Definition der pharmakoresistenten Epilepsie: Konsensusvorschlag der ad hoc-Task Force der ILAE-Kommission für Therapeutische Strategien[1]

Zusammenfassung

Zur Verbesserung der Patientenversorgung und Förderung der klinischen Forschung hat die Internationale Liga gegen Epilepsie (ILAE) eine Task Force beauftragt, eine Konsensusdefinition der pharmakoresistenten Epilepsie zu erarbeiten. Der Gesamtrahmen der Definition hat 2 „hierarchische” Ebenen: Ebene 1 liefert ein allgemeines Schema zur Kategorisierung des Behandlungsergebnisses jeder therapeutischen Intervention, einschließlich eines minimal erforderlichen Datensatzes zur erfolgten Behandlung; Ebene 2 liefert anhand einer Reihe entscheidender Kriterien, die auf der Kategorisierung des Ansprechens auf Anwendungsversuche mit Antiepileptika (aus Ebene 1) beruhen, eine Kerndefinition der pharmakoresistenten Epilepsie. Als prüfbare Hypothese wird vorgeschlagen, eine pharmakoresistente Epilepsie als Versagen von 2 geeigneten Behandlungsversuchen mit vertragenen sowie angemessen ausgewählten und eingesetzten Antiepileptikaanwendungen (sei es als Mono- oder als Kombinationstherapie) zur Erzielung einer anhaltenden Anfallsfreiheit zu definieren. Diese Definition kann weiterentwickelt werden, wenn neue Daten verfügbar werden. Das Grundprinzip dieser Definition und die wichtigsten Regeln für ihre korrekte Anwendung werden diskutiert, und anhand von Beispielen wird die Anwendung der Definition in der klinischen Praxis veranschaulicht.

Abstract

To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two „hierarchical” levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.

Epilepsie - Pharmakoresistenz - refraktär - schwer behandelbar - Definition - Internationale Liga gegen Epilepsie

epilepsy - drug resistance - refractory - intractable - definition - international league against epilepsy

