Understanding ALS: Causes, Symptoms & What to Expect

How ALS (Lou Gehrig's Disease) Works Browse the article How ALS (Lou Gehrig's Disease) Works

ALS Overview

In 1934, Lou Gehrig was a legend in the baseball world. He had achieved a .363 batting average with the New York Yankees, hitting 49 home runs and earning 165 RBIs that season. No other player up to that time had scored as many RBIs.

But then in the 1938 season, while he should still have been in his prime, Gehrig started to slip. On opening day against the Red Sox, he couldn't get a single hit. When he did start hitting again, the balls weren't going nearly as far as they once had. Pitches that he would have hit out of the park in years past barely got him on base. During the '38 season, he batted below .300 for the first time in more than a decade, and his once strong stride turned into an old man's shuffle.

With his strength deteriorating, Gehrig finally went to the Mayo Clinic in Rochester, Minn., to get checked out. Doctors there gave him the news: He had amyotrophic lateral sclerosis (ALS), a degenerative disease that affects muscle nerve cells. After Gehrig's death on June 2, 1941, the disease would come to bear his name colloquially.

The reason Lou Gehrig had become so weak wasn't that his muscles weren't workin­g properly, but that his body had stopped sending the signals to move his muscles. ALS attacks motor neurons, the nerve cells that control voluntary movements (such as raising the arms or walking). There are two types of motor neurons: upper and lower. Upper motor neurons send messages from the brain to the spinal cord. Lower motor neurons carry the messages from the spinal cord to the muscles, telling them to move.

In the word "amyotrophic," "myo" means "muscle" and "trophic" means "nourishment." In ALS, a lack of nourishment to the motor neurons causes them to die. When motor neurons die, they can no longer send messages to the muscles to move. Because they can't move, the muscles atrophy and people with the disease eventually become paralyzed.

ALS isn't the only disorder that affects motor neurons. It's part of a group of motor neuron diseases that includes progressive muscular atrophy, primary lateral sclerosis and progressive bulbar palsy.

Causes of ALS: Who Gets ALS, and Why?

ALS is extremely rare, affecting only about two out of every 100,000 people, according to the ALS Association [source: ALSA]. About 5,600 people are diagnosed with the disease in the U.S. each year, and between 20,000 and 30,000 people live with it at any one time [source: ALSA].

What exactly causes ALS isn’t known, but researchers are learning more about the disease all the time. In most cases (90 to 95 percent), there is no known cause, and the disease is called sporadic ALS. In the remaining cases (5 to 10 percent), the disease is passed down through families, and is called familial ALS. A child who is born to someone with familial ALS has a 50 percent chance of also getting the disease [source: ­­ALSA].

Researchers have been looking for the gene or genes responsible for familial ALS, and in 1993, they made a huge breakthrough. They discovered a change or mutation in a gene called superoxide dismutase (SOD1). When the gene is normal, it directs the production of an enzyme that protects the motor neurons from damage caused by unstable molecules called free radicals. When the gene is mutated, the enzyme can’t protect the motor neurons, and they become damaged by the free radicals. About 20 percent of people with familial ALS have the SOD1 gene mutation. Researchers are still looking for more genes that might be involved.

Researchers also know that ALS is most common in Caucasian males, and it often starts when people are between the ages of 40 and 60 (although it can strike at an earlier age). People with ALS have too much of a substance called glutamate in their blood and spinal fluid. This chemical messenger helps nerve cells in the brain and spinal cord communicate with one another, but in large amounts it can actually damage motor neurons.

Researchers have speculated on several other possible causes of ALS, including:

• An autoimmune response, in which the body mistakenly attacks its own motor neurons
• Exposure to toxic substances or viruses
• An abnormality of the immune system that leads to inflammation in the brain and spinal cord
• A lack of certain nutrients in the diet
• Trauma

However, there isn't enough evidence from scientific research to prove any of these theories.

Are Gulf War Veterans at Risk?

Although it can be devastating, ALS is fortunately a rare disease. So researchers were surprised to find a startling number of cases among veterans of the 1991 Gulf War. Robert Haley of the University of Texas Southwestern Medical Center at Dallas discovered 20 cases of ALS in 690,000 Gulf War veterans, which is about equal to 1 out of every 34,500 people (the normal rate of ALS is 1 out of every 50,000 people) [source: Ha­ley]. Also unusual was that 17 of the veterans were diagnosed before age 45 -- a rate three times that of other people their age [source: ­­Ha­ley]. Haley’s theory is that the disease might have been triggered by exposure to nerve agents during the war, and that people who developed ALS lacked an enzyme needed to protect their motor neurons from that damage.

ALS Symptoms and Diagnosis

When ALS begins, its symptoms are often hard to notice. Some people may become clumsier than usual. Others may experience muscle weakness or stiffness. Still others may slur their words.

Which symptoms appear first depends on the muscles affected. When the disease damages lower motor neurons, muscles in a particular part of the body (like the hand or foot) will be affected. When ALS impacts upper motor neurons, people will experience general clumsiness, slurred speech and difficulty swallowing. Eventually, the disease will spread to all of the body's muscles and lead to total paralysis.

