Notfälle im Bereich der Epilepsien

 

 Buy Article Permissions and Reprints

Zusammenfassung

Der Status epilepticus (SE) ist der nach dem Schlaganfall häufigste neurologische Notfall. Er stellt als generalisierter konvulsiver SE (GKSE) die schwerste Ausprägung eines epileptischen Anfalls dar, der mit einer signifikanten Morbidität und einer ca. 20%igen Letalität verbunden ist. Nur bei der Hälfte der Patienten mit SE besteht zuvor eine Epilepsie; die meisten Fälle sind symptomatisch, wobei SchädelHirn-Traumata, zerebrovaskuläre Erkrankungen, ZNS-Infektionen und metabolische Ursachen führend sind. Bei Patienten mit vorbestehender Epilepsie lässt sich eine frühe Phase des GKSE erkennen, in der die Anfälle crescendoartig zunehmen, bis sie in kontinuierliche Anfallsaktivität münden (etablierte Phase). Das Management eines GKSE verlangt rasches und beherztes Vorgehen. Neben der sofort einzuleitenden Therapie muss gleichzeitig die artdiagnostische Zuordnung des SE und die Ursache erkannt und behandelt werden. Als Therapie der ersten Wahl sind Benzodiazepine etabliert, wobei intravenösem (i.v.) Lorazepam gegenüber Diazepam der Vorzug zu geben ist. Versagt die Therapie mit Benzodiazepinen, muss rasch und konsequent nach einem Stufenschema vorgegangen werden. Phenytoin/Fosphenytoin, Valproinsäure und Levetiracetam sind als i.v.-Formulierung erhältliche Antiepileptika. Obwohl Vergleichsstudien fehlen wird Phenytoin bevorzugt. Valproat i.v. ist nicht sedierend und kardiovaskulär gut verträglich, sodass es hier eine attraktive Alternative zu Phenytoin darstellt. Levetiracetam ist eine viel versprechende neue Therapieoption, deren Stellenwert erst bestimmt werden muss. Versagt auch die zweite Therapiestufe, so muss der Patient intubiert und in Allgemeinanästhesie intensivmedizinisch behandelt werden. Dafür stehen Thiopental, Propofol oder hochdosiertes Midazolam zur Verfügung. Durch den eklatanten Mangel an randomisierten Studien bleibt die Therapie des GKSE empirisch und durch den Offlabel-Einsatz auch in medizinrechtlicher Hinsicht problematisch. Dieser Übersichtsartikel behandelt praxisnah die Probleme und häufig gemachte Fehler in der Diagnose und Therapie des GKSE.

Summary

Status epilepticus is – only second to stroke – the most common neurological emergency situation. Generalized convulsive status epilepticus (GCSE), the most severe and extreme expression of an epileptic seizure, is associated with a significant morbidity and one out of five patients will not survive. Only half of the patients have pre-existing epilepsy and the majority is acute or remote symptomatic, with brain trauma, cerebrovascular insults, brain infections and metabolic diseases as the most common causes. In patients with previous epilepsya phase of increasing seizure activity (premonitory status) often heralds overt GCSE in which continuous epileptic activity prevails. Management of established GCSE prompts immediate and vigorous emergency treatment. Diagnostic workup should reveal the aetiology of GCSE but must not delay treatment. Intravenous (IV) benzodiazepines are the treatment of choice in the early phases of GCSE. Randomized controlled trials have shown that IV lorazepam is superior to diazepam. When seizures or ictal electroencephalographic activity persists after IV benzodiazepines a rapid infusion with antiepileptic drugs is necessary at this stage. Though randomized controlled studies are not available, IV phenytoin is most often used. A clinically useful alternative devoid of cardiovascular and central depressant side effects is IV valproate. Recently an IV formulation of levetiracetam has been marketed, but experience to date is too limited to draw conclusions. Failure to respond to IV antiepileptic drugs should lead to general anaesthesia in the intensive care setting without any delay. High-dose continuous midazolam, propofol or thiopental are the most often used anaesthetics at this, so called refractory stage. Due to the obvious lack of randomised controlled trials the treatment of GCSE remains empiric and includes often drugs not licensed for this indication posing serious medico legal problems on the treating physician. This review highlights practical aspects in the treatment of GCSE and discusses the most important pitfalls in the management of these patients.