Literatur

• 1 Perucca E. Pharmacoresistance in epilepsy. How should it be defined?.  CNS Drugs. 1998;  10 171-179
• 2 Tanganelli P, Regesta G. Clinical aspects and biological bases of drug-resistant epilepsy.  Epilepsy Res. 1999;  34 109-122
• 3 Berg A T, Vickrey B G, Testa F M. et al . How long does it take epilepsy to become intractable? A prospective investigation.  Ann Neurol. 2006;  60 73-79
• 4 Kwan P, Brodie M J. Issues of medical intractability for surgical candidacy. In: Wyllie E, ed The Treatment of Epilepsy: Principles and Practice. 4th ed. Philadelphia; Lippincott Williams & Wilkins 2006: 983-991
• 5 Arzimanoglou A, Ryvlin P. Towards a clinically meaningful definition of drug-resistance. In: Kahane P, Berg A, Löscher W et al., eds Progress in Epileptic Disorder (Vol 7): Drug Resistant Epilepsies. Montrouge; John Libbey Eurotext 2008: 1-6
• 6 Kahane P, Berg A, Löscher W et al eds. Progress in Epileptic Disorder (Vol 7): Drug Resistant Epilepsies. Montrouge; John Libbey Eurotext 2008
• 7 Kwan P, Brodie M J. Effectiveness of first antiepileptic drug.  Epilepsia. 2001;  42 255-1260
• 8 World Health Organization Collaborating Centre for Drug Statistics Methodology .About the ATC / DDD system. Accessed December 1, 2008 at http:// http://www.whocc.no/atcddd/
• 9 Perucca E, Dulac O, Shorvon S. et al . Harnessing the clinical potential of antiepileptic drug therapy: dosage optimisation.  CNS Drugs. 2001;  15 609-621
• 10 Sillanpää M, Haataja L, Shinnar S. Perceived impact of childhoodonset epilepsy on quality of life as an adult.  Epilepsia. 2004;  45 971-977
• 11 Vickrey B G, Hays R D, Rausch R. et al . Outcomes in 248 patients who had diagnostic evaluations for epilepsy surgery.  Lancet. 1995;  346 1445-1449
• 12 Jacoby A, Gamble C, Doughty J. et al, Medical Research Council MESS Study Group . Quality of life outcomes of immediate or delayed treatment of early epilepsy and single seizures.  Neurology. 2007;  68 1188-1196
• 13 Téllez-Zenteno J F, Dhar R, Hernandez-Ronquillo L. et al . Long-term outcomes in epilepsy surgery: antiepileptic drugs, mortality, cognitive and psychosocial aspects.  Brain. 2007;  130 334-345
• 14 Hanley J A, Lippman-Hand A. If nothing goes wrong, is everything alright?.  JAMA. 1983;  259 1743-1745
• 15 Sillanpää M, Shinnar S. Obtaining a driver’s license and seizure relapse in patients with childhood-onset epilepsy.  Neurology. 2005;  64 680-686
• 16 Markand O N, Salanova V, Whelihan E. et al . Health-related quality of life outcome in medically refractory epilepsy treated with anterior temporal lobectomy.  Epilepsia. 2000;  41 749-759
• 17 Spencer S S, Berg A T, Vickrey B G. et al . Multicenter Study of Epilepsy Surgery. Health-related quality of life over time since resective epilepsy surgery.  Ann Neurol. 2007;  62 327-334
• 18 Jacoby A, Baker G A, Steen N. et al . The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. Community study.  Epilepsia. 1996;  37 148-161
• 19 Fisher R S, Parsonage M, Beaussart M. et al . Epilepsy and driving: an international perspective. Joint Commission on Drivers’ Licensing of the International Bureau for Epilepsy and the International League Against Epilepsy.  Epilepsia. 1994;  35 675-684
• 20 Berg A T, Engel Jr J. Restricted driving for people with epilepsy.  Neurology. 1999;  52 1306-1307
• 21 World Health Organization .International Drug Monitoring: the Role of National Centres. Techn Rep Series. Geneva; WHO 1972: 498
• 22 Leape L L. Preventing adverse drug events.  Am J Health Syst Pharm. 1995;  52 379-382
• 23 Edwards R I, Aronson J K. Adverse drug reactions: definitions, diagnosis, and management.  Lancet. 2000;  356 1255-1259
• 24 Baker G A, Camfield C, Camfield P. et al . Commission on Outcome Measurement in Epilepsy, 1994–1997: Final report.  Epilepsia. 1998;  39 213-231
• 25 Carreño M, Gil-Nagel A, Sanchez J C. et al . Strategies to detect adverse effects of antiepileptic drugs in clinical practice.  Epilepsy Behav. 2008;  13 178-183
• 26 Wild J M, Ahn H S, Baulac M. et al . Vigabatrin and epilepsy: lessons learned.  Epilepsia. 2007;  48 1318-1327
• 27 Karch F E, Lasagna L. Toward the operational identification of adverse drug reactions.  Clin Pharmacol Ther. 1977;  21 247-254
• 28 Leone M A, Beghi E, Righini C. et al . Epilepsy and quality of life in adults: a review of instruments.  Epilepsy Res. 2005;  66 23-44
• 29 Wass C T, Rajala M M, Hughes J M. et al . Long-term follow-up of patients treated surgically for medically intractable epilepsy: results in 191patients treated at Mayo Clinic Rochester between July 1972 and March 1985.  Mayo Clin Proc. 1996;  71 1105-1113
• 30 Wilson S J, Saling M M, Lawrence J. et al . Outcome of temporal lobectomy: expectations and the prediction of perceived success.  Epilepsy Res. 1999;  36 1-14
• 31 Reid K, Herbert A, Baker G A. Epilepsy surgery: patient perceived long-term costs and benefits.  Epilepsy Behav. 2004;  5 81-87
• 32 Chin P S, Berg A T, Spencer S S. et al . Patient-perceived impact of resective epilepsy surgery.  Neurology. 2006;  66 1882-1887
• 33 Berg A T, Levy S R, Testa F M. et al . Remission of epilepsy after 2 drug failures in children: a prospective study.  Ann Neurol. 2009;  65 510-519
• 34 Huttenlocher P R, Hapke R J. A follow-up study of intractable seizures in childhood.  Ann Neurol. 1990;  28 699-705
• 35 Berg A T, Shinnar S, Levy S R. et al . Early development of intractable epilepsy in children: a prospective study.  Neurology. 2001;  56 1445-1452
• 36 Callaghan B C, Anand K, Hesdorffer D. et al . Likelihood of seizure remission in an adult population with refractory epilepsy.  Ann Neurol. 2007;  62 382-389
• 37 Luciano A L, Shorvon S D. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy.  Ann Neurol. 2007;  62 375-381
• 38 Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs: effect of past treatment history.  Neurology. 2008;  70 54-65
• 39 Kwan P, Brodie M J. Early identification of refractory epilepsy.  N Engl J Med. 2000;  342 314-319
• 40 Mohanraj R, Brodie M J. Diagnosing refractory epilepsy: response to sequential treatment schedules.  Eur J Neurol. 2006;  13 277-282
• 41 Arts W F, Brouwer O F, Peters A C. et al . Course and prognosis of childhood epilepsy: 5-year follow-up of the Dutch study of epilepsy in childhood.  Brain. 2004;  127 1774-1784

1 Autorisierte Übersetzung von Dr. med. Günter Krämer, Medizinischer Direktor, Schweizerisches Epilepsie-Zentrum, Bleulerstr. 60, 8008 Zürich, Schweiz, Tel. [phone], E-Mail: [e-mail].
Zur Publikation angenommen am 20. September 2009, Original erschienen in Epilepsia 2010; 51: 1069–1077 sowie Erratum in Epilepsia 2010; 51: 1922.