Amyotrophic lateral sclerosis

The challenges of translational medicine Heterogeneity of sporadic amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) is the most common form of adult motor neuron disease. It is an uncommon but not particularly rare disease with an incidence of 1/100,000 to 3/100,000 individuals (Yoshida et al. 1986) and a male: female ratio of 1.4: 2.5 (Mitsumoto et al. 1998). The prognosis of patients with ALS remains poor, with the mean duration of disease from onset to death approximately 2–5 years. Most patients with ALS die from complications of respiratory failure as a result of diaphragmatic paralysis. Factors suggested as predictors of survival include age at onset, gender, clinical presentation (bulbar vs. spinal), and rate of disease progression. Age at onset appears to be a powerful predictor of disease duration, with younger patients surviving longer. Patients with bulbar onset ALS progress to death more quickly (Eisen et al. 1993a; Haverkamp et al. 1995). In another subset of patients with ALS, a significant percentage (19–39%) survive 5 years and a smaller percentage (8–22%) survive 10 years without ventilator use for respiratory failure. The majority (over 90%) of patients have “sporadic” ALS, that is, ALS without a defined family history of disease. Although it is thought of historically as a neuromuscular disease, current theories based on pathophysiology and natural history suggest that ALS is a neurodegenerative disease. This designation is more appropriate and places ALS in the category of other neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and Huntington's disease. Whereas each of these disorders has a unique clinical presentation and pathological characteristics, one sees significant overlap in pathophysiological and clinical features.