• Literatur

• 1 Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America’s Working Group on Status Epilepticus. JAMA 1993; 270 (07) 854-859.
  CrossrefPubMedGoogle Scholar
• 2 Aichner F. Semiologie der Grand mal Anfälle. Medizinische Universität Innsbruck 2005
  PubMedGoogle Scholar
• 3 Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S. et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001; 345 (09) 631-637.
  CrossrefPubMedGoogle Scholar
• 4 Andersen V, Sonne J, Andersen M. Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999. Eur J Clin Pharmacol 2001; 57 (6–7): 517-521.
  CrossrefPubMedGoogle Scholar
• 5 Anderson GD, Lin YX, Berge C, Ojemann GA. Absence of bleeding complications in patients undergoing cortical surgery while receiving valproate treatment. J Neurosurg 1997; 87 (02) 252-256.
  CrossrefPubMedGoogle Scholar
• 6 Bauer G, Bauer R, Pfausler B, Trinka E. Nonconvulsive Status Epilepticus and Coma. Epileptologia 2006; 14: 195-206.
  Google Scholar
• 7 Bauer G, Niedermeyer E. Acute convulsions. Clin Electroencephalogr 1979; 10 (03) 127-144.
  CrossrefPubMedGoogle Scholar
• 8 Beenen LF, Lindeboom J, Kasteleijn-Nolst DGTrenite, Heimans JJ, Snoek FJ, Touw DJ. 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 (04) 474-480.
  CrossrefPubMedGoogle Scholar
• 9 Bleck TP. Convulsive disorders: status epilepticus. Clin Neuropharmacol 1991; 14 (03) 191-198.
  CrossrefPubMedGoogle Scholar
• 10 Braestrup C, Nielsen M, Squires RF, Laurberg S. Benzodiazepine receptor in brain. Acta Psychiatr Scand Suppl 1978; 274: 27-32.
  Google Scholar
• 11 Burneo JG, Anandan JV, Barkley GL. A prospective study of the incidence of the purple glove syndrome. Epilepsia 2001; 42 (09) 1156-1159.
  PubMedGoogle Scholar
• 12 Calmeil LF. De l’epilepsie, étudies sous le rapport de son siege et de son influence sur la 13) Chen JW, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol 2006; 05 (03) 246-256.
  CrossrefPubMedGoogle Scholar
• 13 Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 2001; 57 (06) 1036-1042.
  CrossrefPubMedGoogle Scholar
• 14 Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002; 43 (02) 146-153.
  CrossrefPubMedGoogle Scholar
• 15 Claassen J, Hirsch LJ, Mayer SA. Treatment of status epilepticus: a survey of neurologists. J Neurol Sci 2003; 211 (1–2): 37-41.
  CrossrefPubMedGoogle Scholar
• 16 Clark LP, Prout TP. Status epilepticus: a clinical and pathological study in epilepsy (part 2). American Journal of Insanity 1903; 60: 645-675.
  Google Scholar
• 17 Clark LP, Prout TP. Status epilepticus: a clinical and pathological study in epilepsy (part1). American Journal of Insanity 1903; 60: 291-306.
  Google Scholar
• 18 Clark LP, Prout TP. Status epilepticus: a clinical and pathological study in epilepsy (part 3). American Journal of Insanity 1904; 61: 81-108.
  Google Scholar
• 19 Cranford RE, Leppik IE, Patrick B, Anderson CB, Kostick B. Intravenous phenytoin in acute treatment of seizures. Neurology 1979; 29 (11) 1474-1479.
  CrossrefPubMedGoogle Scholar
• 20 Delorenzo RJ, Garnett LK, Towne AR, Waterhouse EJ, Boggs JG, Morton L. et al. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia 1999; 40 (02) 164-169.
  CrossrefPubMedGoogle Scholar
• 21 Delorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L. et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996; 46 (04) 1029-1035.
  CrossrefPubMedGoogle Scholar
• 22 Delorenzo RJ, Pellock JM, Towne AR, Boggs JG. Epidemiology of status epilepticus. J Clin Neurophysiol 1995; 12 (04) 316-325.
  CrossrefPubMedGoogle Scholar
• 23 Delorenzo RJ, Waterhouse EJ, Towne AR, Boggs JG, Ko D, DeLorenzo GA. et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 1998; 39 (08) 833-840.
