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consecutive non-Quebec ARSACS patients were recruited, and compared to healthy participants from several published and unpublished cohorts.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.
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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.
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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