Dokument: Pharmakologische Therapie des Anfallsstatus und der Anfallsserie mit dem Antikonvulsivum Levetirazetam. Eine Beobachtungsstudie aus der Neurologischen Klinik des Universitätsklinikums Düsseldorf.

Titel:

Pharmakologische Therapie des Anfallsstatus und der Anfallsserie mit dem Antikonvulsivum Levetirazetam. Eine Beobachtungsstudie aus der Neurologischen Klinik des Universitätsklinikums Düsseldorf.

URL für Lesezeichen:

https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=19190

URN (NBN):

urn:nbn:de:hbz:061-20110913-104526-5

Kollektion:

Dissertationen

Sprache:

Deutsch

Dokumententyp:

Wissenschaftliche Abschlussarbeiten » Dissertation

Medientyp:

Text

Autor:

Krämer, Karolina [Autor]

Dateien:

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Dateien vom 12.09.2011 / geändert 12.09.2011

Beitragende:

Prof. Dr. med. Seitz, Rüdiger J. [Gutachter]
P.D. Dr. Steiner, Stephan [Gutachter]
Prof. Dr. Germing, Ulrich [Gutachter]

Dewey Dezimal-Klassifikation:

600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit

Beschreibung:

Ein Anfallsstatus stellt einen neurologischen Notfall dar und erfordert sofortige und effektive Therapie.
Diese Untersuchung an 25 Patienten, die im UKD vom 1. April 2007 bis zum 31. März 2008 behandelt wurden, zeigte, dass die Therapie am UKD mit 92% durchbrochener Anfallsstatus und Anfallsserien und 86% Anfallsfreiheit innerhalb der ersten 14. Tage effektiv und sicher war. Die Mortalität von 8% lag in dieser Untersuchung im unteren Durchschnittsbereich publizierter Studien. Die häufigsten Medikamente neben Levetirazetam (LEV) und Valproat (VPA) waren Benzodiazepine, vor allem Clonazepam.
Intravenös appliziertes LEV und VPA erwiesen sich als effektiv (Erfolgsrate von 67% bzw. 60%), gut verträglich und sicher in der Anwendung. LEV wurde häufiger als orale Dauermedikation weitergeführt als VPA (80% vs. 60%). Die Erfolgsraten sowohl von LEV als auch von VPA i.v. lagen in dieser Untersuchung etwas unterhalb des Durchschnitts, der in früheren Studien erzielt wurde. Dies könnte an dem relativ kleinen, teilweise neurochirurgischen Patientenkollektiv liegen. Um Levetirazetam und auch Valproat als Medikamente zur Therapie des Anfallsstatus bezüglich Effektivität und Sicherheit, aber auch im Verlauf der Therapie, besser beurteilen zu können, bedarf es daher kontrollierten, prospektiven Studien mit größeren Patientenkollektiven.
Aufgrund der Ergebnisse dieser Untersuchung erscheint intravenös appliziertes Levetirazetam als sicheres und effektives Medikament zur Akuttherapie des Anfallsstatus und der Anfallsserie vergleichbar der oralen Applikationsform zur Anfallsprophylaxe im stationären und ambulanten Bereich. Hinsichtlich der Effektivität könnte Levetirazetam Valproat leicht überlegen sein.

Quelle:

