Subscribe to RSS
DOI: 10.1055/s-0032-1314862
Klinik und Therapie des konvulsiven Status epilepticus
The Clinical Forms and the Treatment of Status EpilepticusPublication History
Publication Date:
22 June 2012 (online)
![](https://www.thieme-connect.de/media/klinneuro/201202/lookinside/thumbnails/10.1055-s-0032-1314862-1.jpg)
Zusammenfassung
Status epilepticus (SE) als die schwerste und extremste Ausprägung eines epileptischen Anfalls weist eine Sterblichkeit von ca. 20% auf. Der generalisiert tonisch klonische SE (GTKSE) wird nach dem zeitlichen Auftreten in 4 Stufen eingeteilt: (Stufe1) Frühphase, (Stufe 2) etablierter SE, (Stufe 3) fortgeschrittener SE, (Stufe 4) superrefraktärer SE. Die Therapiestrategie ist abhängig von der jeweiligen Stufe. Therapie der Wahl sind bei Stufe 1 die Benzodiazepine. Bei Versagen folgt in Stufe 2 die rasche Gabe von Antiepileptika (Phenytoin/Fosphenytoin, Phenobarbital, Valproat, Levetiracetam). Bei Nichtsistieren des SE folgen in Stufe 3 Anästhetika (Thiopental, Midazolam, Propofol). Zur Therapie in Stufe 4 existieren lediglich Fallserien. Dieser Review spiegelt die aktuellen klinischen Erfahrungen und Evidenz der Therapiestrategie bei GTKSE wieder.
Abstract
Status epilepticus (SE) is one of the most common and severe neurological emergencies, associated with a mortality up to 20%. Depending on time course, tonic clonic status epilepticus (CSE) is divided into: (phase 1) premonitory SE; (phase 2) established SE; (phase 3) subtle SE and (phase 4) super-refractory SE. Standard treatment options for phase 1 are benzodiazepines, after failure in phase 2 intravenous phenytoin/fosphenytoin, phenobarbital, valproic acid or levetiracetam; thiopental, midazolam and propofol are recommended in phase 3 and for the treatment of phase 4 only case reports exist. This review summarises the current clinical experience and evidence concerning the treatment for CSE.
-
Literatur
- 1 Wilson JV, Reynolds EH. Texts and documents. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. Med Hist 1990; 34: 185-198
- 2 Temkin O. The falling sickness: a history of epilepsy from the Greeks to the beginnings. London and Baltimore: Johns Hopkins Press; 1971
- 3 Wolf P, Trinka E, Bauer G. Absence status epilepticus: The first documented case?. Epilepsia 2007; 48: 4-5
- 4 Clark LP, Prout TP. Status epilepticus: a clinical and pathological study in epilepsy [part1]. American Journal of Insanity 1903; 60: 291-306
- 5 Clark LP, Prout TP. Status epilepticus: a clinical and pathological study in epilepsy [part 2]. American Journal of Insanity 1903; 60: 645-675
- 6 Clark LP, Prout TP. Status epilepticus: a clinical and pathological study in epilepsy [part 3]. American Journal of Insanity 1904; 61: 81-108
- 7 Shorvon S, Trinka E. Status epilepticus – making progress. Epilepsia 2011; 52 (Suppl. 08) 1-2
- 8 Shorvon S. Super-refractory status epilepticus: an approach to therapy in this difficult clinical situation. Epilepsia 2011; 52 (Suppl. 08) 53-56
- 9 Kalita J, Misra UK, Patel R. Initial EEG in status epilepticus is helpful in predicting seizure recurrence. Electromyogr Clin Neurophysiol 2006; 46: 139-144
- 10 Pandian JD, Cascino GD, So EL et al. Digital video-electroencephalographic monitoring in the neurological-neurosurgical intensive care unit: clinical features and outcome. Arch Neurol 2004; 61: 1090-1094
- 11 Claassen J, Hirsch LJ, Emerson RG et al. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 2001; 57: 1036-1042
- 12 Hirsch LJ. Continuous EEG monitoring in the intensive care unit: an overview. J Clin Neurophysiol 2004; 21: 332-340
- 13 Hirsch LJ. Brain monitoring: the next frontier of ICU monitoring. J Clin Neurophysiol 2004; 21: 305-306
