Introduction to Amyotrophic Lateral Sclerosis and Exercise
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a fatal, progressive, degenerative motor neuron disease characterized by the aggregation of ubiquinated proteins in the affected motor neurons. There are three forms of ALS: “familial” (hereditary), “sporadic” (nonhereditary), and “ALS/dementia” (ALS that targets the brain). Sporadic ALS is the most common form of the disease (80-90% of call cases), and familial ALS occurs in about 5% of cases (Byrne et al., 2011). The cause of ALS is still not completely understood, but has been linked to three primary genes: SOD1, encoding CuZn superoxide Dismutase (Rosen, 1993); ANG, encoding angiogenin (Conforti et al., 2008; Greenway et al. 2006; Paubel et al., 2008); and TARDP, encoding TAR DNA binding protein TDP-43 (Sreedharan et al., 2008). However, there are a variety of other genes suggested to cause ALS in some cases (Al-Chalabi et al., 2012; Kim et al., 2013).
ALS affects both upper and lower motor neurons. The motor neurons in the spinal cord, brain stem, and cerebral motor cortex degenerate, resulting in a variety of signs and symptoms. The disease is characterized by the absence of sensory symptoms and findings.
Seventy percent of patients experience initial symptoms with leg, arm, or bulbar (muscles used for swallowing) muscle focal weakness. Lower-extremity motor neuron clinical signs include muscle weakness, muscle atrophy, fasciculations (muscle twitches), hyperreflexia, hypotonicity, and muscle cramps. Upper-extremity motor neuron clinical signs include spasticity, hyperreflexia, and pathological reflexes. Bulbar signs include dysarthria, dysphagia (difficulty swallowing), sialorrhea (drooling), and pseudobulbar palsy (Dal Bellow-Haas et al., 1998). Cognition, extra-ocular eye movements, and autonomic, bowel, bladder, and sexual functions usually remain intact (Dal Bellow-Haas et al., 1998, Goldman & Bennett, 2000).
For a definite diagnosis of ALS, the body is divided into four regions:
- bulbar - jaw, face, palate, larynx, and tongue;
- cervical - neck, arm, hand, and diaphragm;
- thoracic - back and abdomen; and
- lumbosacral - back, abdomen, leg, and foot (Goldman & Bennett, 2000).
A definite diagnosis is made when upper and lower motor neuron signs are present in the bulbar region and two other spinal regions, or in three spinal regions. Individuals with motor neuron signs in only two spinal regions are classified as having probable ALS. Possible ALS is the diagnosis if dysfunction is present in only one region, or if a patient presents with only upper motor neuron signs in two regions, or if lower motor neuron signs are found in the upper-extremity muscles (Goldman & Bennett, 2000).
Muscle weakness progresses over time; the pattern and rate of deterioration vary widely. ALS has an incidence rate of two to four people in 100,000 (Goldman & Bennett, 2000). It is slightly more common in men than women, with the average age of onset in the mid-50s (Dal Bellow-Haas et al., 1998). The duration of the disease, from onset of symptoms until death, is 27 to 43 months; the average 5-year survival rate is 25% (Goldman & Bennett, 2000). However, about 10 percent of ALS patients survive for 10 or more years. Death is usually due to respiratory failure, which occurs approximately 3 years after symptoms from ALS are experienced (Shaw et al., 2001).
The cause of sporadic ALS is unknown. In a case study by Dal Bellow-Haas et al. (1998), a breakthrough in ALS research found that the disease may be caused by a mutation in the superoxide dismutase-1 (SOD1) gene. This would confirm studies by Bredesen et al., (1997); Bowling et al., (1993); and Kawamata, J. et al., (1997) that suggest that ALS is caused by free-radical injury.
Risk factors, such as head trauma, military deployment, excessive physical exertion, professional sports, and chronic head trauma have been suggested to be linked with ALS; the majority of the literature has shown strong positive associations with only a few risk factors:
- Exposure to hazardous chemicals / heavy metals
- Oxidative stress
- Smoking (for women only)
Pesticide exposure (Malek et al., 2012) and lead (D’ Amico et al., 2013) have been suggested to be linked with increased risk of ALS. However, the association is moderate and there are inconsistencies in the literature. Though the cause of oxidative stress is unknown, there is broad evidence that suggests oxidative damage detriments the pathogenesis of sporadic ALS (D’Amico et al., 2013). It is still unclear whether oxidative stress is a causal factor or a merely secondary effect of ALS. Vitamin and mineral intake may offer protective-effects against the onset of ALS. A pooled analysis by Fitzgerald and colleagues (2013) examined the association between nutrient intake and risk of ALS from a compilation of 5 different studies, totaling 1,100,910 participants with ALS. Their findings suggested that consumption of foods high in carotenoids (carrots, sweet potatoes, spinach, kale, tomatoes, greens, etc.,) may aid in the prevention or delay of ALS. The authors did comment that their results were based solely on dietary intake and not supplementation (Freedman et al., 2013). Beta-carotene supplements have been associated with increased risk of cancer at different sites. Thus, current evidence suggests that an individual should not supplement beta-carotene, and instead focus on nutrients from their dietary intake. Vitamin E has also been suggested to have similar protective effects against ALS (Wang et al., 2011; Michal Freedman et al, 2013), but further research is needed.
While the overall relationship between smoking and ALS appears weak (Alonso et al., 2010a), smoking has been strongly associated with ALS risk and poorer survival rates in women but not men (Alonso et al., 2010b).
Although severe depression is not a highly prevalent in persons with sporadic ALS (McElhiney et al., 2009), people who do experience psychological stress in the form of hopelessness, depression, and mental stress have shorter survival (McDonald et al., 1994). Positive moods are associated with longer durations of survival (6 months) (Johnston et al., 1999). It is possible that psychological stressors contribute to the biological changes, such as oxidative stress, that enhance the onset and progression of ALS. Though, more longitudinal studies must be conducted to solidify these findings.