Journal article

Quinidine in the Treatment of KCNT1-Positive Epilepsies

Mohamad A Mikati, Yong-hui Jiang, Michael Carboni, Vandana Shashi, Slave Petrovski, Rebecca Spillmann, Carol J Milligan, Melody Li, Annette Grefe, Allyn McConkie, Samuel Berkovic, Ingrid Scheffer, Saul Mullen, Melanie Bonner, Steven Petrou, David Goldstein

ANNALS OF NEUROLOGY | WILEY | Published : 2015


We report 2 patients with drug-resistant epilepsy caused by KCNT1 mutations who were treated with quinidine. Both mutations manifested gain of function in vitro, showing increased current that was reduced by quinidine. One, who had epilepsy of infancy with migrating focal seizures, had 80% reduction in seizure frequency as recorded in seizure diaries, and partially validated by objective seizure evaluation on EEG. The other, who had a novel phenotype, with severe nocturnal focal and secondary generalized seizures starting in early childhood with developmental regression, did not improve. Although quinidine represents an encouraging opportunity for therapeutic benefits, our experience suggest..

View full abstract



Funding Acknowledgements

This study was supported by grants from the National Health and Medical Research Council (S.B., I.S., S.M.), NIH National Institute of Neurological Disorders and Stroke (S.B.), and NIH Centers without Walls "Epi4K" (I.S.), and an early career fellowship from the National Health and Medical Research Council (S.M.).