The Cerebellum

, Volume 14, Issue 3, pp 284–291 | Cite as

Vestibular Performance During High-Acceleration Stimuli Correlates with Clinical Decline in SCA6

  • Young Eun Huh
  • Ji-Soo KimEmail author
  • Hyo-Jung Kim
  • Seong-Ho Park
  • Beom Seok Jeon
  • Jong-Min Kim
  • Jin Whan Cho
  • David S. Zee
Original Paper


In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33–72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=−0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.


Spinocerebellar ataxia Vertigo Cerebellum Vestibulo-ocular reflex Head impulse test 



This study was supported by a grant of Korea Medical Device Industrial Cooperative Association.

Conflict of Interest

Drs. Huh, Park, J.M. Kim, and J. W. Cho, and Ms. H.J. Kim report no disclosure.

Dr. J.S. Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the Editorial Boards of the Journal of Korean Society of Clinical Neurophysiology, Research in Vestibular Science, Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuro-ophthalmology, and Journal of Vestibular Research and received research support from SK Chemicals, Co. Ltd.

Dr. Jeon has received funding for travel from Novartis Korea and GlaxoSmithKline Korea and has received research support as PI from Norvartis, Boehringer Ingelheim, Ipsen, the Korea Health 21 R&D project, Ministry of Health & Welfare, Republic of Korea (A101273), the National Research Foundation of Korea(NRF), Ministry of Education, Science and Technology (2010-0021653), Advanced Biometric Research Center (ABRC), Korean Science and Engineering Foundation (KOSEF), Seoul National University Hospital, the Mr. Chung Suk-Gyoo and Sinyang Cultural Foundation, and the Song Foundation.

Dr. Zee receives research support from the National Institutes of Health and is an Associate Editor of Frontiers in Neuro-otology and a member of the Editorial Board of the Cerebellum. He received speaker’s honoraria from Abbott and Micromed and from Sun Pharmaceuticals and from the American Academy of Neurology.

Author Contributions

Drs. J.S. Kim and Zee conducted the design and conceptualization of the study, interpretation of the data, and drafting and revising the manuscript. Dr. Huh conducted the design and conceptualization of the study, wrote the manuscript, and analyzed and interpreted the data. Drs. Park, Jeon, J.M. Kim, and Cho contributed to the study concept and design and interpreted the data. Ms. H.J. Kim analyzed and interpreted the data.

Supplementary material

12311_2015_650_MOESM1_ESM.docx (25 kb)
Supplementary Table (DOCX 24 kb)

Video Head impulse test in patient 1. Bedside head impulse tests were positive in both horizontal directions with corrective saccades. Bedside head impulse tests were performed manually with a rapid rotation of the head in the planes of the horizontal canals. Head impulse test was considered abnormal if a corrective saccade had to be generated to maintain fixation on the target because the slow phase was of the wrong amplitude (MPG 975 kb)


