Pharmakoresistente Epilepsien im Kindesalter

Zusammenfassung

Epilepsien gehören weltweit zu den häufigsten neurologischen Krankheiten. In 2/3 der Fälle manifestiert die Erkrankung vor dem 20. Lebensjahr und beeinflusst wesentlich die weitere Entwicklung. In 60–70 % wird mit Antiepileptika anhaltende Anfallsfreiheit erzielt, in 30–40 % treten jedoch trotz angemessener medikamentöser Behandlung weiter Anfälle in nicht akzeptabler Häufigkeit und/oder Schwere auf. Diese „pharmakoresistenten Epilepsien“ sind mit erhöhter Mortalität und chronischer Beeinträchtigung der Lebensqualität verbunden. Sie gehören deshalb weltweit zu den Erkrankungen mit den höchsten Belastungen für die Gesundheitssysteme.

Die frühzeitige zuverlässige Vorhersage zu erwartender Pharmakoresistenz sollte daher integraler Bestandteil eines umfassenden Behandlungsplanes sein, nicht zuletzt deshalb, da bei etwa 30 % der pharmakoresistenten PatientInnen nicht medikamentöse Therapieverfahren, insbesondere die Epilepsiechirurgie, eine effektive Alternative darstellen.

Die internationale Liga gegen Epilepsie (ILAE) hat 2010 einen konsensuellen Vorschlag zur Definition der Pharmakoresistenz erarbeitet, der das frühzeitige Erfassen therapieresistenter PatientInnen erleichtern soll. Das Grundprinzip dieser Definition und die wichtigsten Regeln für ihre korrekte Anwendung werden veranschaulicht.

Summary

Epilepsy is one of the most important chronic neurologic diseases, affecting a significant proportion of the population from childhood to old age. Although two of three patients become seizure-free with antiepileptic drugs, as many as 20–40 % do not respond to medical treatment. These so-called “pharmaco-resistant epilepsies” are associated with major socioeconomic consequences for the individual patient and for society. In addition, there is no doubt, that in a significant proportion of patients with pharmacoresistant epilepsies epilepsy surgery is several-fold more efficacious than continued medical treatment. Therefore, it is of great clinical interest to predict long-term seizure outcome as early as possible.

In 2010, the International League Against Epilepsy (ILAE) for the first time proposed a consensus definition of drug resistant epilepsy. The rationale behind the definition and the principles governing its proper use are explained.

