Development of SARA(home), a new video-based tool for the assessment of ataxia at home

BACKGROUND: Clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA) cannot be used to study ataxia at home or to assess daily fluctuations. The objective of the current study was to develop a video-based instrument, SARA(home), for measuring ataxia severity easily and independently at home. METHODS: Based on feasibility of self-application, we selected 5 SARA items (gait, stance, speech, nose-finger test, fast alternating hand movements) for SARA(home) (range, 0-28). We compared SARA(home) items with total SARA scores in 526 patients with spinocerebellar ataxia types 1, 2, 3, and 6 from the EUROSCA natural history study. To prospectively validate the SARA(home), we directly compared the self-applied SARA(home) and the conventional SARA in 50 ataxia patients. To demonstrate feasibility of independent home recordings in a pilot study, 12 ataxia patients were instructed to obtain a video each morning and evening over a period of 14 days. All videos were rated offline by a trained rater. RESULTS: SARA(home) extracted from the EUROSCA baseline data was highly correlated with conventional SARA (r = 0.9854, P < 0.0001). In the prospective validation study, the SARA(home) was highly correlated with the conventional SARA (r = 0.9254, P < 0.0001). Five of 12 participants of the pilot study obtained a complete set of 28 evaluable videos. Seven participants obtained 13-27 videos. The intraindividual differences between the lowest and highest SARA(home) scores ranged from 1 to 5.5. CONCLUSION: The SARA(home) and the conventional SARA are highly correlated. Application at home is feasible. There was a considerable degree of intraindividual variability of the SARA(home) scores

Autosomal Recessive Cerebellar Ataxias in Europe: Frequency, Onset, and Severity in 677 Patients

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.This work was supported by the European Union's Horizon 2020 research and innovation program as part of the innovation project EVIDENCE-RND under the EJP RD COFUND-EJP (825575 to M.S.), as part of Solve-RD (779257 to J.B., M.S., and B.P.v.d.W.), by the DFG under the frame of EJP-RD network PROSPAX (441409627 to M.S. and B.P.v.d.W.), and by the Clinician Scientist program “PRECISE.net” funded by the Else Kröner-Fresenius-Stiftung (to A.T.). The study was further funded by the Federal Ministry of Education and Research, Germany, and through the TreatHSP network (01GM1905 to L.S.). B.P.v.d.W. receives additional research support from ZonMW, NWO, Hersenstichting, Brugling fonds, Gossweiler Foundation, and Radboud university medical center. L.S., T.K., G.Z., B.P.v.d.W., and M.S. are members of the European Reference Network for Rare Neurological Diseases—Project ID 739510. A.T. receives funding from the University of Tübingen, medical faculty, for the Clinician Scientist Program Grant 439-0-0. P.K. receives funding from University of Szeged (Hetényi Géza: 5S330 A202) and Ministry of Innovation and Technology of Hungary, National Research, Development and Innovation Fund (TKP2021-EGA). J.B. was supported by a Senior Clinical Researcher mandate of the Research Fund—Flanders (FWO) under grant agreement number 1805021N and is a member of the μNEURO Research Centre of Excellence of the University of Antwerp. F.M.S. was supported by the Italian Ministry of Health (the EJP-RD network PROSPAX; Ricerca Finalizzata RF-2016-02361610; RF-2019-12370417; Ricerca Corrente, RC 5x1000). Several authors of this publication are members of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD) and of the European Reference Network for Rare Neurological Diseases (ERN-RND). Open Access funding enabled and organized by Projekt DEAL.Peer reviewe

Consensus Recommendations for Clinical Outcome Assessments and Registry Development in Ataxias: Ataxia Global Initiative (AGI) Working Group Expert Guidance