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1. Autorengruppe unter der Leitung von: Elger CE. Leitlinien der DGN- Erster epileptischer Anfall und Epilepsien im Erwachsenenalter. www.dgn.org: Deutsche Gesellschaft für Neurologie, 2008.
2. Chin R, Neville B, Scott R. A systematic review of the epidemiology of status epilepticus. Eur J Neurol 2004;11(12):800-10.
3. Sokic D, Jankovic S, Vojvodic N, Ristic A. Etiology of a short-term mortality in the group of 750 patients with 920 episodes of status epilepticus within a period of 10 years (1988-1997). Seizure 2009;18(3):215-9.
4. Treiman D, Meyers P, Walton N, Collins J, Colling C, Rowan A, 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):792-8.
5. Leppik I, Derivan A, Homan R, Walker J, Ramsay R, Patrick B. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983;249(11):1452-4.
6. 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(9):631-7.
7. Knake S, Gruener J, Hattemer K, Klein K, Bauer S, Oertel W, et al. Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus. J Neurol Neurosurg Psychiatry 2008;79(5):588-9.
8. Möddel G, Bunten S, Dobis C, Kovac S, Dogan M, Fischera M, et al. Intravenous levetiracetam: a new treatment alternative for refractory status epilepticus. J Neurol Neurosurg Psychiatry 2009;80(6):689-92.
9. Aiguabella M, Falip M, Villanueva V, de la Peña P, Molins A, Garcia-Morales I, et al. Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: a multicentric observational study. Seizure 2011;20(1):60-4.
10. Gámez-Leyva G, Aristín J, Fernández E, Pascual J. Experience with intravenous levetiracetam in status epilepticus: a retrospective case series. CNS Drugs 2009;23(11):983-7.
11. Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 2005;64(2):353-5.
12. Rüegg S, Naegelin Y, Hardmeier M, Winkler DT, Marsch S, Fuhr P. Intravenous levetiracetam: treatment experience with the first 50 critically ill patients. Epilepsy Behav 2008;12(3):477-80.
13. Lowenstein D. Treatment options for status epilepticus. Curr Opin Pharmacol 2005;5(3):334-9.
14. M AudLvK. Leitlinien der DGN-Status epilepticus im Erwachsenenalter. www.dgn.org: Deutsche Gesellschaft für Neurologie, 2008.
15. Mumenthaler M, Mattle H. Neurologie. 12. Auflage ed: Georg Thieme Verlag, 2008.
16. Masuhr K-F, Neumann M. Neurologie. Stuttgart: Thieme, 2007.
17. Serles W BC, Baumhackl U, Feucht M, Gruber-Sedlmayr U, Körner E, Ladurner G, Laich E, Rumpl E, Trinka E. Behandlung des akuten epileptischen Anfalls; repetitiver Anfälle und des Status epilepticus: Österreichische Sektion der Internationalen Liga gegen Epilepsie, 2002.
18. Knake S, Rosenow F, Vescovi M, Oertel W, Mueller H, Wirbatz A, et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 2001;42(6):714-8.
19. Hesdorffer D, Logroscino G, Cascino G, Annegers J, Hauser W. Incidence of status epilepticus in Rochester, Minnesota, 1965-1984. Neurology 1998;50(3):735-41.
20. Coeytaux A, Jallon P, Galobardes B, Morabia A. Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR). Neurology 2000;55(5):693-7.
21. Martinez C, Sullivan T, Hauser W. Prevalence of acute repetitive seizures (ARS) in the United Kingdom. Epilepsy Res 2009;87(2-3):137-43.
22. Proposal for Revised Clinical and Classification of Epileptic Seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1981;22:489-501.
23. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 1993;34(4):592-6.
24. Goldenberg M. Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. P T 2010;35(7):392-415.
25. DeLorenzo R, Pellock J, Towne A, Boggs J. Epidemiology of status epilepticus. J Clin Neurophysiol 1995;12(4):316-25.
26. Knake S, Hamer H, Rosenow F. Status epilepticus: a critical review. Epilepsy Behav 2009;15(1):10-4.
