Long-term evolution of patient-reported outcome measures in spinocerebellar ataxias

Heike Jacobi; Sophie Tezenas du Montcel; Peter Bauer; Paola Giunti; Arron Cook; Robyn Labrum; Michael H Parkinson; Alexandra Durr; Alexis Brice; Perrine Charles; Cecilia Marelli; Caterina Mariotti; Lorenzo Nanetti; Lidia Sarro; Maria Rakowicz; Anna Sulek; Anna Sobanska; Tanja Schmitz-Hübsch; Ludger Schöls; Holger Hengel; Laszlo Baliko; Bela Melegh; Alessandro Filla; Antonella Antenora; Jon Infante; José Berciano; Bart P van de Warrenburg; Dagmar Timmann; Sandra Szymanski; Sylvia Boesch; Wolfgang Nachbauer; Jun-Suk Kang; Massimo Pandolfo; Jörg B Schulz; Audrey Tanguy Melac; Alhassane Diallo; Thomas Klockgether

doi:10.1007/s00415-018-8954-0

Long-term evolution of patient-reported outcome measures in spinocerebellar ataxias

J Neurol. 2018 Sep;265(9):2040-2051. doi: 10.1007/s00415-018-8954-0. Epub 2018 Jun 29.

Authors

Heike Jacobi^{1

2}, Sophie Tezenas du Montcel^{3

4}, Peter Bauer^{5

6}, Paola Giunti⁷, Arron Cook⁷, Robyn Labrum⁸, Michael H Parkinson⁷, Alexandra Durr^{9

10

11

12

13}, Alexis Brice^{9

10

11

12

13}, Perrine Charles¹³, Cecilia Marelli¹⁴, Caterina Mariotti¹⁵, Lorenzo Nanetti¹⁵, Lidia Sarro¹⁵, Maria Rakowicz¹⁶, Anna Sulek¹⁷, Anna Sobanska¹⁶, Tanja Schmitz-Hübsch¹⁸, Ludger Schöls¹⁹, Holger Hengel¹⁹, Laszlo Baliko²⁰, Bela Melegh²¹, Alessandro Filla²², Antonella Antenora²², Jon Infante²³, José Berciano²⁴, Bart P van de Warrenburg²⁵, Dagmar Timmann²⁶, Sandra Szymanski²⁷, Sylvia Boesch²⁸, Wolfgang Nachbauer²⁸, Jun-Suk Kang²⁹, Massimo Pandolfo³⁰, Jörg B Schulz^{31

32}, Audrey Tanguy Melac⁴, Alhassane Diallo³, Thomas Klockgether^{33

34}

Affiliations

¹ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. heike.jacobi@med.uni-heidelberg.de.
² Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. heike.jacobi@med.uni-heidelberg.de.
³ Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, UMRS 1136, INSERM U 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, 75013, Paris, France.
⁴ AP-HP, Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
⁵ Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
⁶ CENTOGENE AG, Rostock, Germany.
⁷ Department of Molecular Neuroscience, UCL, Institute of Neurology, London, UK.
⁸ Neurogenetic Laboratory, National Hospital of Neurology and Neurosurgery, UCL, London, UK.
⁹ INSERM, U 1127, 75013, Paris, France.
¹⁰ CNRS, UMR 7225, 75013, Paris, France.
¹¹ Sorbonne Universités, UPMC Univ Paris 06, UMRS_1127, 75013, Paris, France.
¹² Institut du Cerveau et de la Moelle épinière, ICM, 75013, Paris, France.
¹³ Département de Génétique, APHP, Hôpital de la Pitié-Salpêtrière, 75013, Paris, France.
¹⁴ Service de Neurologie-CMRR, CHRU Gui de Chauliac, 80, av. A. Fliche, 34295, Montpellier Cedex 05, France.
¹⁵ SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
¹⁶ Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland.
¹⁷ Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
¹⁸ Charité Universitätsmedizin Berlin, NeuroCure Clinical Research Center, Berlin, Germany.
¹⁹ Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tübingen and Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), 72076, Tübingen, Germany.
²⁰ Department of Neurology, Zala County Hospital, Zrinyi M. Str. 1, Zalaegerszeg, 8900, Hungary.
²¹ Department of Medical Genetics, Medical School, and Szentagothai Research Center, University of Pécs, Pécs, Hungary.
²² Department of Neuroscience, and Reproductive and Odontostomatological Sciences, Federico II University Naples, Naples, Italy.
²³ Service of Neurology, University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria (UC) and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Santander, Spain.
²⁴ Service of Neurology, University Hospital "Marqués de Valdecilla (IDIVAL)", "Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)", University of Cantabria (UC), Santander, Spain.
²⁵ Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
²⁶ Department of Neurology, University Clinic Essen, University of Duisburg-Essen, Essen, Germany.
²⁷ Department of Neurology, St. Josef Hospital, University Hospital of Bochum, Bochum, Germany.
²⁸ Department of Neurology, Medical University, Innsbruck, Innsbruck, Austria.
²⁹ Department of Neurology, University of Frankfurt, Frankfurt am Main, Germany.
³⁰ Université Libre de Bruxelles (ULB), Neurology Service-ULB Hôpital Erasme, ULB Laboratory of Experimental Neurology, Brussels, Belgium.
³¹ Department of Neurology, RWTH Aachen University, Pauwelsstraβe 30, 52074, Aachen, Germany.
³² JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, 52074, Aachen, Germany.
³³ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
³⁴ Department of Neurology, University Hospital of Bonn, Bonn, Germany.