  CrossrefPubMedGoogle Scholar
• 24 Embacher N, Karner E, Wanschitz J, Beer R, Trinka E. Acute encephalopathy after intravenous administration of valproate in non-convulsive status epilepticus. Eur J Neurol 2006; 13 (10) e5-e6.
  Google Scholar
• 25 Fujikawa DG. The temporal evolution of neuronal damage from pilocarpine-induced status epilepticus. Brain Res 1996; 725 (01) 11-22.
  CrossrefPubMedGoogle Scholar
• 26 Gastaut H. A propos d’une classification symptomatologique des états de mal epileptiques. In: Gastaut H, Roger J, Lob H. editors. Les états de mal epileptiques. Paris: Masson; 1967: 1-8.
  Google Scholar
• 27 Genton P, Semah F, Trinka E. Valproic acid in epilepsy : pregnancy-related issues. Drug Saf 2006; 29 (01) 1-21.
  CrossrefPubMedGoogle Scholar
• 28 Gerstner T, Busing D, Bell N, Longin E, Kasper JM, Klostermann W. et al. Valproic acid-induced pancreatitis: 16 new cases and a review of the literature. J Gastroenterol 2007; 42 (01) 39-48.
  PubMedGoogle Scholar
• 29 Gidal BE, Baltes E, Otoul C, Perucca E. Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. Epilepsy Res 2005; 64 (1–2): 1-11.
  CrossrefPubMedGoogle Scholar
• 30 Hirsch LJ. Brain monitoring: the next frontier of ICU monitoring. J Clin Neurophysiol 2004; 21 (05) 305-306.
  PubMedGoogle Scholar
• 31 Hirsch LJ. Continuous EEG monitoring in the intensive care unit: an overview. J Clin Neurophysiol 2004; 21 (05) 332-340.
  PubMedGoogle Scholar
• 32 Hirsch LJ, Kull LL. Continuous EEG monitoring in the intensive care unit. Am J Electroneurodiagnostic Technol 2004; 44 (03) 137-158.
  PubMedGoogle Scholar
• 33 Holtkamp M. The anaesthetic and intensive care of status epilepticus. Curr Opin Neurol 2007; 20 (02) 188-193.
  CrossrefPubMedGoogle Scholar
• 34 Holtkamp M, Masuhr F, Harms L, Einhaupl KM, Meierkord H, Buchheim K. The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists. J Neurol Neurosurg Psychiatry 2003; 74 (08) 1095-1099.
  CrossrefPubMedGoogle Scholar
• 35 Holtkamp M, Othman J, Buchheim K, Masuhr F, Schielke E, Meierkord H. A “malignant” variant of status epilepticus. Arch Neurol 2005; 62 (09) 1428-1431.
  CrossrefPubMedGoogle Scholar
• 36 Holtkamp M, Othman J, Buchheim K, Meierkord H. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry 2005; 76 (04) 534-539.
  CrossrefPubMedGoogle Scholar
• 37 Holtkamp M, Othman J, Buchheim K, Meierkord H. Diagnosis of psychogenic nonepileptic status epilepticus in the emergency setting. Neurology 2006; 66 (11) 1727-1729.
  CrossrefPubMedGoogle Scholar
• 38 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 (03) 215-221.
  CrossrefPubMedGoogle Scholar
• 39 Howell SJ, Owen L, Chadwick DW. Pseudostatus epilepticus. QJ Med 1989; 71 (266) 507-519.
  Google Scholar
• 40 Hussein Z, Mukherjee D, Lamm J, Cavanaugh JH, Granneman GR. Pharmacokinetics of valproate after multiple-dose oral and intravenous infusion administration: gastrointestinal-related diurnal variation. J Clin Pharmacol 1994; 34 (07) 754-759.
  CrossrefPubMedGoogle Scholar
• 41 Hussein Z, Patterson KJ, Lamm JE, Cavanaugh JH, Granneman GR. Effect of infusion duration on valproate pharmacokinetics. Biopharm Drug Dispos 1993; 14 (05) 389-399.
  CrossrefPubMedGoogle Scholar
• 42 Jaitly R, Sgro JA, Towne AR, Ko D, Delorenzo RJ. Prognostic value of EEG monitoring after status epilepticus: a prospective adult study. J Clin Neurophysiol 1997; 14 (04) 326-334.
