Neurological Sciences

, Volume 36, Issue 8, pp 1393–1396 | Cite as

Exercise-induced downbeat nystagmus in a Korean family with a nonsense mutation in CACNA1A

  • Jae-Hwan Choi
  • Jae-Deuk Seo
  • Yu Ri Choi
  • Min-Ji Kim
  • Jin-Hong Shin
  • Ji Soo Kim
  • Kwang-Dong ChoiEmail author
Original Article


Episodic ataxia type 2 (EA2) is characterized by recurrent attacks of vertigo and ataxia lasting hours triggered by emotional stress or exercise. Although interictal horizontal gaze-evoked nystagmus and rebound nystagmus are commonly observed in patients with EA2, the nystagmus has been rarely reported during the vertigo attack. To better describe exercise-induced nystagmus in EA2, four affected members from three generations of a Korean family with EA2 received full neurological and neuro-otological evaluations. Vertigo was provoked in the proband with running for 10 min to record eye movements during the vertigo attack. We performed a polymerase chain reaction-based direct sequence analysis of all coding regions of CACNA1A in all participants. The four affected members had a history of exertional vertigo, imbalance, childhood epilepsy, headache, and paresthesia. The provocation induced severe vertigo and imbalance lasting several hours, and oculography documented pure downbeat nystagmus during the attack. Genetic analyses identified a nonsense mutation in exon 23 which has been registered in dbSNP as a pathogenic allele (c.3832C>T, p.R1278X) in all the affected members. Ictal downbeat nystagmus in the studied family indicates cerebellar dysfunction during the vertigo attack in EA2. In patients with episodic vertigo and ataxia, the observation of exercise-induced nystagmus would provide a clue for EA2.


Episodic ataxia Exercise Downbeat nystagmus CACNA1A mutation Calcium channel Cerebellar dysfunction 



This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2006640).

Conflict of interest

We have no disclosure of any competing interest.

Supplementary material

10072_2015_2157_MOESM1_ESM.mpg (13.9 mb)
Running for 10 min induced pure downbeat nystagmus in the proband (MPG 14282 kb)


  1. 1.
    Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW, CINCH investigators (2007) Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain 130:2484–2493PubMedCrossRefGoogle Scholar
  2. 2.
    Choi KD, Yook JW, Kim MJ et al (2013) Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2. Neurol Sci 34:1629–1632PubMedCrossRefGoogle Scholar
  3. 3.
    Yue Q, Jen JC, Thwe MM, Nelson SF, Baloh RW (1998) De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia. Am J Med Genet 77:298–301PubMedCrossRefGoogle Scholar
  4. 4.
    Pierrot-Deseilligny C, Milea D (2005) Vertical nystagmus: clinical facts and hypotheses. Brain 128:1237–1246PubMedCrossRefGoogle Scholar
  5. 5.
    Kim HJ, Kim JS, Choi JH, Shin JH, Choi KD, Zee DS (2014) Rebound upbeat nystagmus after lateral gaze in episodic ataxia type 2. Cerebellum 13:411–413PubMedCrossRefGoogle Scholar
  6. 6.
    Kim JM, Kim JS, Ki CS, Jeon BS (2006) Episodic Ataxia Type 2 due to a Deletion Mutation in the CACNA1A Gene in a Korean Family. J Clin Neurol 2:268–271PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Zafeiriou DI, Lehmann-Horn F, Vargiami E, Teflioudi E, Ververi A, Jurkat-Rott K (2009) Episodic ataxia type 2 showing ictal hyperhidrosis with hypothermia and interictal chronic diarrhea due to a novel CACNA1A mutation. Eur J Paediatr Neurol 13:191–193PubMedCrossRefGoogle Scholar
  8. 8.
    Raike RS, Weisz C, Hoebeek FE et al (2013) Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy. Neurobiol Dis 50:151–159PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Fureman BE, Hess EJ (2005) Noradrenergic blockade prevents attacks in a model of episodic dysfunction caused by a channelopathy. Neurobiol Dis 20:227–232PubMedCrossRefGoogle Scholar
  10. 10.
    Timofeeva E, Huang Q, Richard D (2003) Effects of treadmill running on brain activation and the corticotropin-releasing hormone system. Neuroendocrinology 77:388–405PubMedCrossRefGoogle Scholar
  11. 11.
    Jeong YG, Chung SH, Kim CT et al (2006) Corticotropin-releasing factor immunoreactivity increases in the cerebellar climbing fibers in the novel ataxic mutant mouse, pogo. Anat Histol Embryol 35:111–115PubMedCrossRefGoogle Scholar
  12. 12.
    Yue Q, Jen JC, Nelson SF, Baloh RW (1997) Progressive ataxia due to a missense mutation in a calcium-channel gene. Am J Hum Genet 61:1078–1087PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Bain PG, O’Brien MD, Keevil SF, Porter DA (1992) Familial periodic cerebellar ataxia: a problem of cerebellar intracellular pH homeostasis. Ann Neurol 31:147–154PubMedCrossRefGoogle Scholar
  14. 14.
    Walker MF, Zee DS (1999) The effect of hyperventilation on downbeat nystagmus in cerebellar disorders. Neurology 53:1576–1579PubMedCrossRefGoogle Scholar
  15. 15.
    Manto MU (2001) Effects of hyperventilation on fast goal-directed limb movements in spinocerebellar ataxia type 6. Eur J Neurol 8:401–406PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Jae-Hwan Choi
    • 1
  • Jae-Deuk Seo
    • 2
  • Yu Ri Choi
    • 3
  • Min-Ji Kim
    • 3
  • Jin-Hong Shin
    • 1
  • Ji Soo Kim
    • 4
  • Kwang-Dong Choi
    • 3
    Email author
  1. 1.Department of NeurologyPusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan HospitalYangsanKorea
  2. 2.Department of NeurologyBonhospitalBusanKorea
  3. 3.Department of NeurologyCollege of Medicine, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research InstituteBusanKorea
  4. 4.Department of NeurologySeoul National University Bundang HospitalSeongnamKorea

Personalised recommendations