Assessment of the reliability, responsiveness, and meaningfulness of the scale for the assessment and rating of ataxia (SARA) for lysosomal storage disorders.

Clinical outcome assessments Lysosomal storage disorders Scale for the assessment and rating of ataxia

Journal

Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161

Informations de publication

Date de publication:
03 Sep 2024
Historique:
received: 19 07 2024
accepted: 23 08 2024
revised: 18 08 2024
medline: 3 9 2024
pubmed: 3 9 2024
entrez: 3 9 2024
Statut: aheadofprint

Résumé

To evaluate the reliability, responsiveness, and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in patients with lysosomal storage disorders (LSDs) who present with neurological symptoms, and quantify the threshold for a clinically meaningful change. We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as re-test reliability between repeat baseline visits or baseline and post-treatment washout visits. Responsiveness was determined in relation to the Investigator's, Caregiver's, and Patient's Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale. The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline and post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e., minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigator's, Caregiver's, and Patient's CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patient's everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia. Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs with CNS involvement, such as NPC and GM2 Gangliosidoses. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

Identifiants

pubmed: 39225743
doi: 10.1007/s00415-024-12664-y
pii: 10.1007/s00415-024-12664-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Julien Park (J)

Department of General Paediatrics, University of Münster, 48149, Münster, Germany. Julien.Park@ukmuenster.de.

Tatiana Bremova-Ertl (T)

Department of Neurology, University Hospital Bern (Inselspital), Bern, Switzerland.

Marion Brands (M)

Department of Paediatric Metabolic Disease, Amsterdam University Medical Center, Amsterdam, Netherlands.

Tomas Foltan (T)

Department of Pediatric Neurology, National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovak Republic.

Matthias Gautschi (M)

Division of Paediatric Endocrinology, Diabetology and Metabolism, Department of Paediatrics, and Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Paul Gissen (P)

NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.

Andreas Hahn (A)

Department of Child Neurology, Justus Liebig University, Giessen, Germany.

Simon Jones (S)

Willink Unit, Manchester Centre for Genomic Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, UK.

Laila Arash-Kaps (L)

SphinCS-Institute of Clinical Science in Lysosomal Storage Disorders, Hochheim, Germany.

Miriam Kolnikova (M)

Department of Pediatric Neurology, National Institute of Children's Diseases, Comenius University in Bratislava, Bratislava, Slovak Republic.

Marc Patterson (M)

Departments of Neurology, Pediatrics and Clinical Genomics, Mayo Clinic Children's Center, Rochester, MN, USA.

Susan Perlman (S)

Department of Neurology, University of California, Los Angeles, CA, USA.

Uma Ramaswami (U)

Lysosomal Storage Disorder Unit, Royal Free London NHS Foundation Trust, London, UK.

Stella Reichmannová (S)

Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Marianne Rohrbach (M)

Division of Metabolism, University Children's Hospital and Children's Research Centre, Zurich, Switzerland.

Susanne A Schneider (SA)

Department of Neurology, Ludwig Maximilians University, Munich, Germany.

Aasef Shaikh (A)

Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Siyamini Sivananthan (S)

NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.

Matthis Synofzik (M)

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.

Mark Walterfarng (M)

Department of Neuropsychiatry, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Pierre Wibawa (P)

Department of Neuropsychiatry, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Kyriakos Martakis (K)

Department of Child Neurology, Justus Liebig University, Giessen, Germany.
Department of Pediatrics, Medical Faculty and University Hospital, University of Cologne, Cologne, Germany.

Mario Manto (M)

Unité Des Ataxies Cérébelleuses, Service de Neurologie, Médiathèque Jean Jacquy, CHU-Charleroi, 6000, Charleroi, Belgium.

Classifications MeSH