Neuropediatrics 2015; 46 - PS02-22
DOI: 10.1055/s-0035-1550734

Quinidine: A Targeted Drug Treatment for Patients with the Syndrome of Malignant Migrating Partial Seizures in Infancy and KCNT1 Mutation

T. Dietel 1, M. Wolff 2, S. Leitz 3, M. Viellieber 4, D. Rating 4, G. Kluger 5, T. Bast 1
  • 1Epilepsiezentrum Kork - Klinik für Kinder und Jugendliche, Kehl-Kork, Germany
  • 2Universitätsklinik für Kinder und Jugendliche, Tübingen, Germany
  • 3Klinik für Kinder und Jugendmedizin Klinikum Dritter Orden, München, Germany
  • 4St. Annastiftskrankenhaus, Ludwigshafen, Germany
  • 5Epilepsiezentrum für Kinder und Jugendliche, Schön-Klinik, Vogtareuth, Germany

Aims: Evaluation of effect and side effect von Quinidine in malignant migrating partial seizures in infancy (MMPSI) patients with KCNT mutation

Methods: This study is a retrospective analysis of the three cases.

Results: MMPSI is characterized by electroclinical features of migrating polymorphous focal seizures refractory to antiepileptic treatment and progressive developmental deterioration. The important role of KCNT1 was recently recognized. KCNT1 is expressed in both, cerebral neurons and cardiomyocytes. It plays an important role in the regulation of neuronal excitability. KCNT1 mutations cause a pathogenic gain of function with increased conductance for potassium causing a pathogenic hyperexcitability in vitro. Quinidine acts as a reversible blocker of KCNT1 channels.

We retrospectively report the effect of quinidine in three patients with KCNT1 positive MMPSI. Seizures had started at 91 (range, 1–270 days) days of age and the further course was characterized.

The treatment was started at 14, 24, and 29 months of age, respectively. There was no drop out at the follow-up of 3.7 (range, 3–4 months) months. The maximum doses were 55, 76, and 108 mg/kg/d. All patients had a benefit either because of a decrease of the seizure burden or a reduction of impairing AED without deterioration. The two patients with higher doses showed prolonged QTc time and possibly further symptoms of an overdose with seizure aggravation and/or agitation. Dose reductions to 43 and 46 mg/kg/d lead to a stabilization.

Conclusion: Quinine is effective in patients with MMPSI and KCNT1 mutations as it has been shown in vitro. There was a positive effect on development which, however, was less prominent compared with the one case reported in the literature. The treatment with quinidine is sophisticated because of the narrow therapeutic index, the sensitivity to drug interactions (CYP-450), and possibly life-threatening cardiac side effects.

Keywords: epilepsy, MMPSI, quinidine, potassium channels, genetics, KCNT1.