Estimating clinical stage of amyotrophic lateral sclerosis from the ALS Functional Rating Scale

Abstract

ALS is a progressive neurodegenerative disease. The stage of disease reached can be described using a simple system based on the number of central nervous system regions involved. Historically, datasets have not attempted to record clinical stage, but being able to re-analyse the data by stage would have several advantages. We therefore explored the possibility of using an algorithm based on the revised ALS Functional Rating Scale (ALSFRS-R), which is commonly used in clinical practice, to estimate clinical stage. We devised an algorithm to convert ALSFRS-R score into clinical stage. ALSFRS-R domains were mapped to equivalent CNS regions. Stage 4 is reached when gastrostomy or non- invasive ventilation is needed, but as a proxy we used provision. We collected ALSFRS-R from clinic visits, and compared the estimation of clinical stage from the ALSFRS-R with the actual stage. Results showed that the agreement between staging by the two methods was excellent with an intraclass correlation coefficient of 0.92 (95% confidence interval 0.88–0.94). There was no systematic bias towards over-staging or under-staging using the algorithm. In conclusion, we have shown that clinical stage in ALS can be reliably estimated using the ALSFRS-R in historical data and in current data where stage has not been recorded

Key words::

• Epidemiology
• clinical trials
• survival

Acknowledgements

We thank the patients involved in the study.

This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organisations under the aegis of JPND–www.jpnd.eu (United Kingdom, Medical Research Council and Economic and Social Research Council). CES and AAC receive salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The work leading up to this publication was funded by the European Community’s Health Seventh Framework Programme (FP7/2007–2013; grant agreement number 259867). We thank the Motor Neurone Disease Association.

Declaration of interest: RB, AJ, NJ, CK, CME, RaB, CES: no competing interests.

MRT: Consultancy to Biogen Idec.

PNL: Consultancy to GSK and NeuroNova and Grant income from MNDA and DeNDRoN.

AAC: Personal payments: Consultancy to Biogen Idec and Cytokinetics Inc; Royalties from books, The Brain (Oneworld Publications) and Complex Disease Genetics, a Laboratory Manual (Cold Spring Harbor Laboratory Press); Institutional payments: Grant income from various charities and governmental organizations.

The authors alone are responsible for the content and writing of the paper.