Objective: To understand health impacts relevant to patients with hereditary spastic paraplegia (HSP) and spastic ataxia (SPAX) by determining the prevalence and relative importance of symptoms in adults and children

Background: HSP and SPAX represent a continuum of rare neurodegenerative disorders along the ataxia-spasticity spectrum. While clinician-reported outcomes, such as the well-established Spastic Paraplegia Rating Scale, assess clinical severity, they do not reflect the perceived disease burden by patients. Understanding the latter, however, is crucial in order to develop treatments with a meaningful change in patients. In this study, we aimed to collect patient-reported information on the presence and impact of medical symptoms through two large-scale self-reported surveys in patients with HSP and SPAX.

Method: Two anonymous, multi-language, multi-national surveys were designed to collect patient-reported symptoms between December 2020 – January 2021 (Survey 1) and January – February 2022 (Survey 2). Survey 1 gathered information on demographics, clinical diagnosis, disease stage and 69 symptoms selected through a literature review and a consensus discussion by the PROSPAX PCOM group. Survey 2 focused on severity and relevance of symptoms, using a refined set of 36 symptom items based on preliminary results from Survey 1.

Results: A total of 616 and 507 individuals across seven language groups (Canadian French, English, Dutch, French, German, Italian, and Turkish) participated in Survey 1 and the follow-up Survey 2, respectively. Genotypic diversity was present across both surveys, with SPG4, SPG7 and ARSACS being the most frequently identified variants. To derive a comprehensive map of functions impacted by HSP we first developed a patient centered ICF core set for HSP grouping the selected question items. Analysis of symptom frequency across reported gender, disease group (HSP vs. SPAX) and defined disease stages (mild, intermediate, advanced) was performed. Mapping of symptom frequency and the respective impact revealed a distinct pattern among disease stages. We further assessed patient-prioritised symptoms for developing treatments in HSP.

Conclusion: This study provides one of the largest datasets regarding patient-reported symptoms in HSP and SPAX. Together with other studies, the information provided will be crucial in order to create meaningful outcomes in clinical trials of rare disease.

References: (1) Synofzik, M., & Schüle, R. (2017). Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways. Movement Disorders, 32(3), 332–345. https://doi.org/10.1002/mds.26944
(2) SchüLe, R., Holland-Letz, T., Klimpe, S., Kassubek, J., Klopstock, T., Mall, V., Otto, S., Winner, B., & SchöLs, L. (2006). The Spastic Paraplegia Rating Scale (SPRS). Neurology, 67(3), 430–434. https://doi.org/10.1212/01.wnl.0000228242.53336.90
(3) Morel, T., & Cano, S. J. (2017). Measuring what matters to rare disease patients – reflections on the work by the IRDiRC taskforce on patient-centered outcome measures. Orphanet Journal of Rare Diseases, 12(1). https://doi.org/10.1186/s13023-017-0718-x
(4) PROSPAX. PROSPAX – an Integrated Multimodal Progression Chart in Spastic Ataxias. https://www.prospax.net. Last accessed on Mar-14-2025

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MDS Abstracts - https://www.mdsabstracts.org/abstract/patient-reported-symptoms-and-their-impact-in-hereditary-spastic-paraplegia-and-spastic-ataxias/