Alhassane Diallo1, Heike Jacobi2,3, Tanja Schmitz-Hübsch4, Arron Cook5, Robyn Labrum6, Alexandra Durr7,8,9, Alexis Brice7,8,9, Perrine Charles10, Cecilia Marelli11, Caterina Mariotti12, Lorenzo Nanetti12, Marta Panzeri12, Maria Rakowicz13, Anna Sobanska13, Anna Sulek14, Ludger Schöls15, Holger Hengel15, Bela Melegh16, Alessandro Filla17, Antonella Antenora17, Jon Infante18, José Berciano18, Bart P van de Warrenburg19, Dagmar Timmann20, Sylvia Boesch21, Massimo Pandolfo22, Jörg B Schulz23,24, Peter Bauer25, Paola Giunti5, Laszlo Baliko26, Michael H Parkinson5, Jun-Suk Kang27, Thomas Klockgether28, Sophie Tezenas du Montcel1,29. 1. Paris-Sorbonne Universités Université Pierre et Marie Curie UMR 1136 Institut National de la Santé et de la Recherche Médicale (INSERM) Institut Pierre Louis d'Epidémiologie et de Santé Publique Paris France. 2. Department of Neurology University Hospital of Bonn Bonn Germany. 3. Department of Neurology University Hospital of Heidelberg Heidelberg Germany. 4. Clinical Neuroimmunology Groupe NeuroCure Clinical Research Center Charité Universitätsmedizin Berlin Berlin Germany. 5. Department of Molecular Neuroscience Institute of Neurology University College London London United Kingdom. 6. Neurogenetic Laboratory National Hospital of Neurology and Neurosurgery University College London Hospitals London United Kingdom. 7. Paris-Sorbonne Universités Université Pierre et Marie Curie UMR S1127 INSERM Paris France. 8. Centre National de la Recherche Scientifique Institut du Cerveau et de la Moelle Épinière UMR 7225 Assistance Publique-Hôpitaux de Paris Paris France. 9. Genetic Department Pitié-Salpêtrière University Hospital Paris France. 10. Genetic Department Pitié-Salpêtrière University Hospital Assistance Publique-Hôpitaux de Paris Paris France. 11. Service de Neurologie Centre Mémoire de Resources et de Recherche Hôpital Gui de Chauliac Montpellier France. 12. SOSD Genetics of Neurodegenerative and Metabolic Diseases Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Milan Italy. 13. Department of Clinical Neurophysiology Institute of Psychiatry and Neurology Warsaw Poland. 14. Department of Genetics Institute of Psychiatry and Neurology Warsaw Poland. 15. Department of Neurodegeneration and Hertie Institute for Clinical Brain Research University of Tübingen and Deutsches Zentrum für Neurodegenerative Erkrankungen Tübingen Germany. 16. Department of Medical Genetics and Szentagothai Research Center University of Pécs Pécs Hungary. 17. Department of Neuroscience and Reproductive and Odontostomatological Sciences Federico II University Naples Italy. 18. Neurology Service University Hospital Marqués de Valdecilla University of Cantabria and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) Santander Spain. 19. Department of Neurology Donders Institute for Brain, Cognition and Behavior Radboud University Medical Center Nijmegen the Netherlands. 20. Department of Neurology University Clinic Essen University of Duisburg-Essen Duisburg Germany. 21. Department of Neurology Medical University Innsbruck Innsbruck Austria. 22. Neurology Service Laboratory of Experimental Neurology Université Libre de Bruxelles Hôpital Erasme Brussels Belgium. 23. Department of Neurology Rheinisch-Westfälische Technische Hochschule Aachen University Aachen Germany. 24. Jülich Aachen Research Alliance-Translational Brain Medicine Aachen Germany. 25. Institute of Medical Genetics and Applied Genomics University of Tübingen Tübingen Germany. 26. Department of Neurology Zala County Hospital Zalaegerszeg Hungary. 27. Department of Neurology University of Frankfurt Frankfurt am Main Germany. 28. Department of Neurology and German Center for Neurodegenerative Diseases University Hospital of Bonn Bonn Germany. 29. Biostatistics Unit Groupe Hospitalier Pitié-Salpêtrière AP-HP Paris France.
