Editors' ChoiceEpilepsy

Sudden Death in Epilepsy: A Shot to the Heart?

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Science Translational Medicine  05 May 2010:
Vol. 2, Issue 30, pp. 30ec72
DOI: 10.1126/scitranslmed.3001226

Why are some individuals with epilepsy at high risk of sudden death? Lethal cardiac arrhythmias may play a role, but the link between brain and heart in this disorder has remained elusive. A breakthrough was suggested, however, with the recent discovery by Noebels and colleagues that mice bearing a human disease–linked mutation in the gene coding for potassium channel subtype Kv1.1 exhibit spontaneous seizures that lead to fatal cardiac arrhythmias. New research published by this group has now shed light on how this might occur. They deleted Kcna1, the gene encoding for the Kv1.1 potassium channel, in a strain of mice and then monitored their hearts and brains with simultaneous electrical recordings (electrocardiograms and electroencephalograms). Although the structure of the heart was apparently not altered in these mice, their hearts exhibited electrical defects, even between seizures: atrioventricular conduction blocks, bradycardia, and premature ventricular contractions. During seizures, the frequency of atrioventricular conduction blocks increased further, predisposing the animals to sudden death. Pharmacological blockade of parasympathetic outflow with atropine ameliorated the conduction blocks, whereas sympathetic blockade alone with propranolol was without effect. Further, wild-type mice expressed Kv1.1 extensively in specialized regions of the vagus nerve, which is the major source of parasympathetic innervation of the heart. This evidence suggests that deficient Kv1.1 action leads to impaired neural control of cardiac rhythmicity through altered parasympathetic neurotransmission. Accordingly, Kcna1 is a strong candidate gene for sudden unexplained death in epilepsy. The mystery of sudden death in this illness may finally emerge from the darkness.

E. Glasscock et al., Kv1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction as a candidate mechanism for sudden unexplained death in epilepsy. J. Neurosci. 30, 5167–5175 (2010). [Abstract]

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