  1. 1.
    Gomez CM, Thompson RM, Gammack JT, Perlman SL, Dobyns WB, Truwit CL, et al. Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset. Ann Neurol. 1997;42:933–50.CrossRefPubMedGoogle Scholar
  2. 2.
    Takeichi N, Fukushima K, Sasaki H, Yabe I, Tashiro K, Inuyama Y. Dissociation of smooth pursuit and vestibulo-ocular reflex cancellation in SCA-6. Neurology. 2000;54:860–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Yabe I, Sasaki H, Takeichi N, Takei A, Hamada T, Fukushima K, et al. Positional vertigo and macroscopic downbeat positioning nystagmus in spinocerebellar ataxia type 6 (SCA6). J Neurol. 2003;250:440–3.CrossRefPubMedGoogle Scholar
  4. 4.
    Buttner N, Geschwind D, Jen JC, Perlman S, Pulst SM, Baloh RW. Oculomotor phenotypes in autosomal dominant ataxias. Arch Neurol. 1998;55:1353–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Kim JS, Youn J, Seo DW, Jeong Y, Kang JH, Park JH, et al. Ocular motor characteristics of different subtypes of spinocerebellar ataxia: distinguishing features. Mov Disord. 2013.Google Scholar
  6. 6.
    Zee DS, Yee RD, Cogan DG, Robinson DA, Engel WK. Ocular motor abnormalities in hereditary cerebellar ataxia. Brain. 1976;99:207–34.CrossRefPubMedGoogle Scholar
  7. 7.
    Gordon CR, Joffe V, Vainstein G, Gadoth N. Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease). J Neurol Neurosurg Psychiatry. 2003;74:1403–6.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Yu-Wai-Man P, Gorman G, Bateman DE, Leigh RJ, Chinnery PF. Vertigo and vestibular abnormalities in spinocerebellar ataxia type 6. J Neurol. 2009;256:78–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Crane BT, Tian JR, Demer JL. Initial vestibulo-ocular reflex during transient angular and linear acceleration in human cerebellar dysfunction. Exp Brain Res. 2000;130:486–96.CrossRefPubMedGoogle Scholar
  10. 10.
    Kremmyda O, Kirchner H, Glasauer S, Brandt T, Jahn K, Strupp M. False-positive head-impulse test in cerebellar ataxia. Front Neurol. 2012;3:162.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Park HK, Kim JS, Strupp M, Zee DS. Isolated floccular infarction: impaired vestibular responses to horizontal head impulse. J Neurol. 2013;260:1576–82.CrossRefPubMedGoogle Scholar
  12. 12.
    Ying SH, Choi SI, Lee M, Perlman SL, Baloh RW, Toga AW, et al. Relative atrophy of the flocculus and ocular motor dysfunction in SCA2 and SCA6. Ann N Y Acad Sci. 2005;1039:430–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Rivaud-Pechoux S, Durr A, Gaymard B, Cancel G, Ploner CJ, Agid Y, et al. Eye movement abnormalities correlate with genotype in autosomal dominant cerebellar ataxia type I. Ann Neurol. 1998;43:297–302.CrossRefPubMedGoogle Scholar
  14. 14.
    Velazquez-Perez L, Seifried C, Santos-Falcon N, Abele M, Ziemann U, Almaguer LE, et al. Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2. Ann Neurol. 2004;56:444–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Burk K, Fetter M, Abele M, Laccone F, Brice A, Dichgans J, et al. Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. J Neurol. 1999;246:789–97.CrossRefPubMedGoogle Scholar
  16. 16.
    Hubner J, Sprenger A, Klein C, Hagenah J, Rambold H, Zuhlke C, et al. Eye movement abnormalities in spinocerebellar ataxia type 17 (SCA17). Neurology. 2007;69:1160–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Huh YE, Kim JS. Patterns of spontaneous and head-shaking nystagmus in cerebellar infarction: imaging correlations. Brain. 2011;134:3662–71.CrossRefPubMedGoogle Scholar
  18. 18.
    Saute JA, Donis KC, Serrano-Munuera C, Genis D, Ramirez LT, Mazzetti P, et al. Ataxia rating scales—psychometric profiles, natural history and their application in clinical trials. Cerebellum. 2012;11:488–504.CrossRefPubMedGoogle Scholar
  19. 19.
    Takahashi H, Ishikawa K, Tsutsumi T, Fujigasaki H, Kawata A, Okiyama R, et al. A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6. J Hum Genet. 2004;49:256–64.CrossRefPubMedGoogle Scholar
  20. 20.
    Fahey MC, Cremer PD, Aw ST, Millist L, Todd MJ, White OB, et al. Vestibular, saccadic and fixation abnormalities in genetically confirmed Friedreich ataxia. Brain. 2008;131:1035–45.CrossRefPubMedGoogle Scholar
  21. 21.
    Aw ST, Haslwanter T, Halmagyi GM, Curthoys IS, Yavor RA, Todd MJ. Three-dimensional vector analysis of the human vestibuloocular reflex in response to high-acceleration head rotations. I. Responses in normal subjects. J Neurophysiol. 1996;76:4009–20.PubMedGoogle Scholar
  22. 22.
    Aw ST, Halmagyi GM, Haslwanter T, Curthoys IS, Yavor RA, Todd MJ. Three-dimensional vector analysis of the human vestibuloocular reflex in response to high-acceleration head rotations. II. Responses in subjects with unilateral vestibular loss and selective semicircular canal occlusion. J Neurophysiol. 1996;76:4021–30.PubMedGoogle Scholar
