Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 9;272(5):323.
doi: 10.1007/s00415-025-13024-0.

Longitudinal description of health-related quality of life and depressive symptoms in polyQ spinocerebellar ataxia patients

Audrey Iskandar  1 , Maresa Buchholz  2 , Iris Blotenberg  2 , Tanja Schmitz-Hübsch  3 , Jennifer Faber  4   5 , Heike Jacobi  6 , Feng Xie  7 , Marcus Grobe-Einsler  4   5 , Thomas Klockgether  4   5 , Bernhard Michalowsky  2 ; ESMI and EUROSCA Study groups
Collaborators, Affiliations

Longitudinal description of health-related quality of life and depressive symptoms in polyQ spinocerebellar ataxia patients

Audrey Iskandar et al. J Neurol. .

Abstract

Introduction: Due to limited treatment options, managing symptoms has dominated care for Spinocerebellar Ataxia (SCA). Little attention has been given to health-related quality of life (HRQoL) and depressive symptoms experienced by patients across disease duration.

Objective: To investigate the course of HRQoL and the severity of depressive symptoms in SCA from disease onset to 26 years after onset and identify influencing factors.

Methods: We analyzed data from two longitudinal SCA cohorts, the EUROSCA (European Spinocerebellar Ataxia Registry) and ESMI study (European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative). Multilevel mixed-effects models were employed to demonstrate the course of HRQoL and depressive symptoms severity to investigate the role of disease progression with disease duration as a predictor of interest, along with time-varying clinical variables and time-fixed covariates.

Results: Seven hundred seventy four participants (Mage = 50.8 ± 13.4; 48.6% female) were included. HRQoL consistently decreased throughout disease duration across all SCA subtypes, but the decline was smallest in SCA6. The decrease in HRQoL was explained by ataxia and depression severity and driven by increasing problems with self-care, usual activities and mobility. Depressive symptoms significantly increased in SCA2 and 3 only, with a trend toward slight improvement in SCA6.

Conclusions: The trend direction of HRQoL and its significant association with the severity of ataxia symptoms align with the literature. The rapid worsening of self-care problems, the differential associations between depression and HRQoL sub-dimensions in different SCA subtypes, and the unexplainable resilience may warrant a deeper look at patient-specific intra- and interpersonal factors.

Keywords: Ataxia; Genetic disorder; Health-related quality of life; Patient-centered care; Psychologic well-being; Rare disease.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of interest: FX and BM are members of the EuroQol group. The authors declare no competing interests. MB reports no disclosures. NW reports no disclosures. AR reports no disclosures. JF was funded as a fellow of the Cluster for Excellence in Clinical Neuroscience of the Hertie Foundation and received funding of the National Ataxia Foundation (NAF). TS-H receives research grants from Celgene/bms and research grant from Hexal AG. HJ reports no disclosures. FX reports no disclosures. TK is receiving research support from the Bundesministerium für Bildung und Forschung (BMBF), the National Institutes of Health (NIH) and Servier. Within the last 24 months, he has received consulting fees from Biogen, UCB, and Vico Therapeutics. JF was funded within the Advanced Clinician Scientist Programme (ACCENT, funded by the German Federal Ministry of Education and Research (BMBF); funding code 01EO2107) and as a PI of the iBehave Network, sponsored by the Ministry of Culture and Science of the State of North Rhine-Westphalia. JF received funding from the National Ataxia Foundation (NAF) and has received consultancy honoraria from Vico therapeutics, unrelated to the present manuscript. BvdW receives research support from ZonMw, Dutch Scientific Organization, Hersenstichting, and Christina Foundation; has served on scientific advisory boards and/or did paid consultancy for Servier, Biohaven, Vico therapeutics, and Biogen; and receives royalties from BSL/Springer-Nature. AT received research grants from the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und Förderer der Neurologie der Universitätsmedizin Essen”, travel grants from the German Academic Exchange Service (Deutscher Akademischer Austauschdienst, DAAD) and MERCUR/UA (Mercator Research Center Ruhr/ Universitätsallianz Ruhr), and a scholarship of UMEA/ DFG (University Medicine Essen Clinician Scientist Academy—a program funded by the German Research Foundation, Deutsche Forschungsgemeinschaft; FU356/12–1). MMS and LA were funded by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01–0145-FEDER-181240 and through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, under projects 2022.06118.PTDC, UIDB/04539/2020, UIDP/04539/2020 and LA/P/0058/2020, and European funds (GeneT GA 101059981) and by National Ataxia Foundation (NAF). PS was funded by FCT under the grant SFRH/BD/148451/2019. PG is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre UCLH. PG receives also support from the North Thames CRN. PG and HGM, work at University College London Hospitals/ University College London, which receives a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centre’s funding scheme. PG received funding from CureSCA3 in support of HGM work. PG has received grants and honoraria for advisory board from Vico Therapeutics, honoraria for advisory board from Triplet Therapeutics, grants and personal fees from Reata Pharmaceutical, grants from Wave. Ethical approval and consent to participate: ESMI and EUROSCA were approved by the ethics committees of the participating centers and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all study participants.

Figures

Fig. 1
Fig. 1
Participants per disease duration group across all visits
Fig. 2
Fig. 2
Plotted Estimated Marginal Mean of HRQoL (EQ-5D), depressive symptom severity (PHQ-9) and ataxia severity (SARA) over disease duration. Note. SCA subtype was included in the general model to allow for direct comparisons. Age of onset and gender were controlled. Reference lines correspond to the severity cut-off values described in the methods section. EMM (Estimated Marginal Mean) table is available in the Supplementary material
Fig. 3
Fig. 3
Predicted probability of reporting difficulties in each EQ-subdimension following disease onset. Note. The rating 2 & 3 are merged as “problem” and 1 as “no problem”. Only the predicted probability of participants rating “problem” is shown. Self-care shows the fastest rate of change and the largest variability compared to other sub-dimensions. Complete breakdown of each subdimension rating can be observed in Supplementary Fig. 2
See this image and copyright information in PMC

References

    1. Muller U (2021) Spinocerebellar ataxias (SCAs) caused by common mutations. Neurogenetics 22(4):235–250. 10.1007/s10048-021-00662-5 - PMC - PubMed
    1. Bhandari, J., Thada, P.K., and Samanta, D., StatPearls: Spinocerebellar Ataxia. 2024, Treasure Island (FL). - PubMed
    1. Sullivan R, Yau WY, O’Connor E, Houlden H (2019) Spinocerebellar ataxia: an update. J Neurol 266(2):533–544. 10.1007/s00415-018-9076-4 - PMC - PubMed
    1. Paulson HL, Shakkottai VG, Clark HB, Orr HT (2017) Polyglutamine spinocerebellar ataxias—from genes to potential treatments. Nat Rev Neurosci 18(10):613–626. 10.1038/nrn.2017.92 - PMC - PubMed
    1. McIntosh, C.S., Li, D., Wilton, S.D., and Aung-Htut, M.T., Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies. Biomedicines, 2021. 9(11).10.3390/biomedicines9111499. - PMC - PubMed