DISEASES OF THE NERVOUS SYSTEM (ICD-10 G00-G99)

The neurologic outcomes reviewed in this section are amyotrophic lateral sclerosis (ALS), peripheral neuropathy, and other neurologic outcomes.

Amyotrophic Lateral Sclerosis

ALS is a neuromuscular disorder; it is often referred to as Lou Gehrig’s disease and might also be called motor neuron disease or Charcot’s disease. It affects approximately 20,000 to 30,000 people in the United States (NINDS 2006; The ALS Association 2006). ALS affects all races and ethnic backgrounds and the risk is higher in men than women of the same age (Annegers et al. 1991). The disease is often relentlessly progressive and almost always fatal. The rate of progression is quite variable from patient to patient.

ALS causes degeneration of the motor neurons in the cerebral motor cortex (called upper motor neurons) and the brain stem and spinal cord (called lower motor neurons) (Rowland 2000). The motor neurons are nerve cells that provide communication between the highest levels of the nervous system and the voluntary muscles of the body (NINDS 2006). When the upper motor neurons degenerate, their connections to the lower motor neurons and spinal interneurons are disrupted. That disruption leads to weakness of muscles in a characteristic distribution and the development of spasticity. Lower motor neuron degeneration disrupts nerve contact to the muscles resulting in muscle atrophy. Spontaneous muscle activity, called fasciculation, occurs. Eventually, affected people are unable to move their arms and legs and cannot speak or swallow. When the connection is disrupted between the neurons and the muscles responsible for breathing, patients either die from respiratory failure or require mechanical ventilation to continue to breathe. The majority of persons with ALS die from respiratory failure within 5 years from the onset of symptoms. To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes (such as progressive muscular atrophies and varieties of peroneal muscular atrophy, Kennedy’s syndrome, or multifocal motor mononeuropathy).

Five to ten percent of ALS cases are familial (inherited) and the remainder are sporadic (Rowland 2000; Siddique et al. 1999). Only one parent needs to carry the mutant gene for ALS to occur in about half of the children in cases of familial ALS (NINDS 2006). The specific gene mutations causing the majority of familial ALS cases are unknown. However, about 20% of familial cases are believed to be caused by a mutation in a gene that encodes the enzyme superoxide dismutase 1 (NINDS 2006).

The cause of sporadic ALS is unknown. Despite a number of epidemiologic studies examining occupation (for example, Italian professional soccer players, farmers, and electricians), physical trauma, strenuous physical activity, lifestyle factors (for example, diet, body mass index, cigarette use, and alcohol consumption), ethnic group, and socioeconomic status, there are no consistent findings (Armon 2003; Armon 2004a; Chio et al. 2005; Rowland 2000; Valenti et al. 2005). It has been suggested that the risk of ALS may decrease with decreasing latitude (north-south gradient of risk) (McGuire et al. 1996a).



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