  23. 23.
    Halmagyi GM, Weber KP, Aw ST, Todd MJ, Curthoys IS. Impulsive testing of semicircular canal function. Prog Brain Res. 2008;171:187–94.PubMedGoogle Scholar
  24. 24.
    Cremer PD, Halmagyi GM, Aw ST, Curthoys IS, McGarvie LA, Todd MJ, et al. Semicircular canal plane head impulses detect absent function of individual semicircular canals. Brain. 1998;121(Pt 4):699–716.CrossRefPubMedGoogle Scholar
  25. 25.
    Agrawal Y, Schubert MC, Migliaccio AA, Zee DS, Schneider E, Lehnen N, et al. Evaluation of quantitative head impulse testing using search coils versus video-oculography in older individuals. Otol Neurotol. 2014;35:283–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Lisberger SG, Miles FA, Zee DS. Signals used to compute errors in monkey vestibuloocular reflex: possible role of flocculus. J Neurophysiol. 1984;52:1140–53.PubMedGoogle Scholar
  27. 27.
    Piedras-Renteria ES, Watase K, Harata N, Zhuchenko O, Zoghbi HY, Lee CC, et al. Increased expression of alpha 1A Ca2+ channel currents arising from expanded trinucleotide repeats in spinocerebellar ataxia type 6. J Neurosci. 2001;21:9185–93.PubMedGoogle Scholar
  28. 28.
    Burgess DL, Jones JM, Meisler MH, Noebels JL. Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell. 1997;88:385–92.CrossRefPubMedGoogle Scholar
  29. 29.
    Tully K, Treistman SN. Distinct intracellular calcium profiles following influx through N- versus L-type calcium channels: role of Ca2 + -induced Ca2+ release. J Neurophysiol. 2004;92:135–43.CrossRefPubMedGoogle Scholar
  30. 30.
    Kasumu A, Bezprozvanny I. Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias. Cerebellum. 2012;11:630–9.CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Miyata M, Finch EA, Khiroug L, Hashimoto K, Hayasaka S, Oda SI, et al. Local calcium release in dendritic spines required for long-term synaptic depression. Neuron. 2000;28:233–44.CrossRefPubMedGoogle Scholar
  32. 32.
    Shakkottai VG, Chou CH, Oddo S, Sailer CA, Knaus HG, Gutman GA, et al. Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia. J Clin Invest. 2004;113:582–90.CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Strahlendorf J, Box C, Attridge J, Diertien J, Finckbone V, Henne WM, et al. AMPA-induced dark cell degeneration of cerebellar Purkinje neurons involves activation of caspases and apparent mitochondrial dysfunction. Brain Res. 2003;994:146–59.CrossRefPubMedGoogle Scholar
  34. 34.
    Stahl JS, James RA, Oommen BS, Hoebeek FE, De Zeeuw CI. Eye movements of the murine P/Q calcium channel mutant tottering, and the impact of aging. J Neurophysiol. 2006;95:1588–607.CrossRefPubMedGoogle Scholar
  35. 35.
    De Zeeuw CI, Wylie DR, Stahl JS, Simpson JI. Phase relations of Purkinje cells in the rabbit flocculus during compensatory eye movements. J Neurophysiol. 1995;74:2051–64.PubMedGoogle Scholar
  36. 36.
    Stahl JS, Simpson JI. Dynamics of rabbit vestibular nucleus neurons and the influence of the flocculus. J Neurophysiol. 1995;73:1396–413.PubMedGoogle Scholar
  37. 37.
    Minor LB, Lasker DM, Backous DD, Hullar TE. Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses. J Neurophysiol. 1999;82:1254–70.PubMedGoogle Scholar
  38. 38.
    Chen-Huang C, McCrea RA, Goldberg JM. Contributions of regularly and irregularly discharging vestibular-nerve inputs to the discharge of central vestibular neurons in the alert squirrel monkey. Exp Brain Res. 1997;114:405–22.CrossRefPubMedGoogle Scholar
  39. 39.
    Gierga K, Schelhaas HJ, Brunt ER, Seidel K, Scherzed W, Egensperger R, et al. Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites. Neuropathol Appl Neurobiol. 2009;35:515–27.CrossRefPubMedGoogle Scholar
  40. 40.
    Leigh RJ, Zee DS. The neurology of eye movements. New York: Oxford University Press; 2006.Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Young Eun Huh
    • 1
    • 3
  • Ji-Soo Kim
    • 1
    Email author
  • Hyo-Jung Kim
    • 1
  • Seong-Ho Park
    • 1
  • Beom Seok Jeon
    • 2
  • Jong-Min Kim
    • 1
  • Jin Whan Cho
    • 3
  • David S. Zee
    • 4
  1. 1.Department of Neurology, Seoul National University College of MedicineSeoul National University Bundang HospitalSeongnam-siKorea
  2. 2.Department of Neurology, Seoul National University College of MedicineSeoul National University HospitalSeoulKorea
  3. 3.Department of Neurology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  4. 4.Department of Neurology, Otolaryngology Head and Neck Surgery, Neuroscience, and OphthalmologyThe Johns Hopkins University School of MedicineBaltimoreUSA

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