# Exercise as it relates to Disease/Exercise and its effects on Amyotrophic Lateral Sclerosis (ALS)
## Background
### What is Amyotrophic Lateral Sclerosis?

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease in the United States, is the most common adult motor neuron disease. The disease is rapidly progressive and invariable fatal as it attacks the nerve cells (neurons) responsible for controlling voluntary muscles (various muscle actions we have control over, such as those in our arms, legs and face). Since ALS is characterized by the gradual degeneration and death of motor neurons, it is categorized into a group of disorders known as the motor neuron diseases.

### Prevalence

The average incidence of ALS is 2 cases per 100,000/year. The actual prevalence being 6 per 100,000/year, which is 2 to 3 times greater than the incidence.

### Causes of ALS

Approximately 85-90% of cases are sporadic, meaning they have no genetic component, the remaining 5-10% of cases are inherited (familial). So far 11 genes have been identified as associated with the disease. The most studied gene encodes for copper/zinc superoxide dismutase enzyme (SOD1). Both forms of ALS are clinically and pathologically similar. The typical age for both forms is between 50 and 60 years. Causes for most cases of ALS are unknown and the clinical course is highly variable, suggesting that multiple factors underlie the disease mechanism.

## Mutated SOD1

The most widely researched mutation leading to ALS is the cystolie antioxidant enzyme Cu/Zn-SOD (SOD1). 20-30% of familial ALS (FALS) cases are caused by the dominant inheritance of mutations in the SOD1 gene. These mutations occur outside the active site of the SOD1 enzyme, modify the stability of the protein backbone, and lessen the enzyme's affinity of Zinc Though it is still not clear as to how mutations in the SOD1 gene lead to motor neuron degeneration, increasing evidence suggests that mutant SOD1 protein can become toxic.

## Effects of ALS

The disease's primary characteristic is the selective dysfunction and death of the neurons in the motor pathways. The shutdown of these neurons lead to:
* Fasciculations, cramps, tight and stiff muscles (spasticity)
* Hyperreflexia (exaggerated reflexes) including an overactive gag reflex - usually occurring in the upper motor neurons
* Generalized weakness
* Muscle atrophy
* Paralysis - usually occurring in the lower motor neurons
* Slurred and nasal speech, or difficulty chewing or swallowing
Failure of the respiratory muscles is generally the fatal event, occurring within one to five years of the onset of the disease. If symptoms occur in the arms or legs first, it is referred to as "limb onset" ALS. Other patients first notice speech problems, this is termed "bulbar onset" ALS.

## Current Rehabilitation Methods

| Rehabilitation Method | Effects |
| Riluzole (Rilutek) | Reduces damage to motor neurons, but does not reverse effects, by decreasing the release of glutamate. Can prolong survival for several months, mainly for those having difficulty with swallowing. |
| Prescribed medications | Reduce fatigue, ease muscle cramps, control spasticity, and reduce saliva or phlegm |
| Gentle, low impact aerobic exercise | Strengthen unaffected muscles, improve cardiovascular health, & help patients fight fatigue or depression |
| Nutritional Support | Plan and prepare numerous meals throughout the day that provide enough calories, fiber and fluid, and how to avoid foods that are difficult to swallow |
| Mechanical ventilation (respirators) | Ease problems with breathing and prolong survival |

## Exercise as an ongoing recovery intervention

| Flexibility | Strength | Aerobic exercise |
| Improves *helps avoid the development of contractures (found in knees, ankles and shoulders) *useful for spasticity - reduces the risk of falling Impact of Quality of Life *Improves patient's self-sufficiency & gives ability to perform daily activities Main Goal *To improve range of motion aids *Relieve muscle tightness | Improves *absolute muscle strength *delaying muscle loss Impact of Quality of Life *Allows patients to become more self-sufficient, giving them the ability to perform daily activities Main Goal *Maximize the strength of the affected muscles | Improves *increases overall oxygen consumption, with proportional increases in heart rate *slows deterioration on the ALS functional rating scale Impacts of Quality of Life *perform daily activities without fatigue *reduces depression & psychological issues *reduces/decreases risk of chronic conditions (i.e. obesity and excessive weight gain) Main Goal *to reduce fatigue levels and to enhance standard of living in some patients. |

