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Natural History of Spinocerebellar Ataxia Type 31: a 4-Year Prospective Study

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Abstract

Spinocerebellar ataxia type 31 (SCA31) is known as a late-onset, relatively pure cerebellar form of ataxia, but a longitudinal prospective study on the natural history of SCA31 has not been done yet. In this prospective cohort study, we enrolled 44 patients (mean ± standard deviation 73.6 ± 8.5 years) with genetically confirmed SCA31 from 10 ataxia referral centers in the Nagano area, Japan. Patients were evaluated every year for 4 years using the Scale for the Assessment and Rating of Ataxia (SARA) and the Barthel Index (BI). Of the 176 follow-up visits (91.5%), 161 were completed in this study. Five patients (11.4%) died during the follow-up period, and two patients (4.5%) were lost to follow-up. The annual progression of the SARA score was 0.8 ± 0.1 points/year and that of the BI was −2.3 ± 0.4 points/year (mean ± standard error). Shorter disease duration at baseline was associated with faster progression of the SARA score. Our study indicated the averaged clinical course of SCA31 as follows: the patients develop ataxic symptoms at 58.5 ± 10.3 years, become wheelchair bound at 79.4 ± 1.7 years, and died at 88.5 ± 0.7 years. Our prospective dataset provides important information for clinical trials of forthcoming disease-modifying therapies for cerebellar ataxia. It also represents a useful resource for SCA31 patients and their family members in genetic counseling sessions.

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Acknowledgements

The authors thank Drs. Jun Miki, Kazuma Kaneko, Akiyo Hineno, Daigo Miyazaki, Chinatsu Kobayashi, Ken Takasone, Kazuki Ozawa, Michiaki Kinoshita, and Ryuta Abe for their contribution to the inclusion of the patients in this study. The authors thank Ms. Emi Nomura and Ms. Sonomi Nagasaki for their technical support.

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Authors and Affiliations

  1. Division of Clinical and Molecular Genetics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Katsuya Nakamura

  2. Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Katsuya Nakamura, Kunihiro Yoshida, Akira Matsushima, Mitsuto Sato, Hiroshi Morita & Shu-ichi Ikeda

  3. Division of Neurogenetics, Department of Brain Disease Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Kunihiro Yoshida

  4. Department of Neurology, Kakeyu-Misayama Rehabilitation Center, 1308 Kakeyu-onsen, Ueda, 386-0396, Japan

    Akira Matsushima

  5. Department of Neurology, Ina Central Hospital, 1313-1, Ina, 396-8555, Japan

    Yusaku Shimizu

  6. Department of Neurology, Nagano Red Cross Hospital, Wakasato 5-22-1, Nagano, 380-8582, Japan

    Shunichi Sato & Hiroyuki Yahikozawa

  7. Department of Neurology, Matsumoto Medical Center, Chushin-Matsumoto Hospital, Kotobuki 811, Matsumoto, 390-0021, Japan

    Shinji Ohara

  8. Department of Neurology, Fujimi-kogen Medical Center, Fujimi-kogen Hospital, 11100 Ochiai, Fujimi, 399-0214, Japan

    Masanobu Yazawa

  9. Department of Neurology, Kenwakai Hospital, 1936 Kanaenakadaira, Iida, 395-8522, Japan

    Masao Ushiyama

  10. Department of Neurology, Nagano Prefectural Kiso Hospital, 6613-4, Fukushima, Kiso, 397-8555, Japan

    Atsushi Inoue

Authors
  1. Katsuya Nakamura
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  2. Kunihiro Yoshida
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  4. Yusaku Shimizu
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  6. Hiroyuki Yahikozawa
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  10. Mitsuto Sato
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  11. Hiroshi Morita
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  12. Atsushi Inoue
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  13. Shu-ichi Ikeda
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Corresponding author

Correspondence to Kunihiro Yoshida.

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Source of Funding

This study was supported in part by a grant from the Research Committee for Ataxic Diseases, the Ministry of Health, Labor, and Welfare, Japan (K. Yoshida).

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Figure e-1

Flowchart for the annual follow-up of patients with SCA31. (JPEG 47 kb)

Figure e-2

Correlation between the total SARA score and BI in patients with SCA31 (n = 205 follow-ups). (JPEG 35 kb)

Figure e-3

Required sample size per group in two-group interventional trials of 1-year duration in SCA31 for various effect sizes. (JPEG 36 kb)

Table e-1

Change in the SARA subscores from baseline to Visit 5. (DOCX 16 kb)

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Nakamura, K., Yoshida, K., Matsushima, A. et al. Natural History of Spinocerebellar Ataxia Type 31: a 4-Year Prospective Study. Cerebellum 16, 518–524 (2017). https://doi.org/10.1007/s12311-016-0833-6

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  • DOI: https://doi.org/10.1007/s12311-016-0833-6

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