- 14 Hirsch LJ, Kull LL. Continuous EEG monitoring in the intensive care unit. Am J Electroneurodiagnostic Technol 2004; 44: 137-158
- 15 Jette N, Hirsch LJ. Continuous electroencephalogram monitoring in critically ill patients. Curr Neurol Neurosci Rep 2005; 5: 312-21
- 16 Wittman Jr JJ, Hirsch LJ. Continuous electroencephalogram monitoring in the critically ill. Neurocrit Care 2005; 2: 330-341
- 17 Jaitly R, Sgro JA, Towne AR et al. Prognostic value of EEG monitoring after status epilepticus: a prospective adult study. J Clin Neurophysiol 1997; 14: 326-334
- 18 Feddersen B, Trinka E. Status epilepticus. Nervenarzt 2012;
- 19 Amzica F, Kroeger D. Cellular mechanisms underlying EEG waveforms during coma. Epilepsia 2011; 52 (Suppl. 08) 25-27
- 20 Amzica F. Basic physiology of burst-suppression. Epilepsia 2009; 50 (Suppl. 12) 38-39
- 21 Krishnamurthy KB, Drislane FW. Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus. Epilepsia 1999; 40: 759-762
- 22 Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005; 62: 1698-1702
- 23 Shorvon S, Trinka E, Walker M. First London Colloquium on Status Epilepticus. Epilepsia 2007; 48: 1-3
- 24 Trinka E, Shorvon S. The proceedings of the Innsbruck Colloquium on Status Epilepticus. Epilepsia 2009; 50 (Suppl. 12) 1-2
- 25 Cock HR. Established status epilepticus treatment trial (ESETT). Epilepsia 2011; 52 (Suppl. 08) 50-52
- 26 Shorvon S, Baulac M, Cross H et al. The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on Status Epilepticus. Epilepsia 2008; 49: 1277-1285
- 27 Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology. 1993 43. 483-488
- 28 Trinka E. Benzodiazepines used primarily for emergency treatment (Diazepam, Lorazepam, and Midazolam). In: Shorvon SD, Perucca E, Engel Jr J. (eds.) Treatment of Epilepsies. Oxford: Blackwell Publishing; 2009: 470-484
- 29 Treiman DM, Meyers PD, Walton NY et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 1998; 339: 792-798
- 30 Leppik IE, Derivan AT, Homan RW et al. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983; 249: 1452-1454
- 31 Alldredge BK, Gelb AM, Isaacs SM et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001; 345: 631-637
- 32 Prasad K, Krishnan PR, Al Roomi K et al. Anticonvulsant therapy for status epilepticus. Br J Clin Pharmacol 2007; 63: 640-647
- 33 Meierkord H, Boon P, Engelsen B et al. EFNS guideline on the management of status epilepticus. Eur J Neurol 2006; 13: 445-450
- 34 Dreifuss FE, Rosman NP, Cloyd JC et al. A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med 1998; 338: 1869-1875
- 35 Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet 1999; 353: 623-626
- 36 McIntyre J, Robertson S, Norris E et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 2005; 366: 205-210
- 37 Mpimbaza A, Ndeezi G, Staedke S et al. Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial. Pediatrics 2008; 121: e58-e64
- 38 Baysun S, Aydin OF, Atmaca E et al. A comparison of buccal midazolam and rectal diazepam for the acute treatment of seizures. Clin Pediatr (Phila) 2005; 44: 771-776
- 39 Lahat E, Goldman M, Barr J et al. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ 2000; 321: 83-86
- 40 Fisgin T, Gurer Y, Tezic T et al. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol 2002; 17: 123-126
- 41 Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol 2006; 34: 355-359
- 42 Silbergleit R, Durkalski V, Lowenstein D et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 2012; 366: 591-600
- 43 Silbergleit R, Lowenstein D, Durkalski V et al. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia 2011; 52 (Suppl. 08) 45-47
- 44 Trinka E, Dobesberger J. New Treatment Options in Status Epilepticus: a critical review on levetiracetam. Therap Adv Neurol Dis 2009; 2: 79-91
