Amyotrophic Lateral Sclerosis

An Introduction

View of boy's back, close-up on spine
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Amyotrophic lateral sclerosis (ALS), sometimes known as Lou Gehrig's disease after the famous baseball player, is a condition that causes a person to become gradually and progressively weaker. This progressive weakness is due to degeneration of nerves in the anterior horn of the spinal cord, which transmits information from the brain to the muscles of the body.

As these nerve cells die, the muscles they communicate with begin to atrophy.

In addition, neurons in the brain also die, although the dying neurons usually are not related to how a person thinks, so the person will likely remain aware of how the disease is progressing. In most cases, ALS leads to paralysis and death within five years. About ten percent of the time, people with ALS survive for a longer time.

ALS usually affects people when they are between 40 and 70 years of age; however, it can occur at other times in a person's life. Men are affected more often than women. Fortunately, ALS is relatively rare, afflicting about 30,000 people in the United States, with approximately 5,600 new cases of ALS diagnosed every year.

Symptoms of ALS

Symptoms of ALS usually start with weakness. This weakness may begin with just one limb. Muscles may cramp, stiffen or have a twitching called "fasciculations." If the legs are affected first, the person may begin to notice they are tripping more often or they may feel clumsier.

If symptoms start in the hands, there may at first be some difficulty handling small objects, such as buttoning a shirt or turning a key. Less common, the first muscles to be affected are those in the face and throat, leading to difficulty speaking or swallowing. There is no tingling or numbness associated with this weakness.

As the disease progresses, the weakness will worsen and spread to other areas of the body. The person will lose the ability to speak as he or she loses control of their tongue and lips. Eventually, the person may require a feeding tube. As the muscles needed for breathing weaken, respiratory support may be provided, first with a CPAP machine and then with mechanical ventilation. Because they do not have the strength to cough or clear their throats, people with advanced ALS are prone to aspiration pneumonia. In fact, most people with ALS will ultimately pass away due to aspiration or respiratory failure.

Occasionally, people with ALS have an associated dementia. Also, some people develop a pseudobulbar palsy, which makes it difficult for them to control their emotions.

What Causes ALS?

The exact causes of ALS are still being researched. The disease usually seems to strike spontaneously, though about 10 percent of cases are genetic. A gene that codes for superoxide dismutase (SOD1), an enzyme that breaks down free radicals, was discovered in 2001.

Other genes - including TAR DNA-binding protein (TARDBP, also known as TDP43); fused-in-sarcoma (FUS), a genetic abnormality on chromosome 9 (C9ORF72); and UBQLN2, which encodes the ubiquitin-like protein ubiquitin?2 - have all been associated with ALS.

As a result of these mysterious cellular changes, the nerve cells in the anterior horn of the spinal cord and cells in the cerebral cortex begin to die.

Some people have noted a possible link between head injuries and an increased risk of ALS, although these cases may actually represent a different disorder known as chronic traumatic encephalopathy. Military veterans, especially those who served in the Gulf War, have an increased risk of developing ALS symptoms, as do some athletes. Exposure to toxins has also been investigated, though nothing conclusive has yet arisen.

How Is ALS Diagnosed?

The diagnosis of ALS should be done by a neurologist. Neurologists who evaluate motor neuron diseases such as ALS may speak of a combination of "upper and lower motor neuron signs" required to make the diagnosis. Certain physical exam findings, such as hyperactive deep tendon reflexes, suggest that the weakness is due to disease in the spinal cord or brain. Other exam findings, such as fasciculations, are usually attributed to damage to a nerve after it has left the spinal cord. Because motor neuron diseases like ALS damage the area where upper motor neurons descending from the brain communicate with lower motor neurons exiting the spine, both upper and lower motor neuron signs are seen in ALS and are required for the diagnosis.

The seriousness of a diagnosis of ALS usually leads to additional testing to exclude other, more treatable, diseases that can mimic ALS. An electromyogram (EMG) and nerve conduction study may be done to exclude the possibility of diseases such as myasthenia gravis or peripheral neuropathy. An MRI scan may be done to exclude other spinal cord diseases, such as tumors or multiple sclerosis.

Depending on the individual person's story and physical exam, additional tests for such diseases as HIV, Lyme or syphilis may be performed. Patients diagnosed with ALS should strongly consider getting a second opinion.

How Is ALS Treated?

Only one medication, Riluzole, has been shown to be at all effective in improving the survival of patients with ALS. Unfortunately, the effect is modest, prolonging survival only by an average of three to five months.

But there is help. Working with a team of medical professionals can help relieve many of the symptoms of ALS. Such a team could include a neurologist, physical therapists, speech and occupational therapists and experts in nutritional and respiratory equipment.

Social workers may be involved in helping arrange for support groups as well as legal necessities, such as a living will and power of attorney. Especially near the end of life, many patients benefit from working with experts in palliative care and hospice.

Working with qualified professionals can help patients with ALS live the rest of their lives as independently and comfortably as possible.

Sources:

AE Renton, E Majounie, A Waite, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011;72(2): 257-68. E-pub 2011 Sep 21.

HX Deng, W Chen, ST Hong, KM Boycott, GH Gorrie, SN Siddique, Y Yang, F Fecto, Y Shi, H Zhai, H Jiang, M Hirano, E Rampersaud, GH Jansen, S Donkervoot, EH Bigio, BR Brooks, K Ajroud, R Sufit, JL Haines, E Mugnaini, MA Pericak Vace, T Siddique, Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia, Nature 477, pp 211-215 Sep 8, 2011

AC McKee, BE Gavett, RA Stern, CJ Nowinski, RC Cantu, NW Kowall, DP Perl, ET Hedley-Whyte, B Price, C Sullivan, P Morin, HS Lee, CA Kubilus, DH Daneshvar, M Wulff, AE Budson. TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy. J Neuropathol Exp Neurol. August 2010

AH Ropper, MA Samuels. Adams and Victor's Principles of Neurology, 9th ed: The McGraw-Hill Companies, Inc., 2009.

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