Amyotrophic lateral sclerosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Amyotrophic Lateral Sclerosis is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. As a motor neuron disease, the disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, develop fasciculations (twitches) because of denervation, and eventually atrophy due to that denervation. The patient may ultimately lose the ability to initiate and control all voluntary movement except of the eyes.
Cognitive function is generally spared except in certain situations such as when ALS is associated with frontotemporal dementia.[1] However, there are reports of more subtle cognitive changes of the frontotemporal type in many patients when detailed neuropsychological testing is employed. Sensory nerves and the autonomic nervous system, which controls functions like sweating, generally remain functional.
Historical Perspective
The word amyotrophic is present Greek in origin. A means no or negative, myo refers to muscle, and trophic means nourishment. When put together it means "no-muscle-nourishment." Lateral identifies the areas of the spinal cord where portions of the nerve cells that signal and control the muscles are located. As this area degenerates it leads to scarring or hardening (sclerosis) in the region. [2]
Classification
ALS is classified into three general groups, familial ALS, sporadic ALS and Guamanian ALS.
Pathophysiology
The cause of ALS is not known. An important step toward answering that question came in 1993 when scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase (SOD1) enzyme were associated with some cases (approximately 20%) of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical. Free radicals are highly reactive molecules produced by cells during normal metabolism. Free radicals can accumulate and cause damage to DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. Current research, however, indicates that motor neuron death is not likely a result of lost or compromised dismutase activity, suggesting mutant SOD1 induces toxicity in some other way (a gain of function).[3][4]
References
- ↑ Phukan J, Pender NP, Hardiman O (2007). "Cognitive impairment in amyotrophic lateral sclerosis". Lancet Neurol. 6 (11): 994–1003. doi:10.1016/S1474-4422(07)70265-X. PMID 17945153.
- ↑ What is ALS - The ALS Association Retrieved October 24, 2006
- ↑ Reaume A, Elliott J, Hoffman E, Kowall N, Ferrante R, Siwek D, Wilcox H, Flood D, Beal M, Brown R, Scott R, Snider W (1996). "Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury". Nat Genet. 13 (1): 43–7. PMID 8673102.
- ↑ Bruijn L, Houseweart M, Kato S, Anderson K, Anderson S, Ohama E, Reaume A, Scott R, Cleveland D (1998). "Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1". Science. 281 (5384): 1851–4. PMID 9743498.