- 45 Trinka E. What is the evidence to use new intravenous AEDs in status epilepticus?. Epilepsia 2011; 52 (Suppl. 08) 35-38
- 46 Wilder BJ, Ramsay RE, Willmore LJ et al. Efficacy of intravenous phenytoin in the treatment of status epilepticus: kinetics of central nervous system penetration. Ann Neurol 1977; 1: 511-518
- 47 Cranford RE, Leppik IE, Patrick B et al. Intravenous phenytoin in acute treatment of seizures. Neurology 1979; 29: 1474-1479
- 48 Leppik IE, Patrick BK, Cranford RE. Treatment of acute seizures and status epilepticus with intravenous phenytoin. Adv Neurol 1983; 34: 447-451
- 49 Burneo JG, Anandan JV, Barkley GL. A prospective study of the incidence of the purple glove syndrome. Epilepsia 2001; 42: 1156-1159
- 50 O’Brien TJ, Cascino GD, So EL et al. Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin. Neurology 1998; 51: 1034-1039
- 51 Knapp LE, Kugler AR. Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy. J Child Neurol 1998; 13 (Suppl. 01) S15-S18
- 52 Wilder BJ, Campbell K, Ramsay RE et al. Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery. Arch Neurol 1996; 53: 764-768
- 53 Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998; 338: 970-976
- 54 Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 2002; 16: 695-714
- 55 Zaccara G, Franciotta D, Perucca E. Idiosyncratic Adverse Reactions to Antiepileptic Drugs. Epilepsia 2007;
- 56 Genton P, Semah F, Trinka E. Valproic acid in epilepsy: pregnancy-related issues. Drug Saf 2006; 29: 1-21
- 57 Gerstner T, Busing D, Bell N et al. Valproic acid-induced pancreatitis: 16 new cases and a review of the literature. J Gastroenterol 2007; 42: 39-48
- 58 Konig SA, Schenk M, Sick C et al. Fatal liver failure associated with valproate therapy in a patient with Friedreich’s disease: review of valproate hepatotoxicity in adults. Epilepsia 1999; 40: 1036-1040
- 59 Konig SA, Siemes H, Blaker F et al. Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities. Epilepsia 1994; 35: 1005-1015
- 60 Hussein Z, Mukherjee D, Lamm J et al. Pharmacokinetics of valproate after multiple-dose oral and intravenous infusion administration: gastrointestinal-related diurnal variation. J Clin Pharmacol 1994; 34: 754-759
- 61 Hussein Z, Patterson KJ, Lamm JE et al. Effect of infusion duration on valproate pharmacokinetics. Biopharm Drug Dispos 1993; 14: 389-399
- 62 Venkataraman V, Wheless JW. Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients. Epilepsy Res 1999; 35: 147-153
- 63 Wheless JW, Vazquez BR, Kanner AM et al. Rapid infusion with valproate sodium is well tolerated in patients with epilepsy. Neurology 2004; 63: 1507-1508
- 64 Naritoku DK, Mueed S. Intravenous loading of valproate for epilepsy. Clin Neuropharmacol 1999; 22: 102-106
- 65 Ramsay RE, Cantrell D, Collins SD et al. Safety and tolerance of rapidly infused Depacon. A randomized trial in subjects with epilepsy. Epilepsy Res 2003; 52: 189-201
- 66 Sinha S, Naritoku DK. Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology 2000; 55: 722-724
- 67 Honack D, Loscher W. Intravenous valproate: onset and duration of anticonvulsant activity against a series of electroconvulsions in comparison with diazepam and phenytoin. Epilepsy Res 1992; 13: 215-221
- 68 Walton NY, Treiman DM. Valproic acid treatment of experimental status epilepticus. Epilepsy Res 1992; 12: 199-205
- 69 Limdi NA, Shimpi AV, Faught E et al. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 2005; 64: 353-355
- 70 Limdi NA, Faught E. The safety of rapid valproic acid infusion. Epilepsia 2000; 41: 1342-1345
- 71 Kramer G, Bergmann A, Deshpande LS et al. Current Place of Intravenous Valproic Acid in the Treatment of Generalized Tonic-Clonic Status Epilepticus. Aktuelle Neurologie 2005; 32 (05) 263-274 Ref Type: Journal (Full)