27. Lowenstein D. Status epilepticus: an overview of the clinical problem. Epilepsia 1999;40 Suppl 1:S3-8; discussion S21-2.
28. Behrouz R, Chen S, Tatum Wt. Evaluation and management of status epilepticus in the neurological intensive care unit. J Am Osteopath Assoc 2009;109(4):237-45.
29. Feen E, Bershad E, Suarez J. Status epilepticus. South Med J 2008;101(4):400-6.
30. Vignatelli L, Tonon C, D'Alessandro R, Epilepticus BGftSoS. Incidence and short-term prognosis of status epilepticus in adults in Bologna, Italy. Epilepsia 2003;44(7):964-8.
31. Tatum IV W, French J, Benbadis S, Kaplan P. The Etiology and Diagnosis of Status Epilepticus. Epilepsy Behav 2001;2(4):311-17.
32. Bösebeck F, Möddel G, Anneken K, Fischera M, Evers S, Ringelstein E, et al. [Refractory status epilepticus: diagnosis, therapy, course, and prognosis]. Nervenarzt 2006;77(10):1159-60, 62-4, 66-75.
33. Engelborghs S, D'Hooge R, De Deyn PP. Pathophysiology of epilepsy. Acta Neurol Belg 2000;100(4):201-13.
34. De Deyn PP, D'Hooge R, Marescau B, Pei YQ. Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. Epilepsy Res 1992;12(2):87-110.
35. Beghi E, De Maria G, Gobbi G, Veneselli E. Diagnosis and treatment of the first epileptic seizure: guidelines of the Italian League against Epilepsy. Epilepsia 2006;47 Suppl 5:2-8.
36. Meierkord H, Boon P, Engelsen B, Göcke K, Shorvon S, Tinuper P, et al. EFNS guideline on the management of status epilepticus in adults. Eur J Neurol 2010;17(3):348-55.
37. Schwarz S, Schwab S, Hacke W. [Status epilepticus. Rational diagnosis and current therapeutic concepts]. Anaesthesist 1999;48(7):455-64.
38. Kohrman M. What is epilepsy? Clinical perspectives in the diagnosis and treatment. J Clin Neurophysiol 2007;24(2):87-95.
39. St Louis E. Monotherapy to polytherapy: antiepileptic drug conversions through the spectrum of epilepsy care. Curr Neuropharmacol 2009;7(2):75-6.
40. Gilad R, Izkovitz N, Dabby R, Rapoport A, Sadeh M, Weller B, et al. Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin. Acta Neurol Scand 2008;118(5):296-300.
41. Singh A, Le Morvan P. Treatment of status epilepticus with intravenous clonazepam. Prog Neuropsychopharmacol Biol Psychiatry 1982;6(4-6):539-42.
42. Congdon P, Forsythe W. Intravenous clonazepam in the treatment of status epilepticus in children. Epilepsia 1980;21(1):97-102.
43. Misra U, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology 2006;67(2):340-2.
44. Pharma U. Fachinformation (Zusammenfassung der Merkmale des Arzneimittels/SPC), Keppra 100mg/ml Konzentrat zur Herstellung einer Infusionslösung. www.ucb.de: UCB Pharma SA, 2010.
45. UCB Pharma GmbH G. 2011.
46. Cereghino J, Biton V, Abou-Khalil B, Dreifuss F, Gauer L, Leppik I. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology 2000;55(2):236-42.
47. Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia 2000;41(10):1276-83.
48. Shorvon S, Löwenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia 2000;41(9):1179-86.
49. Kuba R, Novotná I, Brázdil M, Kocvarová J, Tyrlíková I, Mastík J, et al. Long-term levetiracetam treatment in patients with epilepsy: 3-year follow up. Acta Neurol Scand 2010;121(2):83-8.
50. Kwan P, Lim S, Chinvarun Y, Cabral-Lim L, Aziz Z, Lo Y, et al. Efficacy and safety of levetiracetam as adjunctive therapy in adult patients with uncontrolled partial epilepsy: the Asia SKATE II Study. Epilepsy Behav 2010;18(1-2):100-5.
51. Wu T, Chen C, Chen T, Tseng Y, Chiang C, Hung C, et al. Clinical efficacy and cognitive and neuropsychological effects of levetiracetam in epilepsy: an open-label multicenter study. Epilepsy Behav 2009;16(3):468-74.
52. Ramael S, Daoust A, Otoul C, Toublanc N, Troenaru M, Lu Z, et al. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia 2006;47(7):1128-35.
