Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a rare and fatal neurodegenerative disorder affecting both upper motor neurons, found in the motor cortex of the brain, and lower motor neurons, found in the brain stem and spinal cord. Though first described in 1874 by Jean Martin Charcot, a French physician, there was not much interest in ALS until the mid-1900s, when a cluster of cases was found on Guam. (1)

This motor neuron disorder is thought to have both genetic and environmental risk factors, with exposure to BMAA and BMAA-like molecules, neurotoxins produced by cyanobacteria and diatoms and found in cycad seeds, being a particularly important environmental risk factor. ALS due primarily to environmental factors is termed “sporadic ALS,” and is responsible for the vast majority of cases (2). Hereditary ALS, which may be caused by both dominant and recessive genetic mutations and is deemed “familial ALS,” accounts for 5-10% of ALS cases (1,2). Familial ALS has an average onset of between 47-52 years, and onset approximately 10 years earlier than sporadic ALS, which most commonly appears in individuals 58-63 years of age, and unlike sporadic ALS, does not differ in incidence between the sexes (2).

ALS has been found to have the greatest incidence in individuals in their 60s, with the lowest incidences in individuals under 40 years and individuals over 80 years of age (4). Worldwide, the average incidence of ALS is fairly uniform at 1.5-2.5 per 100,000 persons per year (3). Within the United States, as of 2012, there was found to be a prevalence of 3.9 cases per 100,000 individuals, with the highest prevalence amongst individuals in their 70s, meaning that 10,000-25,000 Americans currently suffer from ALS (4,5). The risk of developing ALS has been found to vary by demographic: being white, being of high socioeconomic class, and being male have been found to correlate with a greater likeliness of developing ALS (6), with males having an incidence of 3.0 per 100,000 individuals, 125% the incidence in females, 2.4 per 100,000 (2).

Signs of both upper motor neuron and lower motor neuron degeneration, as well as evidence of effects in multiple regions of the body, must to be present for ALS diagnosis, as no definitive laboratory test exist to detect ALS (1). Damage to the upper motor neurons results in stiff limbs, spastic limb movement, and exaggerated reflex responses, while damage to the lower motor neurons results in muscle atrophy, particularly in muscles of the face, limbs, and respiratory system, which leads to difficulty speaking, swallowing, and breathing, and the disappearance of the reflex response (1). Symptoms may begin with either upper or lower motor neuron degeneration, and this, along with the varying rates of onset and diversity in progression, make diagnoses difficult (1,5).

Once symptoms have begun to develop, a patient’s life expectancy averages around 2-5 years, though 10-20% of patients with ALS may survive for over 10 years, with younger patients having, on average, a longer life expectancy (3,4), and mortality resulting from the failure of the muscles of the respiratory system (5). The drug riluzole, which is thought to effect metabolism of the neurotransmitter glutamate, has been found to improve life expectancy by 2 months, though how exactly it effects these results is still relatively unknown (3). Researchers continue to search for cures and more effective treatments for ALS.

References:

1. MD, H. M. (2009). Amyotrophic Lateral Sclerosis: A Guide for Patients and Families, Third Edition. Demos Medical Publishing.
2. Kiernan, M. C., Vucic, S., Cheah, B. C., Turner, M. R., Eisen, A., Hardiman, O., … Zoing, M. C. (2011). Amyotrophic lateral sclerosis. The Lancet, 377(9769), 942–955. http://doi.org/10.1016/S0140-6736(10)61156-7
3. Beghi, E., Chiò, A., Couratier, P., Esteban, J., Hardiman, O., Logroscino, G., … (*) O. B. O. T. E. C. (2011). The epidemiology and treatment of ALS: Focus on the heterogeneity of the disease and critical appraisal of therapeutic trials. Amyotrophic Lateral Sclerosis, 12(1), 1–10. http://doi.org/10.3109/17482968.2010.502940
4. Prevalence of Amyotrophic Lateral Sclerosis — United States, 2010–2011. (n.d.). Retrieved December 8, 2015, from http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6307a1.htm
5. Amy Chen, J. M. (2008). The Role of Exercise in Amyotrophic Lateral Sclerosis. Physical Medicine and Rehabilitation Clinics of North America, 19(3), 545–57, ix–x. http://doi.org/10.1016/j.pmr.2008.02.003
6. Henry, K. A., Fagliano, J., Jordan, H. M., Rechtman, L., & Kaye, W. E. (2015). Geographic Variation of Amyotrophic Lateral Sclerosis Incidence in New Jersey, 2009–2011. American Journal of Epidemiology, 182(6), 512–519. http://doi.org/10.1093/aje/kwv095