  CrossrefPubMedGoogle Scholar
• 43 Jallon P, Coeytaux A, Galobardes B, Morabia A. Incidence and case-fatality rate of status epilepticus in the Canton of Geneva. Lancet 1999; 353 (9163): 1496.
  PubMedGoogle Scholar
• 44 Jette N, Hirsch LJ. Continuous electroencephalogram monitoring in critically ill patients. Curr Neurol Neurosci Rep 2005; 05 (04) 312-321.
  CrossrefPubMedGoogle Scholar
• 45 Kalita J, Misra UK, Patel R. Initial EEG in status epilepticus is helpful in predicting seizure recurrence. Electromyogr Clin Neurophysiol 2006; 46 (03) 139-144.
  PubMedGoogle Scholar
• 46 Kalviainen R, Eriksson K, Parviainen I. Refractory generalised convulsive status epilepticus: a guide to treatment. CNS Drugs 2005; 19 (09) 759-768.
  CrossrefPubMedGoogle Scholar
• 47 Kapur J, Lothman EW, Delorenzo RJ. Loss of GABAA receptors during partial status epilepticus. Neurology 1994; 44 (12) 2407-2408.
  CrossrefPubMedGoogle Scholar
• 48 Kapur J, Macdonald RL. Rapid seizure-induced reduction of benzodiazepine and Zn²+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci 1997; 17 (19) 7532-7540.
  CrossrefPubMedGoogle Scholar
• 49 Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A. et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 2001; 42 (06) 714-718.
  CrossrefPubMedGoogle Scholar
• 50 Knapp LE, Kugler AR. Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy. J Child Neurol 1998; 13 (Suppl. 01) S15-S18.
  CrossrefPubMedGoogle Scholar
• 51 Konig SA, Schenk M, Sick C, Holm E, Heubner C, Weiss A. 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 (07) 1036-1040.
  CrossrefPubMedGoogle Scholar
• 52 Konig SA, Siemes H, Blaker F, Boenigk E, GrossSelbeck G, Hanefeld F. et al. Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities. Epilepsia 1994; 35 (05) 1005-1015.
  CrossrefPubMedGoogle Scholar
• 53 Kramer G, Bergmann A, Deshpande LS, König S, Kurth C, Kurlemann G. et al. Current Place of Intravenous Valproic Acid in the Treatment of Generalized Tonic-Clonic Status Epilepticus. Aktuelle Neurologie 2005; 32 (05) 263-274.
  Article in Thieme ConnectGoogle Scholar
• 54 Krishnamurthy KB, Drislane FW. Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus. Epilepsia 1999; 40 (06) 759-762.
  CrossrefPubMedGoogle Scholar
• 55 Larch J, Trinka E. Intravenous Valproate in Status Epilepticus. A systematic Review of the Evidence. Epilepsia 2006; 39: 47.
  Google Scholar
• 56 Leppik IE, Derivan AT, Homan RW, Walker J, Ramsay RE, Patrick B. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983; 249 (11) 1452-1454.
  CrossrefPubMedGoogle Scholar
• 57 Leppik IE, Patrick BK, Cranford RE. Treatment of acute seizures and status epilepticus with intravenous phenytoin. Adv Neurol 1983; 34: 447-451.
  Google Scholar
• 58 Limdi NA, Faught E. The safety of rapid valproic acid infusion. Epilepsia 2000; 41 (10) 1342-1345.
  CrossrefPubMedGoogle Scholar
• 59 Limdi NA, Knowlton RK, Cofield SS, Ver LWHoef, Paige AL, Dutta S. et al. Safety of rapid intravenous loading of valproate. Epilepsia 2007; 48 (03) 478-483.
  CrossrefPubMedGoogle Scholar
• 60 Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 2005; 64 (02) 353-355.
  CrossrefPubMedGoogle Scholar
• 61 Lothman EW, Bertram EH, Kapur J, Stringer JL. Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus. Epilepsy Res 1990; 06 (02) 110-118.
  CrossrefPubMedGoogle Scholar
• 62 Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology 1993; 43 (3 Pt 1): 483-488.
  CrossrefPubMedGoogle Scholar
• 63 Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998; 338 (14) 970-976.
  CrossrefPubMedGoogle Scholar
• 64 Lowenstein DH, Aminoff MJ. Clinical and EEG features of status epilepticus in comatose patients. Neurology 1992; 42 (01) 100-104.
