A blow to the head trauma–ALS hypothesis
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Hypotheses that amyotrophic lateral sclerosis (ALS) may be caused by antecedent trauma date back to 1911 or earlier.1 They were driven initially by observations that clinical onset of ALS occasionally follows trauma. Their pervasiveness for over a century attests to the needs of patients with ALS, their families, physicians, and researchers to have a tangible etiology for what appears to be an inexplicable fatal disease, preferably an etiology that makes ALS seem less random or gives people some control over it. These hypotheses appeared to be supported at first by epidemiologic studies that subsequently were judged as methodologically flawed. As the quality of studies improved, the appearance of excess association of ALS with antecedent trauma vanished.2 The insight that biological onset of ALS precedes clinical disease by many years has also helped dispel the notion that trauma occurring within months to a few years of clinical onset can cause a disease that is already active.
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