53. Cereghino J. Identification and treatment of acute repetitive seizures in children and adults. Curr Treat Options Neurol 2007;9(4):249-55.
54. Patsalos P. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther 2000;85(2):77-85.
55. Surges R, Volynski K, Walker M. Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilpsy revisited. Therapeutic Advances in Neurological Disorders 2008;1(1):13-24.
56. Lynch B, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh S, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A 2004;101(26):9861-6.
57. Nagarkatti N, Deshpande L, DeLorenzo R. Levetiracetam inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture. Neurosci Lett 2008;436(3):289-93.
58. Zona C, Niespodziany I, Marchetti C, Klitgaard H, Bernardi G, Margineanu D. Levetiracetam does not modulate neuronal voltage-gated Na+ and T-type Ca2+ currents. Seizure 2001;10(4):279-86.
59. Rigo J, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, et al. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol 2002;136(5):659-72.
60. Vigevano F. Levetiracetam in pediatrics. J Child Neurol 2005;20(2):87-93.
61. Pisani A, Bonsi P, Martella G, De Persis C, Costa C, Pisani F, et al. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia 2004;45(7):719-28.
62. Niespodziany I, Klitgaard H, Margineanu D. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci Lett 2001;306(1-2):5-8.
63. Lukyanetz E, Shkryl V, Kostyuk P. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia 2002;43(1):9-18.
64. Yang X, Weisenfeld A, Rothman S. Prolonged exposure to levetiracetam reveals a presynaptic effect on neurotransmission. Epilepsia 2007;48(10):1861-9.
65. Carunchio I, Pieri M, Ciotti M, Albo F, Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia 2007;48(4):654-62.
66. Lee C, Lee C, Tsai T, Liou H. PKA-mediated phosphorylation is a novel mechanism for levetiracetam, an antiepileptic drug, activating ROMK1 channels. Biochem Pharmacol 2008;76(2):225-35.
67. Kuzniecky R, Pan J, Burns A, Devinsky O, Hetherington H. Levetiracetam has no acute effects on brain gamma-aminobutyric acid levels. Epilepsy Behav 2008;12(2):242-4.
68. van Vliet E, Aronica E, Redeker S, Boer K, Gorter J. Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy. Epilepsia 2009;50(3):422-33.
69. Custer K, Austin N, Sullivan J, Bajjalieh S. Synaptic vesicle protein 2 enhances release probability at quiescent synapses. J Neurosci 2006;26(4):1303-13.
70. Janz R, Goda Y, Geppert M, Missler M, Südhof T. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron 1999;24(4):1003-16.
71. Kaminski R, Matagne A, Leclercq K, Gillard M, Michel P, Kenda B, et al. SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy. Neuropharmacology 2008;54(4):715-20.
72. Radtke R. Pharmacokinetics of levetiracetam. Epilepsia 2001;42 Suppl 4:24-7.
73. Ramael S, De Smedt F, Toublanc N, Otoul C, Boulanger P, Riethuisen J, et al. Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects. Clin Ther 2006;28(5):734-44.
74. Wirtz M. Deskriptive Statistik. In: Nachtigall C, editor. Statistische Methoden für Psychologen. Weinheim & München: Juventa Verlag, 2006:91-92.
75. Nachtigall C. Wahrscheinlichkeitsrechnung und Inferenzstatistik. In: Wirtz M, editor. Statistische Methoden für Psychologen Teil 2. Weinheim & München: Juventa Verlag, 2006:206.
76. Uges J, van Huizen M, Engelsman J, Wilms E, Touw D, Peeters E, et al. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus. Epilepsia 2009;50(3):415-21.
77. Berning S, Boesebeck F, van Baalen A, Kellinghaus C. Intravenous levetiracetam as treatment for status epilepticus. J Neurol 2009;256(10):1634-42.
78. Olsen KB, Taubøll E, Gjerstad L. Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults. Acta Neurol Scand Suppl 2007;187:51-4.

