Journal of Neurology

, Volume 255, Issue 5, pp 750–755 | Cite as

Axonal function in a family with episodic ataxia type 2 due to a novel mutation

  • A. V. Krishnan
  • H. Bostock
  • J. Ip
  • M. Hayes
  • S. Watson
  • M. C. KiernanEmail author


Episodic ataxia type 2(EA-2) is a rare, autosomal dominantdisorder characterised by recurrentepisodes of ataxia and dysarthria,due to mutations in the CACNA1A gene on chromosome 19encoding voltage-dependent Ca2+channels. The aim of the presentstudy was to explore whether axonalmembrane properties, assessedusing nerve excitability techniques, were abnormal in patients with EA-2 . Nerve excitability techniqueswere applied to the median nerveof three individuals from threegenerations of a single family, all ofwhom had typical features of EA-2. This family was found to have anovel mutation at codon 1451 ofthe Ca2+ channel alpha 1A subunit.Nerve excitability testing demonstratedsignificant abnormalities,with all patients outside the normal95 % confidence limits in having ahigh rheobase and reduced earlyhyperpolarizing threshold electrotonus. On average there were alsosignificant reductions in refractoriness,late subexcitability and earlydepolarizing threshold electrotonus.Mathematical modelling indicatedthat a similar pattern of abnormalitiesmay result from areduced voltage dependence ofslow K+ channels (KCNQ channels). There are significant and distinctivechanges in peripheralnerve excitability in EA-2 patients,which are presumably induced indirectly. These findings raise thepossibility that excitability testingmay prove a convenient screeningtest for patients with this suspectedchannelopathy.

Key words

episodic ataxia nerve excitability potassiumchannel threshold electrotonus 



episodic ataxia type 2


relative refractory period


threshold electrotonus


depolarizing threshold electrotonus


hyperpolarizing threshold electrotonus


strength-duration time constant


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Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • A. V. Krishnan
    • 1
    • 2
  • H. Bostock
    • 3
  • J. Ip
    • 4
  • M. Hayes
    • 4
  • S. Watson
    • 2
  • M. C. Kiernan
    • 1
    • 2
    Email author
  1. 1.Prince of Wales Medical Research InstituteSydneyAustralia
  2. 2.Institute of Neurological SciencesPrince of Wales HospitalSydneyAustralia
  3. 3.Institute of NeurologyLondonUK
  4. 4.Concord HospitalSydneyAustralia

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