Abstract
BACKGROUND: Spinocerebellar ataxias (SCAs) are dominantly inherited, progressive ataxia disorders. Disease progression could be preceded by weight loss. OBJECTIVES: We aimed to study the course of weight loss in patients who had the most common SCAs (SCA1, SCA2 SCA3, and SCA6). Additional objectives were to identify subgroups of weight evolution, to determine the factors influencing these evolutions, and to assess the impact of these evolutions on disease progression. METHODS: In total, 384 patients from the EUROSCA prospective cohort study were analyzed who had SCA1, SCA2, SCA3, or SCA6 and at least 3 measurements of weight. Age was used as a time scale. Clinical outcomes were body mass index (BMI) and the Scale for the Assessment and Rating Ataxia (SARA), with scores ranging from 0 to 40. We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup BMI evolution. RESULTS: Overall, BMI declined over time (-0.11 ± 0.03 kg/m2 per decade; P = 0.0009). Three subgroups of BMI evolution were identified: "decreasing BMI" (n = 88; 23%), "increasing BMI" (n = 70; 18%) and "stable BMI" (n = 226; 59%). Patients in the decreasing BMI group were more severely affected at baseline with higher SARA scores and a higher frequency of non-ataxia signs (especially motor symptoms) compared with those in the other groups. Weight loss was associated with faster disease progression (5.7 ± 0.7 SARA points per decade; P = 0.036). CONCLUSIONS: The current data have substantial implications for the design of future interventional studies in SCA, as they provide a basis for patient stratification and emphasize the usefulness of BMI as a biomarker for monitoring disease progression.
BACKGROUND: Spinocerebellar ataxias (SCAs) are dominantly inherited, progressive ataxia disorders. Disease progression could be preceded by weight loss. OBJECTIVES: We aimed to study the course of weight loss in patients who had the most common SCAs (SCA1, SCA2 SCA3, and SCA6). Additional objectives were to identify subgroups of weight evolution, to determine the factors influencing these evolutions, and to assess the impact of these evolutions on disease progression. METHODS: In total, 384 patients from the EUROSCA prospective cohort study were analyzed who had SCA1, SCA2, SCA3, or SCA6 and at least 3 measurements of weight. Age was used as a time scale. Clinical outcomes were body mass index (BMI) and the Scale for the Assessment and Rating Ataxia (SARA), with scores ranging from 0 to 40. We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup BMI evolution. RESULTS: Overall, BMI declined over time (-0.11 ± 0.03 kg/m2 per decade; P = 0.0009). Three subgroups of BMI evolution were identified: "decreasing BMI" (n = 88; 23%), "increasing BMI" (n = 70; 18%) and "stable BMI" (n = 226; 59%). Patients in the decreasing BMI group were more severely affected at baseline with higher SARA scores and a higher frequency of non-ataxia signs (especially motor symptoms) compared with those in the other groups. Weight loss was associated with faster disease progression (5.7 ± 0.7 SARA points per decade; P = 0.036). CONCLUSIONS: The current data have substantial implications for the design of future interventional studies in SCA, as they provide a basis for patient stratification and emphasize the usefulness of BMI as a biomarker for monitoring disease progression.
Entities:
Keywords:
body mass index; latent class mixed model; longitudinal data; spinocerebellar ataxia
Authors: 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; Marta Panzeri; 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; Jun-Suk Kang; Massimo Pandolfo; Jörg B Schulz; Sonia Molho; Alhassane Diallo; Thomas Klockgether Journal: Lancet Neurol Date: 2015-09-13 Impact factor: 44.182
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