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47. Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia 2000;41(10):1276-83.
48. Shorvon S, Löwenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia 2000;41(9):1179-86.
49. Kuba R, Novotná I, Brázdil M, Kocvarová J, Tyrlíková I, Mastík J, et al. Long-term levetiracetam treatment in patients with epilepsy: 3-year follow up. Acta Neurol Scand 2010;121(2):83-8.
50. Kwan P, Lim S, Chinvarun Y, Cabral-Lim L, Aziz Z, Lo Y, et al. Efficacy and safety of levetiracetam as adjunctive therapy in adult patients with uncontrolled partial epilepsy: the Asia SKATE II Study. Epilepsy Behav 2010;18(1-2):100-5.
51. Wu T, Chen C, Chen T, Tseng Y, Chiang C, Hung C, et al. Clinical efficacy and cognitive and neuropsychological effects of levetiracetam in epilepsy: an open-label multicenter study. Epilepsy Behav 2009;16(3):468-74.
52. Ramael S, Daoust A, Otoul C, Toublanc N, Troenaru M, Lu Z, et al. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia 2006;47(7):1128-35.
53. Cereghino J. Identification and treatment of acute repetitive seizures in children and adults. Curr Treat Options Neurol 2007;9(4):249-55.
54. Patsalos P. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther 2000;85(2):77-85.
55. Surges R, Volynski K, Walker M. Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilpsy revisited. Therapeutic Advances in Neurological Disorders 2008;1(1):13-24.
56. Lynch B, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh S, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A 2004;101(26):9861-6.
57. Nagarkatti N, Deshpande L, DeLorenzo R. Levetiracetam inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture. Neurosci Lett 2008;436(3):289-93.
58. Zona C, Niespodziany I, Marchetti C, Klitgaard H, Bernardi G, Margineanu D. Levetiracetam does not modulate neuronal voltage-gated Na+ and T-type Ca2+ currents. Seizure 2001;10(4):279-86.
59. Rigo J, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, et al. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol 2002;136(5):659-72.
60. Vigevano F. Levetiracetam in pediatrics. J Child Neurol 2005;20(2):87-93.
61. Pisani A, Bonsi P, Martella G, De Persis C, Costa C, Pisani F, et al. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia 2004;45(7):719-28.
62. Niespodziany I, Klitgaard H, Margineanu D. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci Lett 2001;306(1-2):5-8.
63. Lukyanetz E, Shkryl V, Kostyuk P. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia 2002;43(1):9-18.
64. Yang X, Weisenfeld A, Rothman S. Prolonged exposure to levetiracetam reveals a presynaptic effect on neurotransmission. Epilepsia 2007;48(10):1861-9.
65. Carunchio I, Pieri M, Ciotti M, Albo F, Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia 2007;48(4):654-62.
66. Lee C, Lee C, Tsai T, Liou H. PKA-mediated phosphorylation is a novel mechanism for levetiracetam, an antiepileptic drug, activating ROMK1 channels. Biochem Pharmacol 2008;76(2):225-35.
67. Kuzniecky R, Pan J, Burns A, Devinsky O, Hetherington H. Levetiracetam has no acute effects on brain gamma-aminobutyric acid levels. Epilepsy Behav 2008;12(2):242-4.
68. van Vliet E, Aronica E, Redeker S, Boer K, Gorter J. Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy. Epilepsia 2009;50(3):422-33.
69. Custer K, Austin N, Sullivan J, Bajjalieh S. Synaptic vesicle protein 2 enhances release probability at quiescent synapses. J Neurosci 2006;26(4):1303-13.
70. Janz R, Goda Y, Geppert M, Missler M, Südhof T. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron 1999;24(4):1003-16.
71. Kaminski R, Matagne A, Leclercq K, Gillard M, Michel P, Kenda B, et al. SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy. Neuropharmacology 2008;54(4):715-20.
72. Radtke R. Pharmacokinetics of levetiracetam. Epilepsia 2001;42 Suppl 4:24-7.
73. Ramael S, De Smedt F, Toublanc N, Otoul C, Boulanger P, Riethuisen J, et al. Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects. Clin Ther 2006;28(5):734-44.
74. Wirtz M. Deskriptive Statistik. In: Nachtigall C, editor. Statistische Methoden für Psychologen. Weinheim & München: Juventa Verlag, 2006:91-92.
75. Nachtigall C. Wahrscheinlichkeitsrechnung und Inferenzstatistik. In: Wirtz M, editor. Statistische Methoden für Psychologen Teil 2. Weinheim & München: Juventa Verlag, 2006:206.
76. Uges J, van Huizen M, Engelsman J, Wilms E, Touw D, Peeters E, et al. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus. Epilepsia 2009;50(3):415-21.
77. Berning S, Boesebeck F, van Baalen A, Kellinghaus C. Intravenous levetiracetam as treatment for status epilepticus. J Neurol 2009;256(10):1634-42.
78. Olsen KB, Taubøll E, Gjerstad L. Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults. Acta Neurol Scand Suppl 2007;187:51-4.

Lizenz:

Urheberrechtsschutz

Bezug:

November 2007- Juli 2011

Fachbereich / Einrichtung:

Medizinische Fakultät

Dokument erstellt am:

13.09.2011

Dateien geändert am:

13.09.2011

Promotionsantrag am:

10.03.2011

Datum der Promotion:

21.07.2011

Heinrich-Heine-Universität Düsseldorf

Dokument: Pharmakologische Therapie des Anfallsstatus und der Anfallsserie mit dem Antikonvulsivum Levetirazetam. Eine Beobachtungsstudie aus der Neurologischen Klinik des Universitätsklinikums Düsseldorf.