Peripheral Nerve Excitability Testing Shows Distinctive Ion Channel Dysfunction in Patients with KCNQ2 Mutations and Epilepsy

  • Dr Susan Tomlinson, University of Sydney, Australia
  • Dr Bronwyn Grinton, University of Melbourne, Australia
  • Prof Hugh Bostock, University College London, United Kingdom
  • Prof Michael Hanna, University College London, United Kingdom
  • Prof Matthew Kiernan, Univeristy of New South Wales, Australia
  • Prof Samuel Berkovic, University of Melbourne, Australia
  • Prof David Burke, University of Sydney, Australia
  • Prof Ingrid Scheffer, University of Melbourne, Australia

Background: Neuronal ion channel disorders can manifest as epilepsy, migraine, ataxia and neuromyotonia. Clinical diagnosis is challenging as features may be paroxysmal. Structural assessment is unhelpful because channelopathies predominantly affect neuronal function. Nerve excitability studies provide multidimensional information about the function of ion channels expressed in peripheral axons. The aim of this study was to test the hypothesis that the genetic channelopathy Benign Familial Neonatal Convulsions (BFNC)due to mutations of KCNQ2 encoding the Kv7.2 subunit of slow axonal potassium channels is associated with characteristically abnormal peripheral nerve excitability, even in the absence of peripheral nerve signs.
Methods: Eight patients from 3 families with KCNQ2 mutations underwent nerve excitability testing. Seven had been seizure-free for many years. Results were compared to 16 age-matched controls.
Results: Each family had different KCNQ2 mutations: 2 deletions and one missense mutation. No patient had clinical evidence of neuromyotonia. Excitability studies revealed an 18% reduction in accommodation to depolarising conditioning stimuli during threshold electrotonus (p=0.0001) and a 36% decrease in late subexcitability during the recovery cycle (p=0.0001).
Conclusions: Nerve excitability testing in BFNC patients shows distinctive abnormalities, appropriate for a reduction in slow potassium current. Peripheral nerve excitability studies may have a clinical role to aid diagnosis of neuronal ion channel disorders, even when only the central nervous system appears clinically affected.