What is amyotrophic lateral sclerosis?

Causes and Symptoms

Amyotrophic lateral sclerosis (ALS) plagues twenty thousand Americans, with five thousand cases newly diagnosed each year. In spite of extensive epidemiological, controlled, and clinical research, the cause or causes of ALS are unknown. In most cases, it does not run in families, there are no known risk factors, and it does not seem to develop following exposure to toxins, radiation, or any particular environmental sources. Diet appears to have no effect. It appears to occur at random, while tending to strike individuals between the ages of forty to sixty, and it is more common in men than women.

However, 5 to 10 percent of all ALS cases are inherited in what is referred to as “the familial form.” Of these familial cases, 20 percent may have a mutation in the gene responsible for the production of superoxide dismutase 1 (SOD1). Nonetheless, this finding does not explain most other cases.

ALS researchers have also noted the presence of increased glutamate in the spinal cord and serum in some familial and nonfamilial cases. They theorize that its existence may play a key role in the mechanism of nerve damage. Other theories about what causes ALS assign important roles to the body’s own immune system, suggesting that ALS may essentially be an autoimmune disease, similar in mechanism (if not effect) to lupus.

The signs and symptoms of ALS are almost always gradual and subtle in its early stages. People may begin occasionally to slur speech, spill food, or experience weakening grip. Oddly, but not particularly troublingly, their feet may miss stairs and their fingers may miss the correct keys when typing. They tend to report that they are becoming clumsy and unsteady, their penmanship is worsening, and their limbs are weakening. Frequently, people put up with these early signs believing they will go away spontaneously, or that they are the result of fatigue, an undiagnosed infection, or the side effects of medication. Further along this early stage, however, fasciculation and spasticity commonly become clinically evident due to both upper and lower motor neuron damage.

For the neurological specialist, the key to diagnosing and differentiating ALS from other motor neuron disorders is the presence of simultaneous upper and lower motor neuron damage. The diagnosis of ALS is made because other, more common, motor neuron diseases have been excluded. This exclusion is important because several of these diseases mimic ALS but are far more treatable.

There are several diagnostic procedures helpful in determining the patient’s diagnosis. Electromyography
(EMG) is a diagnostic technique that detects electrical activity in the muscles. Specific EMG patterns and findings can be diagnostic of ALS, though not all patterns are clear, distinct, and unambiguous. Nerve conduction studies are also used to help differentiate ALS from peripheral neuropathy or myopathies. Magnetic resonance imaging
(MRI), a procedure commonly used for helping to diagnose many conditions, provides visual images of the brain and spinal cord. While MRI readings are usually unremarkable in ALS patients, an MRI is often ordered to help the physician decide that the troubling symptoms are not from another disorder, evident in an abnormal or significant MRI reading.

The progression of the disease varies widely from individual to individual; however, the course or stages of deterioration remain fairly universal. As the disease progresses and attacks voluntary motor functions, patients develop increasing difficulty with walking, swallowing, talking, and dressing themselves. Further along, patients may need more aggressive support with feeding tubes and mechanical ventilators.

Perhaps the most insidious aspect of ALS is that while voluntary muscles deteriorate, thinking and emotions remain completely unaffected. Individuals are aware of the entire disease process, loss of independence, and decreasing ability to express themselves. Perhaps even more important than the medical management of the disease is the attention to the existential, psychological, and family challenges that ensue.

Treatment and Therapy

There is no specific treatment or cure for ALS. The mainstays of therapy rely on supportive assistance with mobility and communication, symptomatic relief, and comfort measures. Medications such as riluzole (Rilutek) can decrease the release of glutamate, and a few studies have shown that riluzole may prolong survival and slow the rate of deterioration. Unfortunately, it does not halt or reverse neuron damage.

Not much pain accompanies ALS. More problematic are feelings of stiffness, soreness, and discomfort. Both pharmacologic and nonpharmacologic treatments can bring symptomatic relief of spasticity, fatigue, and fasciculations, significantly improving patients’ comfort and quality of life.

Allied health care providers such as physical, occupational, and speech therapists play a large role in helping keep patients, and often their families, functional, maintaining independence and mobility as much as possible. As muscle weakness progresses, assistive devices such as communication and sign boards, leg splints, and wheelchairs may be needed. Mental and behavioral health specialists, as well as hospice programs, provide much needed support and relief for both patients and family members, who are typically the caregivers of the ALS patient.

Perspective and Prospects

Scientists are searching for a biological marker for ALS. Such a discovery may yield a method of early detection and possible prevention. An interesting case study presented a scenario that ALS may be associated with a virus. A patient with acquired immunodeficiency syndrome (AIDS) was simultaneously diagnosed with ALS. Treatment with antiviral AIDS therapy combated the signs and symptoms of ALS as well. This critical observation may link ALS to a viral cause and possible cure. However, far more research needs to be done. In April 2013, researchers discovered that RNA lariats may help prevent nerve degeneration in ALS patients.

In conclusion, ALS is a varyingly progressive degenerative neurologic disorder. At this time, there is no cure or treatment. Comfort measures and supportive care are the mainstay of treatment for patients and their families. Providing both physical and emotional support is crucial to both. National and local support agencies offer multiple services to assist them.

Bibliography

ALS Association. http://www.alsa.org.

Armakola, et al. "Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models."  Nature Genetics. 12. (2012): 1303–1311. Print.

Feigenbaum, David, ed. Journeys with ALS. Virginia Beach, Va.: DLRC Press, 1998.

Kimura, Jun, and Ryuji Kaji, eds. Physiology of ALS and Related Diseases. New York: Elsevier Science, 1997.

McFarlane, Rodger, and Philip Bashe. The Complete Bedside Companion: No-Nonsense Advice on Caring for the Seriously Ill. New York: Simon & Schuster, 1998.

Mitsumoto, Hiroshi, and Theodore L. Munsat, eds. Amyotrophic Lateral Sclerosis: A Guide for Patients and Families. 3d ed. New York: Demos Health, 2009.

Oliver, David, Gian Domenico Borasio, and Declan Walsh, eds. Palliative Care in Amyotrophic Lateral Sclerosis. 2d ed. New York: Oxford University Press, 2006.

Parker, James N., and Philip M. Parker, eds. Official Patient’s Sourcebook on Amyotrophic Lateral Sclerosis. San Diego, Calif.: Icon Health, 2003.