Amyotrophic lateral sclerosis

A Correction to this article was published on 20 October 2017

Abstract

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and eventual paralysis. Until recently, ALS was classified primarily within the neuromuscular domain, although new imaging and neuropathological data have indicated the involvement of the non-motor neuraxis in disease pathology. In most patients, the mechanisms underlying the development of ALS are poorly understood, although a subset of patients have familial disease and harbour mutations in genes that have various roles in neuronal function. Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria.

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Figure 1: Clinical manifestations of ALS.
Figure 2: Histopathology of ALS.
Figure 3: Pathophysiology of ALS.
Figure 4: Staging systems for ALS.
Figure 5: Factors affecting QOL in patients with ALS.

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Acknowledgements

The images in Figure 2 were prepared with the help of R. Highley (University of Sheffield).

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Contributions

Introduction (O.H.); Epidemiology (G.L.); Mechanisms/pathophysiology (W.R. and P.J.S.); Diagnosis, screening and prevention (O.H. and L.H.v.d.B.); Management (A.C.); Quality of life (Z.S.); Outlook (A.A.-C.); Overview of Primer (E.M.C. and O.H.).

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Correspondence to Orla Hardiman.

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Competing interests

O.H. declares grants from the Health Research Board and Science Foundation Ireland and receives funding through the EU Joint Programme in Neurodegenerative Disease Research (JPND), has served on advisory boards for Biogen Idec, Cytokinetics, Orion, Merck and Roche and has consulted for Mitsubishi. She is Editor-in-Chief of the journal ALS and Frontotemporal Degeneration. A.A.-C. has consulted for Biogen Idec, Chronos Therapeutics, Cytokinetics, GlaxoSmithKline, Mitsubishi Tanabe Pharma and Orion Pharma, has received speaking honoraria from Cytokinetics and Lilly, has been the chief or principal investigator of clinical trials for Biogen Idec, Cytokinetics, GlaxoSmithKline and Orion Pharma and receives royalties for the books The Brain (OneWorld Publications) and Genetics of Complex Human Diseases (Cold Spring Harbor Laboratory Press). A.C. has served on scientific advisory boards for Biogen Idec, Cytokinetics, Italfarmaco, Neuraltus and Mitsubishi. G.L. is an Associate Editor of Neuroepidemiology (Karger Publishers). P.J.S. has served on scientific advisory boards for Biogen, Orion Pharma, Sanofi and Treeway and has received research grants from AstraZeneca, Heptares and Reneuron. Z.S. has received consultation fees from Cytokinetics and Neuralstem and research funding from Biogen, Cytokinetics and GlaxoSmithKline. L.H.v.d.B. declares grants from the ALS Foundation Netherlands, grants from The Netherlands Organization for Health Research and Development (Vici scheme), grants from The Netherlands Organization for Health Research and Development (SOPHIA, STRENGTH, ALS-CarE project), funded through the EU JPND, has served on the Scientific Advisory Boards of Biogen, Cytokinetics and Orion and has received honoraria for presentations from Baxalta. E.M.C. and W.R. declare no competing interests.

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Hardiman, O., Al-Chalabi, A., Chio, A. et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers 3, 17071 (2017). https://doi.org/10.1038/nrdp.2017.71

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