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Amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig disease, causes rapidly progressive muscle atrophy and weakness resulting from the degeneration of both upper and lower motor neurons. ALS causes varying degrees of spasticity, hyperreflexia, and muscle paralysis, eventually leading to pulmonary complications and the need for mechanical ventilatory support. Because there is no cure, clinicians attempt to slow disease progression and preserve function as much as possible. Medical management is directed at preventing pulmonary infections and forestalling terminal respiratory failure.

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Epidemiology

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There are two forms of ALS, the most common of which is sporadic ALS (sALS). The worldwide annual incidence rate for sALS is 0.6 to 2.0 per 100,000, and the prevalence is 4 to 7 per 100,000.1 There are only 1.5 to 2.5 new cases of ALS per 100,000 diagnosed per year.2 In the U.S., 5600 new cases are diagnosed each year, causing an estimated prevalence of 30,000 U.S. ALS patients. The mean age of onset for sALS is 56 years, with a higher incidence in men of up to 1.6:1.0.3 Familial ALS (fALS) is genetically present in only 149 patients from 53 families worldwide (including a rare juvenile form), and there is an endemic focus of ALS in the western Pacific, especially in Guam and the Kii peninsula of Japan. The incidence of fALS is only 10% of that of sALS, with a 1.5-fold higher disease rate for men. Up to 25% of fALS patients have a change in the superoxide dismutase (SOD1) gene, which suggests the ability to test for the disease before symptom onset. There are no racial differences with either of the forms of ALS. There is a higher prevalence of ALS after age 40 years, with prevalence peaking between the ages of 65 and 75. The expected survival rate 48 months after diagnosis is 32%, with a median survival after diagnosis of approximately 30 months.

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Pathophysiology

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The most likely cause of ALS is a genetic SOD1 and/or other genetic mutations causing dysfunction and an abnormal response to a variety of environmental insults. Current theories of cell death in ALS include excitotoxins, such as glutamate, free radicals, heavy metals, viral agents, and autoimmune reactions to tissues such as spinal cord collagen. Programmed cell death as a result of apoptosis is also being studied as a possible etiology of cell death.

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Gross central nervous system (CNS) pathology includes frontal cortical atrophy, degeneration of both the corticospinal and spinocerebellar tracts, a reduction in large cervical and lumbar motor neurons, and cranial nerve nuclei degeneration. Both motor and sensory peripheral nerves undergo axonal degeneration and segmental demyelination, including motor end plate and axon terminal involvement.

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Clinical Features

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Upper motor neuron demyelination and dysfunction causes limb spasticity, hyperreflexia (including Babinski sign and a brisk jaw-jerk reflex), and emotional lability. Associated lower motor neuron dysfunction causes limb ...

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