neurology 2012; 79: 1951-1960
    CrossrefPubMedGoogle Scholar
  • 55 Rossetti AO, Oddo M. The neuro-ICU patient and electroencephalography paroxysms: if and when to treat. Curr Opin Crit Care 2010; 16: 105-109
    CrossrefPubMedGoogle Scholar
  • 56 Logroscino G, Hesdorffer DC, Cascino G. et al. Short-term mortality after a first episode of status epilepticus. Epilepsia 1997; 38: 1344-1349
    CrossrefPubMedGoogle Scholar
  • 57 Kilbride RD, Reynolds AS, Szaflarski JP. et al. Clinical outcomes following prolonged refractory status epilepticus (PRSE). Neurocrit Care 2013; 18: 374-385
    CrossrefPubMedGoogle Scholar
  • 58 Cooper AD, Britton JW, Rabinstein AA. Functional and cognitive outcome in prolonged refractory status epilepticus. Arch Neurol 2009; 66: 1505-1509
    PubMedGoogle Scholar
  • 59 Bausell R, Svoronos A, Lennihan L. et al. Recovery after severe refractory status epilepticus and 4 months of coma. Neurology 2011; 77: 1494-1495
    CrossrefPubMedGoogle Scholar