  CrossrefPubMedGoogle Scholar
• 65 Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia 1999; 40 (01) 120-122.
  CrossrefPubMedGoogle Scholar
• 66 Luders HO, Rona S, Rosenow F, Arnold S, Carreno M, Diehl B. et al. A semiological classification of status epilepticus. Epileptic Disord 2005; 07 (02) 149-150.
  Google Scholar
• 67 Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ, Fitzsimmons BF. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002; 59 (02) 205-210.
  CrossrefPubMedGoogle Scholar
• 68 Mazarati AM, Baldwin R, Klitgaard H, Matagne A, Wasterlain CG. Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combinations in experimental status epilepticus. Epilepsy Res 2004; 58 (2–3): 167-174.
  CrossrefPubMedGoogle Scholar
• 69 Mazarati AM, Baldwin RA, Sankar R, Wasterlain CG. Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of selfsustaining status epilepticus. Brain Res 1998; 814 (1–2): 179-185.
  CrossrefPubMedGoogle Scholar
• 70 Mazarati AM, Wasterlain CG, Sankar R, Shin D. Self-sustaining status epilepticus after brief electrical stimulation of the perforant path. Brain Res 1998; 801 (1–2): 251-253.
  CrossrefPubMedGoogle Scholar
• 71 McLean MJ, Macdonald RL. Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther 1988; 244 (02) 789-795.
  PubMedGoogle Scholar
• 72 Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P. et al. EFNS guideline on the management of status epilepticus. Eur J Neurol 2006; 13 (05) 445-450.
  CrossrefPubMedGoogle Scholar
• 73 Meldrum BS. The revised operational definition of generalised tonic-clonic (TC) status epilepticus in adults. Epilepsia 1999; 40 (01) 123-124.
  CrossrefPubMedGoogle Scholar
• 74 Minicucci F, Muscas G, Perucca E, Capovilla G, Vigevano F, Tinuper P. Treatment of status epilepticus in adults: guidelines of the italian league against epilepsy. Epilepsia 2006; 47 (Suppl. 05) 9-15.
  PubMedGoogle Scholar
• 75 Misra UK, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology 2006; 67 (02) 340-342.
  CrossrefPubMedGoogle Scholar
• 76 Mohler H, Okada T. Benzodiazepine receptor: demonstration in the central nervous system. Science 1977; 198 (4319): 849-851.
  CrossrefPubMedGoogle Scholar
• 77 Naritoku DK, Mueed S. Intravenous loading of valproate for epilepsy. Clin Neuropharmacol 1999; 22 (02) 102-106.
  CrossrefPubMedGoogle Scholar
• 78 Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci 2005; 25 (34) 7724-7733.
  CrossrefPubMedGoogle Scholar
• 79 Neville BG, Chin RF, Scott RC. Childhood convulsive status epilepticus: epidemiology, management and outcome. Acta Neurol Scand 2007; 115 (04) 21-24.
  PubMedGoogle Scholar
• 80 Niermeijer JM, Uiterwaal CS, Van Donselaar CA. Propofol in status epilepticus: little evidence, many dangers?. J Neurol 2003; 250 (10) 1237-1240.
  CrossrefPubMedGoogle Scholar
• 81 O’Brien TJ, Cascino GD, So EL, Hanna DR. Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin. Neurology 1998; 51 (04) 1034-1039.
  CrossrefPubMedGoogle Scholar
• 82 Otoul C, Arrigo C, van Rijckevorsel K, French JA. Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy. Clin Neuropharmacol 2005; 28 (02) 72-78.
  CrossrefPubMedGoogle Scholar
• 83 Pandian JD, Cascino GD, So EL, Manno E, Fulgham JR. Digital video-electroencephalographic monitoring in the neurological-neurosurgical intensive care unit: clinical features and outcome. Arch Neurol 2004; 61 (07) 1090-1094.
  CrossrefPubMedGoogle Scholar
• 84 Parviainen I, Uusaro A, Kalviainen R, Kaukanen E, Mervaala E, Ruokonen E. High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit. Neurology 2002; 59 (08) 1249-1251.
  CrossrefPubMedGoogle Scholar
• 85 Parviainen I, Uusaro A, Kalviainen R, Mervaala E, Ruokonen E. Propofol in the treatment of refractory status epilepticus. Intensive Care Med 2006; 32 (07) 1075-1079.
