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Coordination and timing deficits in speech and swallowing in autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS)

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Abstract

Background

Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a rare early onset neurodegenerative disease that typically results in ataxia, upper motor neuron dysfunction and sensorimotor peripheral neuropathy. Dysarthria and dysphagia are anecdotally described as key features of ARSACS but the nature, severity and impact of these deficits in ARSACS are not known. A comprehensive quantitative and qualitative characterization of speech and swallowing function will support diagnostics, provide insights into the underlying pathology, and guide day-to-day clinical management.

Methods

11 consecutive non-Quebec ARSACS patients were recruited, and compared to healthy participants from several published and unpublished cohorts. A comprehensive behavioural assessment including objective acoustic analysis and expert perceptual ratings of motor speech, the Clinical Assessment of Dysphagia in Neurodegeneration (CADN), videofluoroscopy and standardized tests of dysarthria and swallowing related quality of life was conducted.

Results

Speech in this ARSACS cohort is characterized by pitch breaks, prosodic deficits including reduced rate and prolonged intervals, and articulatory deficits. The swallowing profile was characterized by delayed initiation of the swallowing reflex and late epiglottic closure. Four out of ten patients were observed aspirating thin liquids on videofluoroscopy. Patients report that they regularly cough or choke on thin liquids and solids during mealtimes. Swallowing and speech-related quality of life was worse than healthy controls on all domains except sleep.

Conclusions

The dysphagia and dysarthria profile of this ARSACS cohort reflects impaired coordination and timing. Dysphagia contributes to a significant impairment in functional quality of life in ARSACS, and appears to manifest distinctly from other ARSACS dysfunctions such as ataxia or spasticity.

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Acknowledgements

This study was supported by the Ataxia Charlevoix–Saguenay Foundation and from the European Union’s Horizon 2020 research and innovation program under the ERA-NET Cofund action N° 643578. It was supported by the BMBF (01GM1607 to M. S.), under the frame of the E-Rare-3 network PREPARE (to M. S. and C. G.). A. P. V. receives salaried support from the National Health and Medical Research Council, Australia (Career Development Fellowship ID 1082910), received funding from the Alexander von Humboldt Foundation.

Funding

A/Prof Vogel is chief science officer of Redenlab who aided the acoustic analysis. He also receives institutional support from The University of Melbourne. Ms. Rommel, Ms. Stoll, Ms. Kraus, Mr. Oettinger, Dr. Gagnon, Prof. Horger, Dr. Krumm all have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

    Adam P. Vogel, Natalie Rommel, Lisa H. Stoll, Eva-Maria Kraus, Ludger Schöls & Matthis Synofzik

  2. Center for Neurology, University Hospital Tübingen, Tübingen, Germany

    Adam P. Vogel, Natalie Rommel, Lisa H. Stoll, Eva-Maria Kraus, Ludger Schöls & Matthis Synofzik

  3. Centre for Neuroscience of Speech, The University of Melbourne, 550 Swanston Street, Parkville, Melbourne, VIC, 3010, Australia

    Adam P. Vogel

  4. Redenlab, Melbourne, Australia

    Adam P. Vogel

  5. Therapiezentrum, University Hospital Tübingen, Tübingen, Germany

    Natalie Rommel & Lisa H. Stoll

  6. Neurology and Rehabilitation, Kliniken Schmieder, Gailingen am Hochrhein, Germany

    Andreas Oettinger

  7. Groupe de recherche interdisciplinaire sur les maladies neuromusculaires (GRIMN), Jonquière, QC, Canada

    Cynthia Gagnon

  8. Clinique des maladies neuromusculaires, Centre de réadaptation en déficience physique Le Parcours du Centre de santé et de services sociaux de Jonquière, Jonquière, QC, Canada

    Cynthia Gagnon

  9. Centre hospitalier affilié universitaire régional (CAUR) de Chicoutimi, Centre de santé et de services sociaux de Chicoutimi, Chicoutimi, QC, Canada

    Cynthia Gagnon

  10. Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany

    Marius Horger & Patrick Krumm

  11. Department of Neurology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany

    Dagmar Timmann

  12. Department of Medicine, Monash University, Melbourne, Australia

    Elsdon Storey

  13. Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany

    Ludger Schöls & Matthis Synofzik

Authors
  1. Adam P. Vogel
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  2. Natalie Rommel
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  6. Cynthia Gagnon
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  7. Marius Horger
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  8. Patrick Krumm
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  9. Dagmar Timmann
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  10. Elsdon Storey
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  11. Ludger Schöls
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Contributions

Prof. APV contributed to the design of the study, collection, analysis and interpretation of the data, and drafting the manuscript. He also supervised students, led the research team, and obtained funding for the research. Ms. NR contributed to the design of the study, collected data, analysis and interpretation of the data, revising the manuscript for intellectual content, and supervision of students. Mr. AO contributed to data analysis and interpretation, and revising the manuscript for intellectual content. Ms. LHS contributed to data analysis and interpretation, and revising the manuscript for intellectual content. Ms. EK contributed to data analysis and interpretation, and revising the manuscript for intellectual content. Dr. CG contributed to data analysis and interpretation, and revising the manuscript for intellectual content. Prof. MH and Dr. PK contributed to administering and interpreting the VFSS and revising the manuscript for intellectual content. Prof. DT contributed to patient recruitment and examination, data interpretation and revising the manuscript for intellectual content. Prof. Dr. LS and Prof. ES contributed to data interpretation and revising the manuscript for intellectual content. Dr. MS contributed to the design of the study, collection, analysis and interpretation of the data, and revising the manuscript for intellectual content. He also supervised students, led the research team, and obtained funding for the research.

Corresponding author

Correspondence to Adam P. Vogel.

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Conflicts of interest

Prof. Timmann receives funding from the German Research Foundation (DFG), the Mercator Research Center Ruhr and the German Heredoataxia Foundation unrelated to this study. Prof. Storey receives funding from the NIH, unrelated to this study. Prof. Dr. Schöls receives funding from the German Research Foundation (DFG), the European Union and the German Hereditary Spastic Paraplegia Foundation unrelated to this study. Dr. Synofzik received honoraria from Actelion pharmaceuticals, unrelated to the current study.

Ethical standards

The study received institutional approval from the Medical Ethics Board, University Hospital Tübingen, Germany (Az. 003/2015BO2) and The University of Melbourne Human Research Ethics Committee. All patients, or representatives, provided written informed consent. The project was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Vogel, A.P., Rommel, N., Oettinger, A. et al. Coordination and timing deficits in speech and swallowing in autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS). J Neurol 265, 2060–2070 (2018). https://doi.org/10.1007/s00415-018-8950-4

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  • DOI: https://doi.org/10.1007/s00415-018-8950-4

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