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Epidemiology and pathogenesis of amyotrophic lateral sclerosis

Nicholas J Maragakis, MD
Nestor Galvez-Jimenez, MD, MSc, MHSA, FACP
Section Editors
Jeremy M Shefner, MD, PhD
Ira N Targoff, MD
Deputy Editor
John F Dashe, MD, PhD


Amyotrophic lateral sclerosis (ALS), first described by Charcot in the nineteenth century [1], is a relentlessly progressive neurodegenerative disorder that causes muscle weakness, disability, and eventually death, with a median survival of three to five years. ALS is also known by the eponym "Lou Gehrig's Disease," after the famous baseball player who was affected with the disorder. Motor neuron disease (MND) is the preferred term in the United Kingdom, but in the United States ALS and MND are sometimes used interchangeably.

Historically, ALS was identified as a clinical syndrome distinguishable from other motor neuron diseases such as primary lateral sclerosis, primary muscular atrophy, and progressive bulbar palsy, based upon the location of first symptom and the extent to which anterior horn cells or corticomotor neurons are initially involved. However, it is increasingly evident that ALS is clinically and pathophysiologically diverse [2], with clear overlap with frontotemporal dementia [3]. Multiple genetic mutations may lead to a similar clinical phenotype, while a single mutation may be associated with pure ALS, ALS with frontotemporal dementia, or pure frontotemporal dementia. These conditions exist on a clinicopathologic spectrum, with potentially different etiologies that share a final common pathway leading to upper and lower motor neuron degeneration. It is therefore appropriate to place ALS among the neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, and Huntington disease.

The epidemiology and pathogenesis of ALS are discussed in this topic review. Other aspects of ALS are discussed separately. (See "Familial amyotrophic lateral sclerosis" and "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease" and "Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease".)


Amyotrophic lateral sclerosis (ALS) is classified as either sporadic or familial:

Sporadic forms account for 90 to 95 percent of ALS cases.

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