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Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury
AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a neuromuscular disease that causes degeneration of motor neurons in the cerebral motor cortex, the brainstem, and the spinal cord, which leads to muscle weakness and atrophy. In the final stages of the disease, the muscles responsible for breathing are disrupted; patients often die from respiratory failure. It is estimated that 5–10% of ALS cases are inherited, and the causes of the remaining cases are unknown. ALS affects 20,000–30,000 people in the United States and is more prevalent in men than in women. The risk of the disease increases with age (IOM, 2006).
The committee identified no primary studies and few secondary studies of the relationship between TBI and ALS, but it recognized the importance of evaluating the literature for this outcome because there has been a concern about a relationship of the disease to military service (IOM, 2006).
The committee identified two secondary studies related to ALS. Chen et al. (2007) conducted a case–control study of 110 ALS cases at two major referral centers in New England. The patients, recruited in 1993–1996, received a diagnosis of ALS according to the standard criteria of the World Federation of Neurology and met the following criteria: received the diagnosis within the previous 2 years, lived in New England for half the year, spoke English, and were mentally competent. The control population consisted of 270 people without a diagnosis of dementia, parkinsonism, neuropathy, postpoliomyelitis syndrome, ALS, or other motor neuron diseases. Controls were frequency-matched to cases on age, sex, and telephone area code. Information on subjects and controls was collected by using a structured questionnaire administered by trained interviewers. To determine whether people had TBI, they were asked whether they had ever been injured so severely that they required medical attention and, if so, were then asked for details about the injury to identify TBI. The authors found that a history of TBI was associated with a higher risk of ALS. Compared with those who did not have TBI, there were significantly higher odds of ALS in patients with more than one TBI (OR, 3.1; 95% CI, 1.2–8.1) and in patients who had TBI during the preceding 10 years (OR, 3.2; 95% CI, 1.0–10.2). In patients who had multiple TBIs in the preceding 10 years, the risk of ALS was more than 11 (95% CI, 1.1–114.3), but the number of cases was small.
Kurtzke and Beebe (1980) conducted a case–control study to assess risk factors for ALS. They identified 504 WWII veterans whose deaths were attributed to ALS during 1963–1967. The control population consisted of 504 men matched to subjects on age, entry into military service, and branch of service. To assess the validity of the ALS diagnosis, the authors reviewed hospital records and identified 37 representative deaths attributed to ALS; 36 were found to have definite ALS. The records were also reviewed for information about physical condition on entry into the service and other medical issues, including diseases and injuries. There were eight intracranial injuries in ALS subjects compared with two in controls. The authors found that “men dying of ALS more often had a history of injury 15 or more years before death than did the controls during the same period.”