## Recommendations for Effective Exercise Rehabilitation

| Exercise | Recommended Activities from the Muscular Dystrophy Association |
| Range of Motion | At least 10 minutes a day performing stretching and range of motion activities, especially in areas of weakness or tightness. Aim to perform every day, even if assistance is required. |
| Aerobic | 30 minutes of low impact, low intensity exercise (walking, swimming, bicycling & aerobic type fitness classes). Ensure 5–10 minutes is included. Aim for 3–4 days a week. |
Before undertaking any exercise, patient must be prescreened. Any medications, strength, range of motion, level of fitness must be taken into consideration while developing a program for ALS patient. Ensure program and designated activities is cleared by a physician or physiotherapist, and that all activities are supervised.

## Improving Compliance

* Involvement, support and interaction from patient's family, community and healthcare professionals
* Providing a positive outlook and interest in prescribes exercises will increase levels of motivation
* Altering activities to reduce exercise-related pain
* Prescribing activities that suit the patient's interests
* Creating a programs that suits the patient's daily schedule.

## Further reading

* Amyotrophic Lateral Sclerosis (ALS) Fact Sheet
* Drory, V, Goltsman, E, Reznik, J, Mosek, A, & Korczyn, A 2001, 'The value of muscle exercise patients with amyotrophic lateral sclerosis', Journal of the Neurological Sciences, Vol. 191, pp. 133–137.

## References

* 1 2 3 4 Bruijn, L, Miller, T & Cleveland, D 2004 'Unraveling the mechanisms involved in motor neuron degeneration in ALS', Annual Review of Neuroscience, Vol. 27, pp. 723-749.
* ↑ Delisle, M & Carpenter, S 1984, 'Neurofibrillary axonal swellings and amyotrophic lateral sclerosis', Journal of Neurological Science, Vol. 63, pp. 505-512.
* 1 2 3 4 Lopes de Almeida, J, Silvestre, R, Pinto, A, & de Carvalho, M 2012, 'Exercise and amyotrophic lateral sclerosis', Neurological Science, Vol. 33, pp. 9-15.
* 1 2 Patel, B & Hamadeh, M 2009, 'Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis', Clinical Nutrition, Vol. 28, pp. 604-617.
* 1 2 Rosen, D, Siddique, T, Patterson, D, Figlewicz, D, Sapp, P, & Hentati, A 2009, 'Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis' Nature, Vol. 362, pp. 69-62.
* ↑ Deng, H, Hentati, A, Tainer, J, Iqbal, Z, Cayabyab, A, & Hung, W 1993, 'Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase', Science, Vol. 261, pp. 1047-1051.
* ↑ Borchelt, D, Lee, M, Slunt, H, Guarnieri, M, Xu, Z, & Wong, P 1994, 'Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity', Proceedings National Academy Science USA, Vol. 19, pp. 8292-8296.
* ↑ Crow, J, Sampson, J, Zhuang, Y, Thompson, J, & Beckham, J 1997, 'Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysts of tyrosine nitration by peroxynitrate', Journal of Neurochemistry, Vol. 69, pp. 1936-1944.
* ↑ Borchelt, D, Guarneiri, M, Wong, P, Lee, M, Slunt, & H, Xu, Z 1995, 'Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function', Journal of Biology and Chemistry, Vol, 270, pp. 3234-3238.
* ↑ Mulder, D, Kurland, L, Offord, K, & Beard, C 1986, 'Familial adult motor neuron disease: amyotrophic lateral sclerosis', Neurology, Vol. 36, pp. 11-17.
* ↑ Gonzalez de Aguilar, J, Echaniz-Laguna, A, Fergani, A, Rene, F, Meininger, V, & Loeffler, J 2007, 'Amyotrophic lateral sclerosis: all roads lead to Rome', Journal of Neurochemistry, Vol. 101 pp. 1153-1160.
* 1 2 Muscular Dystrophy Association - ALS Division, 2010, Everyday Life with ALS: A Practical Guide, MDA ALS Division, Tucson, AZ.