  CrossrefPubMedGoogle Scholar
• 86 Patel NC, Landan IR, Levin J, Szaflarski J, Wilner AN. The use of levetiracetam in refractory status epilepticus. Seizure 2006; 15 (03) 137-141.
  CrossrefPubMedGoogle Scholar
• 87 Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 2004; 43 (11) 707-724.
  CrossrefPubMedGoogle Scholar
• 88 Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 2002; 16 (10) 695-714.
  CrossrefPubMedGoogle Scholar
• 89 Prasad K, Al Roomi K, Krishnan PR, Sequeira R. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev 2005; (04) CD003723.
  PubMedGoogle Scholar
• 90 Ramsay RE, Cantrell D, Collins SD, Walch JK, Naritoku DK, Cloyd JC. et al. Safety and tolerance of rapidly infused Depacon. A randomized trial in subjects with epilepsy. Epilepsy Res 2003; 52 (03) 189-201.
  CrossrefPubMedGoogle Scholar
• 91 Rosenow F, Arzimanoglou A, Baulac M. Recent developments in treatment of status epilepticus: a review. Epileptic Disord 2002; 04 (Suppl. 02) S41-S51.
  Google Scholar
• 92 Rosenow F, Trinka E. Status Epilepticus. In: Sitzer M, v. Stuckrad-Barre S, Schmutzhard E. editors. Neurologische Notfallund Intensivmedizin. München, Jena: Elsevier Urban und Fischer, 2004: 197-202.
  Google Scholar
• 93 Rossetti AO. Which anaesthetic should be used in the treatment of refractory status epilepticus?. Epilepsia. In press.
  Google Scholar
• 94 Rossetti AO, Bromfield EB. Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes. Eur Neurol 2005; 54 (01) 34-38.
  CrossrefPubMedGoogle Scholar
• 95 Rossetti AO, Bromfield EB. Determinants of success in the use of oral levetiracetam in status epilepticus. Epilepsy Behav 2006; 08 (03) 651-654.
  CrossrefPubMedGoogle Scholar
• 96 Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005; 62 (11) 1698-1702.
  CrossrefPubMedGoogle Scholar
• 97 Rupprecht S, Franke K, Fitzek S, Witte OW, Hagemann G. Levetiracetam as a treatment option in non-convulsive status epilepticus. Epilepsy Res 2007; 73 (03) 238-244.
  CrossrefPubMedGoogle Scholar
• 98 Scheffner D, Konig S, Rauterberg-Ruland I, Kochen W, Hofmann WJ, Unkelbach S. Fatal liver failure in 16 children with valproate therapy. Epilepsia 1988; 29 (05) 530-542.
  CrossrefPubMedGoogle Scholar
• 99 Schulze-Bonhage A, Hefft S, Oehl B. Termination of complex partial status epilepticus by intravenous levetiracetam–a case report. J Neurol Neurosurg Psychiatry published online 12 mar. 2007 doi: 10.1136/jnnp.2006113951.
  PubMedGoogle Scholar
• 100 Shaner DM, McCurdy SA, Herring MO, Gabor AJ. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology 1988; 38 (02) 202-207.
  CrossrefPubMedGoogle Scholar
• 101 Shorvon S. Status Epilepticus – Its clinical features and treatment in children and adults. Cambridge: Cambridge University Press; 1994
  Google Scholar
• 102 Shorvon S. The classification of status epilepticus. Epileptic Disord 2005; 07 (01) 1-3.
  Google Scholar
• 103 Shorvon S, Trinka E, Walker M. First London Colloquium on Status Epilepticus. Epilepsia. In press.
  Google Scholar
• 104 Sinha S, Naritoku DK. Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology 2000; 55 (05) 722-724.
  CrossrefPubMedGoogle Scholar
• 105 Suter C, Brush J. Clinical problems of brain death and coma in intensive care units. Ann NY Acad Sci 1978; 315: 398-416.
  CrossrefPubMedGoogle Scholar
• 106 Teich M, Longin E, Dempfle CE, Konig S. Factor XIII deficiency associated with valproate treatment. Epilepsia 2004; 45 (02) 187-189.
  CrossrefPubMedGoogle Scholar
• 107 Temkin O. The falling sickness. The Johns Hopkins University Press; 1971
  Google Scholar
• 108 Theodore WH, Porter RJ, Albert P, Kelley K, Bromfield E, Devinsky O. et al. The secondarily generalized tonic-clonic seizure:a videotape analysis. Neurology 1994; 44 (08) 1403-1407.
