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

被引：1

作者：

Park, Julien ^{[1
]}

Bremova-Ertl, Tatiana ^{[2
]}

Brands, Marion ^{[3
]}

Foltan, Tomas ^{[4
]}

Gautschi, Matthias ^{[5
,6
]}

Gissen, Paul ^{[7
]}

Hahn, Andreas ^{[8
]}

Jones, Simon ^{[9
]}

Arash-Kaps, Laila ^{[10
]}

Kolnikova, Miriam ^{[4
]}

Patterson, Marc ^{[11
]}

Perlman, Susan ^{[12
]}

Ramaswami, Uma ^{[13
]}

Reichmannova, Stella ^{[14
,15
]}

Rohrbach, Marianne ^{[16
,17
]}

Schneider, Susanne A. ^{[18
]}

Shaikh, Aasef ^{[19
]}

Sivananthan, Siyamini ^{[7
]}

Synofzik, Matthis ^{[20
,21
]}

Walterfarng, Mark ^{[22
]}

Wibawa, Pierre ^{[22
]}

Martakis, Kyriakos ^{[8
,23
]}

Manto, Mario ^{[24
]}

机构：

[1] Univ Munster, Dept Gen Paediat, D-48149 Munster, Germany

[2] Univ Hosp Bern, Inselspital, Dept Neurol, Bern, Switzerland

[3] Univ Amsterdam, Med Ctr, Dept Paediat Metab Dis, Amsterdam, Netherlands

[4] Comenius Univ, Natl Inst Childrens Dis, Dept Pediat Neurol, Bratislava, Slovakia

[5] Univ Bern, Bern Univ Hosp, Dept Paediat,Inselspital, Div Paediat Endocrinol Diabetol & Metab, Bern, Switzerland

[6] Univ Bern, Bern Univ Hosp, Inst Clin Chem, Inselspital, Bern, Switzerland

[7] UCL, NIHR Great Ormond St Hosp, Biomed Res Ctr, London, England

[8] Justus Liebig Univ, Dept Child Neurol, Giessen, Germany

[9] Univ Manchester, Royal Manchester Childrens Hosp, Manchester Ctr Genom Med, Willink Unit, Manchester, England

[10] SphinCS, Inst Clin Sci Lysosomal Storage Disorders, Hochheim, Germany

[11] Mayo Clin, Childrens Ctr, Dept Neurol Pediat & Clin Genom, Rochester, MN USA

[12] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA

[13] Royal Free London NHS Fdn Trust, Lysosomal Storage Disorder Unit, London, England

[14] Charles Univ Prague, Fac Med 1, Dept Paediat & Inherited Metab Disorders, Prague, Czech Republic

[15] Gen Univ Hosp, Prague, Czech Republic

[16] Univ Childrens Hosp, Div Metab, Zurich, Switzerland

[17] Childrens Res Ctr, Zurich, Switzerland

[18] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[19] Case Western Reserve Univ, Sch Med, Dept Neurol, Cleveland Hts, OH USA

[20] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany

[21] Univ Tubingen, Ctr Neurol, Tubingen, Germany

[22] Royal Melbourne Hosp, Dept Neuropsychiat, Melbourne, Vic, Australia

[23] Univ Cologne, Univ Hosp, Med Fac, Dept Pediat, Cologne, Germany

[24] CHU Charleroi, Mediatheque Jean Jacquy, Serv Neurol, Unite Ataxies Cerebelleuses, B-6000 Charleroi, Belgium

来源：

JOURNAL OF NEUROLOGY | 2024年

关键词：

Scale for the assessment and rating of ataxia; Lysosomal storage disorders; Clinical outcome assessments; ACETYL-L-LEUCINE; INSTRUMENTS;

D O I：

10.1007/s00415-024-12664-y

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

ObjectiveTo 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.MethodsWe 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.ResultsThe 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.ConclusionQualitative 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.

引用

页码：6888 / 6902

页数：15