To accelerate and facilitate clinical trials, the Ataxia Global Initiative (AGI) was established as a worldwide research platform for trial readiness in ataxias. One of AGI’s major goals is the harmonization and standardization of outcome assessments. Clinical outcome assessments (COAs) that describe or reflect how a patient feels or functions are indispensable for clinical trials, but similarly important for observational studies and in routine patient care. The AGI working group on COAs has defined a set of data including a graded catalog of COAs that are recommended as a standard for future assessment and sharing of clinical data and joint clinical studies. Two datasets were defined: a mandatory dataset (minimal dataset) that can ideally be obtained during a routine clinical consultation and a more demanding extended dataset that is useful for research purposes. In the future, the currently most widely used clinician-reported outcome measure (ClinRO) in ataxia, the scale for the assessment and rating of ataxia (SARA), should be developed into a generally accepted instrument that can be used in upcoming clinical trials. Furthermore, there is an urgent need (i) to obtain more data on ataxia-specific, patient-reported outcome measures (PROs), (ii) to demonstrate and optimize sensitivity to change of many COAs, and (iii) to establish methods and evidence of anchoring change in COAs in patient meaningfulness, e.g., by determining patient-derived minimally meaningful thresholds of change

SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge

Sexual dysfunction in cervical dystonia and blepharospasm

M Marek,1 M Grobe-Einsler,1 JR Bedarf,1 B Wabbels,2 S Paus1 1Department of Neurology, University of Bonn, Bonn, Germany; 2Department of Ophthalmology, University of Bonn, Bonn, Germany Background: Sexual dysfunction is a frequent, yet underrated, symptom of neurological disease. While knowledge of non-motor comorbidity in focal dystonia is growing rapidly, there is no information on the prevalence of sexual dysfunction in cervical dystonia (CD) or blepharospasm (BL). Methods: In this controlled study, we examined sexual dysfunction in 65 patients with CD and 54 patients with BL by the Arizona Sexual Experience Scale, a validated self-rating scale. Results: Sexual dysfunction was significantly higher in CD patients (45%) than in controls (24%), and frequent in BL (39%). Interestingly, variables of dystonia such as disease duration or severity did not influence sexuality; yet, 23% of CD patients ascribed worsening of their sexual life to dystonia. Symptoms of depression were identified as the most important predictors for sexual dysfunction, followed by age, and personal status (single). Conclusion: Our observations establish sexual dysfunction as a frequent non-motor symptom in CD and BL that is perceived as a burden. It should be considered when investigating patients with adult-onset focal dystonia. Keywords: dystonia, cervical dystonia, blepharospasm, sexual dysfunction, depression&nbsp

SARAspeech—Feasibility of automated assessment of ataxic speech disturbance

Abstract Ataxias are a group of movement disorders that are characterized by progressive loss of balance, impaired coordination and speech disturbance, which together lead to markedly reduced quality of life. Speech disturbance is clinically diagnosed, but methods for objective assessment of severity are lacking. Using 71 sets of speech recordings from ataxia patients, we developed an automated classification system. With a tolerance of ±1 point, this classification system correctly predicted experts’ ratings of speech disturbance according to item 4 of the Scale for Assessment and rating of ataxia (SARA) in 80% of cases. We thereby demonstrate feasibility of computer-assisted voice analysis for automated assessment of severity of speech disturbance

Autosomal Recessive Cerebellar Ataxias in Europe: Frequency, Onset, and Severity in 677 Patients

Progress in next-generation sequencing has led to an explosion of novel genes and phenotypes of autosomal recessive cerebellar ataxias (ARCAs) in the last decade, with >170 recessive conditions manifesting with ataxia identified.1 With large-scale natural history and mechanistic treatment trials on the horizon for many ARCAs, up-to-date knowledge is required not only on relative frequencies but also on real-world age and disease severity distributions as key information for trial design planning and recruitment. In this multicenter study, we provide data on the relative frequency of ARCAs in Europe, delineate the spectrum of age at disease onset, and present real-world data on disease severity distributions of patients with ARCA that help to inform future trial planning