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Clinical diagnosis and management of amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results in progressive loss of bulbar and limb function. Patients typically die from respiratory failure within 3 years of symptom onset. The incidence of ALS in Europe is 2–3 cases per 100,000 individuals in the general population, and the overall lifetime risk of developing the disease is 1:400. ALS is familial in 5% of cases, and shows a Mendelian pattern of inheritance. ALS is recognized to overlap with frontotemporal dementia. Diagnosis is made on clinical grounds, using internationally recognized consensus criteria, after exclusion of conditions that can mimic ALS. The Revised ALS Functional Rating Scale is currently the most widely used assessment tool; scores are used to predict survival, and have been employed extensively in clinical trials. Riluzole remains the only effective drug, and extends the average survival of patients by 3–6 months. Optimal treatment is based on symptom management and preservation of quality of life, provided in a multidisciplinary setting. The discovery of further effective disease-modifying therapies remains a critical need for patients with this devastating condition.

Key Points

  • Amyotrophic lateral sclerosis (ALS) is a syndrome of progressive deterioration involving the corticospinal tract, brainstem, and anterior horn cells of the spinal cord

  • The risk of developing ALS peaks between the ages of 50 years and 75 years; disease rates are elevated in populations of white European ancestry, and reduced in mixed populations

  • No definitive test for ALS exists; the diagnosis is established by excluding other causes of progressive upper motor neuron and lower motor neuron dysfunction

  • Up to 15% of patients with ALS have frontotemporal dementia, and a further 25% have evidence of cognitive impairment, mainly executive dysfunction

  • Clinical care is based on symptom management; however, riluzole, the only available disease-modifying drug, improves patients' survival early in the course of the disease

  • Further improvements in survival will depend on advances in understanding the origins and spread of this syndrome

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Figure 1: Clinical features of ALS.
Figure 2: Voxel-based morphometry image from a patient with ALS.

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Acknowledgements

O. Hardiman was funded by the European Union Health Research 7th Framework Program, 2007–2013, under grant agreement number 259,867, and by the Health Research Board Ireland.

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Correspondence to Orla Hardiman.

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Hardiman, O., van den Berg, L. & Kiernan, M. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol 7, 639–649 (2011). https://doi.org/10.1038/nrneurol.2011.153

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