Schlüsselwörter

Epilepsie - Pharmakoresistenz - ILAE-Definition

Keywords

Epilepsy - pharmacoresistance - ILAE-Definition

• Literatur

• 1 Aikia M, Kalviainen R, Mervaala E. et al Predictors of seizure outcome in newly diagnosed partial epilepsy: memory performance as a prognostic factor. Epilepsy Res 1999; 37: 159-167.
• 2 Arts WF, Geerts AT, Brouwer OF. et al The early prognosis of epilepsy in childhood: the prediction of poor outcome. The Dutch study of epilepsy in childhood. Epilepsia 1999; 40: 726-734.
• 3 Avanzini G. Is tolerance to antiepileptic drugs clinically relevant?. Epilepsia 2006; 47: 1285-1287.
• 4 Berg AT, Levy SR, Novotny EJ, Shinnar S. Predictors of intractable epilepsy in childhood: a case-controlled study. Epilepsia 1996; 37: 24-30.
• 5 Berg AT, Langfitt J, Shinnar S. et al How long does it take for partial epilepsy to become intractable?. Neurology 2003; 60: 186-190.
• 6 Berg AT. Defining intractable epilepsy. AdvNeurol 2006; 97: 5-10.
• 7 Beck H, Uebachs M. -Target“-Mechanismen der Pharmakoresistenz bei Epilepsiepatienten. Z Epileptol 2010; 23: 161-165.
• 8 Brorson LO, Wranne L. Long-term prognosis in childhood epilepsy: survival and seizure prognosis. Epilepsia 1987; 28: 324-330.
• 9 Camfield C, Camfield P, Gordon K, Smith B, Dooley J. Outcome of childhood epilepsy: a populationbased study with a simple predictive scoring system for those treated with medication. J Pediatr 122: 861-868. 1993;
• 10 Dlugos DJ, Samuel MD, Strom BL, Farrar JT. Response to first drug trial predicts outcome in childhood temporal lobe epilepsy. Neurology 2001; 57: 2259-2264.
• 11 Farrell K, Wirrell E, Whiting S. The definition and prediction of intractable epilepsy in children. AdvNeurol 2006; 97: 435-442.
• 12 Fisher RS, van Emde Boas W, Blume W. et al Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46: 470-472.
• 13 Gilliam FG, Fessler AJ, Baker G. et al Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology 2004; 62: 23-27.
• 14 Hauser WA. Incidence and prevalence. In Engel Jr J, Pedley TA. (eds). Epilepsy: A Comprehensive Textbook.. Philadelphia: Lippincott-Raven Publishers; 1997: 47-57.
• 15 Hauser WA, Rich SS, Lee JR. et al Risk of recurrent seizures after two unprovoked seizures. N Engl J Med 1998; 338: 429-434.
• 16 Hitiris N, Mohanraj R, Norrie J. et al Predictors of pharmacoresistant epilepsy. Epilepsy Res 2007; 75: 192-196.
• 17 Klepper J, Leiendecker B. Ketogene Diät bei refraktärer Epilepsie im Kindesalter. Monatsschr Kinderheilkd 2011; 159: 739-744.
• 18 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314-319.
• 19 Kwan P, Brodie MJ. Effectiveness of first antiepileptic drug. Epilepsia 2001; 42: 1255-1260.
• 20 Kwan P, Arzimanoglou A, Berg AT. et al Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51: 1069-1077.
• 21 Löscher W. Mechanismen von Pharmakoresistenz: Die Bedeutung von Blut-Hirn-Schranke und Multidrug-Transportern. Z Epileptol 2004; 17: 147-148.
• 22 Löscher W, Schmidt D. Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia 2006; 47: 1253-1284.
• 23 Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: Ways out of the current dilemma. Epilepsia 2011; 52: 657-678.
• 24 Mattson RH, Cramer JA, Collins JF. Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group. Neurology 1996; 47: 68-76.
• 25 Neligan A, Bell GS, Sander JW. et al How refractory is refractory epilepsy ? Patterns of relapse and remission in people with refractory epilepsy. Epilepsy Res 2011; 96: 225-230.
• 26 Ohtsuka Y, Yoshinaga H, Kobayashi K. et al Predictors and underlying causes of medically intractable localization-related epilepsy in childhood. Pediatr- Neurol 2001; 24: 209-213.
• 27 Potschka H. Transporterhypothese der Pharmakoresistenz von Epilepsien. Z Epileptol 2010; 23: 152-160.
• 28 Schmidt D, Löscher W. Drug resistance in epilepsy: Putative neurologic and clinical mechanisms. Epilepsia 2005; 46: 858-877.
• 29 Schmidt D. Efficacy of new antiepileptic drugs. Epilepsy Curr 2011; 11: 9-11.
• 30 Semah F, Picot MC, Adam C. et al Is the underlying cause of epilepsy a major prognostic factor for recurrence?. Neurology 1998; 51: 1256-1262.
• 31 Sillanpää M, Jalava M, Kaleva O, Shinnar S. Longterm prognosis of seizures with onset in childhood. N Engl J Med 1998; 338: 1715-1722.
• 32 Sillanpaa M, Schmidt D. Early seizure frequency and aetiology predict long-term medical outcome in childhood-onset epilepsy. Brain 2009; 132: 989-998.
• 33 Sillanpää M, Schmidt D. Is incident drug-resistance of childhood-onset epilepsy reversible? A longterm follow-up study.. Brain 2012 DOI: 10.1093/brain/aws062
• 34 Snead OC. III: Surgical treatment of medically refractory epilepsy in childhood. Brain Dev 2001; 23: 199-207.
• 35 Wiebe S. Outcome measures in intractable epilepsy. AdvNeurol 2006; 97: 11-15.
• 36 Hauser WA. Seizure disorders: the changes with age. Epilepsia 1992; 33 (Suppl. 04) (Suppl) S6-14. Review