- 72 Limdi NA, Knowlton RK, Cofield SS et al. Safety of rapid intravenous loading of valproate. Epilepsia 2007; 48: 478-483
- 73 Teich M, Longin E, Dempfle CE et al. Factor XIII deficiency associated with valproate treatment. Epilepsia 2004; 45: 187-189
- 74 Beenen LF, Lindeboom J, Kasteleijn-Nolst Trenite DG et al. Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects. J Neurol Neurosurg Psychiatry 1999; 67: 474-480
- 75 Ward MM, Barbaro NM, Laxer KD et al. Preoperative valproate administration does not increase blood loss during temporal lobectomy. Epilepsia 1996; 37: 98-101
- 76 Anderson GD, Lin YX, Berge C et al. Absence of bleeding complications in patients undergoing cortical surgery while receiving valproate treatment. J Neurosurg 1997; 87: 252-256
- 77 Andersen V, Sonne J, Andersen M. Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999. Eur J Clin Pharmacol 2001; 57: 517-521
- 78 Embacher N, Karner E, Wanschitz J et al. Acute encephalopathy after intravenous administration of valproate in non-convulsive status epilepticus. Eur J Neurol 2006; 13: e5-e6
- 79 Scheffner D, Konig S, Rauterberg-Ruland I et al. Fatal liver failure in 16 children with valproate therapy. Epilepsia 1988; 29: 530-542
- 80 Otoul C, Arrigo C, van Rijckevorsel K et al. Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy. Clin Neuropharmacol 2005; 28: 72-78
- 81 Gidal BE, Baltes E, Otoul C et al. Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. Epilepsy Res 2005; 64: 1-11
- 82 Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 2004; 43: 707-724
- 83 Mazarati AM, Baldwin R, Klitgaard H et al. Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combinations in experimental status epilepticus. Epilepsy Res 2004; 58: 167-174
- 84 Shaner DM, McCurdy SA, Herring MO et al. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology 1988; 38: 202-207
- 85 Ben Menachem E, Biton V, Jatuzis D et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007; 48: 1308-1317
- 86 Krauss G, Ben-Menachem E, Mameniskiene R et al. Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures. Epilepsia 2010; 51: 951-957
- 87 Biton V, Rosenfeld WE, Whitesides J et al. Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. Epilepsia 2008; 49: 418-424
- 88 Kellinghaus C, Berning S, Besselmann M. Intravenous lacosamide as successful treatment for nonconvulsive status epilepticus after failure of first-line therapy. Epilepsy Behav 2009; 14: 429-431
- 89 Mayer SA, Claassen J, Lokin J et al. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002; 59: 205-210
- 90 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
- 91 Kalviainen R, Eriksson K, Parviainen I. Refractory generalised convulsive status epilepticus: a guide to treatment. CNS Drugs 2005; 19: 759-768
- 92 Rossetti AO. Which anaesthetic should be used in the treatment of refractory status epilepticus?. Epilepsia 2007; Ref Type: In Press
- 93 Holtkamp M. The anaesthetic and intensive care of status epilepticus. Curr Opin Neurol 2007; 20: 188-193
- 94 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
- 95 Niermeijer JM, Uiterwaal CS, Van Donselaar CA. Propofol in status epilepticus: little evidence, many dangers?. J Neurol 2003; 250: 1237-1240
- 96 Vasile B, Rasulo F, Candiani A et al. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med 2003; 29: 1417-1425
- 97 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
- 98 Walker MC, Howard RS, Smith SJ et al. Diagnosis and treatment of status epilepticus on a neurological intensive care unit. QJM 1996; 89: 913-920
- 99 Holtkamp M, Othman J, Buchheim K et al. Diagnosis of psychogenic nonepileptic status epilepticus in the emergency setting. Neurology 2006; 66: 1727-1729