PMID: 29959555
DOI: 10.1007/s00415-018-8954-0

Abstract

Introduction: To study the long-term evolution of patient-reported outcome measures (PROMs) in the most common spinocerebellar ataxias (SCAs), we analyzed 8 years follow-up data of the EUROSCA Natural History Study, a cohort study of 526 patients with SCA1, SCA2, SCA3 and SCA6.

Methods: To assess the functional capacity in daily living, we used the functional assessment (part IV) of the Unified Huntington's Disease Rating Scale (UHDRS-IV), for health-related quality of life the visual analogue scale of the EuroQol Five Dimensions Questionnaire (EQ-5D VAS), and for depressive symptoms the Patient Health Questionnaire (PHQ-9). Severity of ataxia was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and neurological symptoms other than ataxia with the Inventory of Non-Ataxia Signs (INAS).

Results: UHDRS-IV [SCA1: - 1.35 (0.12); SCA2: - 1.15 (0.11); SCA3: - 1.16 (0.11); SCA6: - 0.99 (0.12)] and EQ-5D [SCA1: - 2.88 (0.72); SCA2: - 1.97 (0.49); SCA3: - 2.06 (0.55); SCA6: - 1.03 (0.57)] decreased linearly, whereas PHQ-9 increased [SCA1: 0.15 (0.04); SCA2: 0.09 (0.03); SCA3: 0.06 (0.04); SCA6: 0.07 (0.04)] during the observational period. Standard response means (SRMs) of UHDRS-IV (0.473-0.707) and EQ-5D VAS (0.053-0.184) were lower than that of SARA (0.404-0.979). In SCA1, higher SARA scores [- 0.0288 (0.01), p = 0.0251], longer repeat expansions [- 0.0622 (0.02), p = 0.0002] and the presence of cognitive impairment at baseline [- 0.5381 (0.25), p = 0.0365] were associated with faster UHDRS-IV decline. In SCA3, higher INAS counts were associated with a faster UHDRS-IV decline [- 0.05 (0.02), p = 0.0212]. In SCA1, PHQ-9 progression was faster in patients with cognitive impairment [0.14 (0.07); p = 0.0396].

Conclusions: In the common SCAs, PROMs give complementary information to the information provided by neurological scales. This underlines the importance of PROMs as additional outcome measures in future interventional trials.

Keywords: ADL; Depression; Natural history studies; Quality of life; Spinocerebellar ataxia; Trinucleotide repeat diseases.

MeSH terms

Activities of Daily Living*
Aged
Depression
Disease Progression
Female
Follow-Up Studies
Humans
Longitudinal Studies
Male
Middle Aged
Patient Reported Outcome Measures
Quality of Life*
Severity of Illness Index
Spinocerebellar Ataxias / physiopathology
Spinocerebellar Ataxias / psychology
Spinocerebellar Ataxias / therapy*

Abstract

MeSH terms

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