Evidence of an environmental effect on survival in ALS

Abstract

Amyotrophic lateral sclerosis (ALS, motor neuron disease) is a neurodegenerative disorder of motor neurons leading to paralysis and eventual death by respiratory failure. Median survival is 2–3 years. Susceptibility genes, environmental triggers and disease related prognostic factors have been established, but environmental effects on survival are yet to be investigated. We analysed survival in the South-East England ALS register (SEALS register). Kaplan-Meier and Cox regression analyses were used to investigate survival in London, coastal and rural areas according to postcode at diagnosis. Results showed that there were 933 cases of ALS identified in the catchment area during the study period (1994–January 2012). Cox regression demonstrated a highly significant model for survival with significant protective variables: coastal residency, riluzole use and younger age at onset. Significantly worse survival was associated with London residency, older age as well as definite and probable El Escorial classifications. In conclusion, these findings suggest the possibility of an environmental effect on survival in ALS.

Key words::

• Amyotrophic lateral sclerosis
• motor neuron disease
• population study
• cluster
• survival

Acknowledgements

We thank all the patients with ALS/MND who participated in the SEALS register with the support of their families. We thank the Motor Neurone Disease Association of England, Wales and Northern Ireland, the ALS Association, National Institute for Health Research (NIHR) Dementias and Neurodegenerative Disease Research Network (DeNDRoN), the Angel Fund and the ALS Therapy Alliance for support. This is an EU Joint Programme – Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND - www.jpnd.eu (United Kingdom, Medical Research Council and Economic and Social Research Council). PNL received consultancy fees and expenses from GSK, Biogen-Idec and NeuroNov, for five years. AAC has received consultancy fees from Biogen Idec and Cytokinetics Inc. and royalties from books – The Brain (Oneworld Publications) and Complex Disease Genetics, a Laboratory Manual (Cold Spring Harbor Laboratory Press). Institutional payments include grant income from various charities and governmental organizations.

Declaration of interest: CES and AAC receive salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit and NIHR Biomedical Research Centre 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 to this publication was funded by the European Community's Health Seventh Framework Programme-(FP7/2007–2013; grant agreement number 259867).