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Episodic Vestibular Syndrome with Hyperventilation-Induced Downbeat Nystagmus

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Abstract

Hyperventilation-induced downbeat nystagmus (HV-DBN) has been reported in cerebellar disorders and explained by a loss of the inhibitory cerebellar output via a metabolic effect on cerebellar Ca2+ channels. The aim of this study was to determine the clinical characteristics and underlying pathogenesis of episodic vestibular syndrome (EVS) with HV-DBN. Of 667 patients with EVS, we recruited 22 with HV-DBN and assessed their clinical characteristics, video-oculographic findings, and the results of molecular genetic analyses. The age at symptom onset was 47.5 ± 13.0 years (mean ± SD), and there was a female preponderance (n = 15, 68%). The duration of vertigo/dizziness attacks ranged from minutes to a few days, and 11 patients (50%) fulfilled the diagnostic criteria for vestibular migraine. HV-induced new-onset DBN in 8 patients, while the remaining 14 showed augmentation of spontaneous DBN by HV. The maximum slow-phase velocity of HV-DBN ranged from 2.2 to 11.9°/s, which showed a statistical difference with that of spontaneous DBN (median = 4.95, IQR = 3.68–6.55 vs. median = 1.25, IQR = 0.20–2.15, p < 0.001). HV-DBN was either purely downbeat (n = 11) or accompanied with small horizontal components (n = 11). Other neuro-otologic findings included perverted head-shaking nystagmus (n = 11), central positional nystagmus (n = 7), saccadic pursuit (n = 3), and horizontal gaze-evoked nystagmus (n = 1). Gene expression profiling with a bioinformatics analysis identified 43 upregulated and 49 downregulated differentially expressed genes (DEGs) in patients with EVS and HV-DBN and revealed that the downregulated DEGs were significantly enriched in terms related to the ribosome pathway. Our results suggest that the underlying cerebellar dysfunction would be responsible for paroxysmal attacks of vertigo in patients with EVS and HV-DBN.

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Data Availability

The gene expression data analyzed for this study can be found in the Gene Expression Omnibus under accession number GSE150453: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150453.

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2018R1D1A1A09081786).

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Authors and Affiliations

  1. Department of Neurology, Pusan National University School of Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea

    Eun Hye Oh, **-Hong Shin, Jae Wook Cho & Jae-Hwan Choi

  2. Department of Neurology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea

    Seo Young Choi & Kwang-Dong Choi

  3. School of Systems Biomedical Science, Soongsil University, Seoul, South Korea

    Je-Keun Rhee

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  1. Eun Hye Oh
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Contributions

Dr. Oh acquired and analyzed the data and drafted the manuscript. Drs. Shin, Cho, and S.Y. Choi analyzed and interpreted the data. Dr. K.D. Choi interpreted the data and made a critical revision of the manuscript. Mr. Rhee interpreted the data and conducted statistical analysis. Dr. J.H. Choi conceptualized and designed the study, interpreted the data, and revised the manuscript.

Corresponding author

Correspondence to Jae-Hwan Choi.

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All of the experiments performed in this study followed the tenets of the Declaration of Helsinki. Informed consents were obtained from the participants after the nature and possible consequences of this study had been explained to them. This study was approved by the Institutional Review Board of Pusan National University Yangsan Hospital.

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The authors declare that they have no conflict of interest.

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Oh, E.H., Shin, JH., Cho, J.W. et al. Episodic Vestibular Syndrome with Hyperventilation-Induced Downbeat Nystagmus. Cerebellum 20, 796–803 (2021). https://doi.org/10.1007/s12311-020-01204-9

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