  CrossrefPubMedGoogle Scholar
• 109 Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ. 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 (12) 792-798.
  CrossrefPubMedGoogle Scholar
• 110 Trinka E. The Use of Valproate and New Antiepileptic Drugs in Status Epilepticus. Epilepsia. In press.
  Google Scholar
• 111 Uberall MA, Trollmann R, Wunsiedler U, Wenzel D. Intravenous valproate in pediatric epilepsy patients with refractory status epilepticus. Neurology 2000; 54 (11) 2188-2189.
  PubMedGoogle Scholar
• 112 Ulvi H, Yoldas T, Mungen B, Yigiter R. Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus. Neurol Sci 2002; 23 (04) 177-182.
  CrossrefPubMedGoogle Scholar
• 113 van Rijckevorsel K, Boon P, Hauman H, Legros B, Ossemanns M, Sadzot B. et al. Standards of care for adults with convulsive status epilepticus: Belgian consensus recommendations. Acta Neurol Belg 2005; 105 (03) 111-118.
  PubMedGoogle Scholar
• 114 Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome. Intensive Care Med 2003; 29 (09) 1417-1425.
  CrossrefPubMedGoogle Scholar
• 115 Venkataraman V, Wheless JW. Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients. Epilepsy Res 1999; 35 (02) 147-153.
  CrossrefPubMedGoogle Scholar
• 116 Walker M, Cross H, Smith S, Young C, Aicardi J, Appleton R. et al. Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports. Epileptic Disord 2005; 07 (03) 253-296.
  Google Scholar
• 117 Walker MC, Howard RS, Smith SJ, Miller DH, Shorvon SD, Hirsch NP. Diagnosis and treatment of status epilepticus on a neurological intensive care unit. QJM 1996; 89 (12) 913-920.
  CrossrefPubMedGoogle Scholar
• 118 Walker MC, Smith SJ, Shorvon SD. The intensive care treatment of convulsive status epilepticus in the UK. Results of a national survey and recommendations. Anaesthesia 1995; 50 (02) 130-135.
  CrossrefPubMedGoogle Scholar
• 119 Walton NY, Treiman DM. Response of status epilepticus induced by lithium and pilocarpine to treatment with diazepam. Exp Neurol 1988; 101 (02) 267-275.
  CrossrefPubMedGoogle Scholar
• 120 Walton NY, Treiman DM. Valproic acid treatment of experimental status epilepticus. Epilepsy Res 1992; 12 (03) 199-205.
  CrossrefPubMedGoogle Scholar
• 121 Ward MM, Barbaro NM, Laxer KD, Rampil IJ. Preoperative valproate administration does not increase blood loss during temporal lobectomy. Epilepsia 1996; 37 (01) 98-101.
  PubMedGoogle Scholar
• 122 Wheless JW, Vazquez BR, Kanner AM, Ramsay RE, Morton L, Pellock JM. Rapid infusion with valproate sodium is well tolerated in patients with epilepsy. Neurology 2004; 63 (08) 1507-1508.
  CrossrefPubMedGoogle Scholar
• 123 Wilder BJ, Campbell K, Ramsay RE, Garnett WR, Pellock JM, Henkin SA. et al. Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery. Arch Neurol 1996; 53 (08) 764-768.
  CrossrefPubMedGoogle Scholar
• 124 Wilder BJ, Ramsay RE, Willmore LJ, Feussner GF, Perchalski RJ, Shumate Jr JB. Efficacy of intravenous phenytoin in the treatment of status epilepticus: kinetics of central nervous system penetration. Ann Neurol 1977; 01 (06) 511-518.
  CrossrefPubMedGoogle Scholar
• 125 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 (02) 185-198.
  CrossrefPubMedGoogle Scholar
• 126 Wittman Jr JJ, Hirsch LJ. Continuous electroencephalogram monitoring in the critically ill. Neurocrit Care 2005; 02 (03) 330-341.
  CrossrefPubMedGoogle Scholar
• 127 Zaccara G, Franciotta D, Perucca E. Idiosyncratic Adverse Reactions to Antiepileptic Drugs. Epilepsia 2007; 48 (07) 1223-1244.
  CrossrefPubMedGoogle Scholar