In the early stages of the disease, symptoms may include muscle weakness in one part of the body (an arm or leg); clumsiness, such as tripping and dropping things; difficulty speaking or swallowing; muscle twitches (fasciculations) and cramps; fatigue in the arms or legs; weight loss and the loss of muscle mass; and uncontrolled laughing or crying, called emotional incontinence.

How the disease progresses varies from person to person. But as it worsens, people may experience shortness of breath or difficulty breathing, stiff muscles and exaggerated reflexes (including a strong gag reflex).

Eventually people may lose the ability to breathe on their own and will need to be put on a ventilator. Most people with the disease eventually die from respiratory failure or pneumonia -- because they can't swallow properly, they aspirate food and fluid into the lungs.

While ALS can devastate the body, it doesn't affect involuntary muscles (such as bowel and bladder function), the senses (smell, taste, hearing and sight), or the ability to think.

ALS isn't an easy disease to diagnose. Its symptoms mimic those of other diseases (such as Parkinson's) and there isn't one test to spot it. Often doctors will rule out other diseases to arrive at a diagnosis. For the very small percentage of people with familial ALS, there's a genetic test to look for the faulty SOD1 gene. However, because most people with ALS don't have this gene, the test isn't very useful.

Some tests that are used to diagnose ALS include:

• Electromyogram (EMG) inserts a thin electrode into the muscle to detect electrical activity and see how well the muscles are working.
• Nerve conduction velocity (NCV) passes a small shock through a nerve to measure the speed of nerve signals.
• Spinal tap inserts a needle into the spinal canal and removes fluid (cerebrospinal fluid) for testing.
• X-rays, CT scans and MRI create images of the brain and spinal cord to look for any abnormalities.
• Blood and urine tests look for abnormal levels of certain substances in the blood and urine.
• Muscle or nerve biopsy removes a small sample of tissue, which is sent to a lab for testing.

Once a person is diagnosed, the average survival time is only three to five years. However, about 10 percent of people with ALS live for 10 years or more, and the lifespan for ALS patients is increasing as new treatments are introduced [source: ­ALSA].

Stephen Hawking

­­Most people who receive a diagnosis of ALS can expect to live just three to five years. British physicist Stephen Hawking has defied the odds, living for more than 45 years with the disease. Hawking was diagnosed at 21, while a graduate student at Cambridge University. He has been wheelchair-bound since the 1970s. In 1985, he developed pneumonia and had to have a tracheotomy operation, which robbed him of his ability to speak. When a computer whiz in California heard of Hawking's plight, he sent him a computer program called Equalizer that could speak for him. Since then, Hawking has become known for the synthesized, computer-generated voice that enables him to speak. Determined early on not to let the disease steal his life, Hawking went on to become one of the world's preeminent physicists. He published the best-selling book, "A Brief History of Time," and he has made great contributions to the fields of quantum gravity and cosmology.

ALS Treatment

Today there's no cure for ALS, but researchers are working in that direction. In the meantime, treatments are available to relieve symptoms and improve patients’ quality of life. One of the main therapies focuses on the chemical messenger, glutamate, which ALS patients produce in excess. The drug riluzole (marketed under the brand name Rilutek) decreases the release of glutamate to prevent it from damaging motor neurons. Although it can’t reverse the course of the disease, Rilutek can slow it down, and it has been shown in scientific studies to help ALS patients live for a few months longer than they would otherwise. Other medications help manage the symptoms of ALS -- for example, drugs that treat fatigue, muscle cramps, pain and sleep problems.

Other therapies that can help ALS patients include physical therapy and exercise such as walking, biking and swimming to improve strength and mobility in the unaffected muscles. A walker, brace or wheelchair can help people get around once they're no longer able to walk on their own. And a speech therapist can teach patients techniques to help them speak more clearly.

In some people with ALS, the disease simply stops progressing. It just “burns out.” Doctors don’t know why this happens.

Researchers are always looking for new ways to prevent and combat ALS. Here are a few of the breakthroughs on the horizon:

Researchers are looking for more genes that cause the disease, as well as the factors that cause motor neurons to die.

Scientists are testing out various substances in patients with ALS, including the enzyme SOD1, antioxidants and neurotrophic factors (chemicals in the brain and spinal cord that help neurons develop and protect them). Drugs that might one day be used to treat ALS include the antibiotic minocycline (Minocin), the breast cancer drug tamoxifen, and the antioxidant coenzyme Q10.

Stem cells are another active area in ALS research. In 2008, scientists were able to reprogram stem cells so that they formed healthy motor neurons. They took the cells from the skin of an 82-year-old woman and her 89-year-old sister, both of whom had the SOD1 gene mutation. Scientists hope they might one day be able to use stem cells to replace damaged motor neurons in ALS patients.

Charles Mingus

One of the great jazz musicians of the 20th century was afflicted with ALS. Charles Mingus was a multifaceted, multitalented musician. He was a virtuoso bass player, as well as a composer, bandleader and pianist. In the 1940s and '50s, he toured with such music greats as Louis Armstrong, Charlie Parker, Miles Davis and Duke Ellington. During his career, he recorded more than 100 albums. In 1977, Mingus was diagnosed with ALS. Refusing to let his illness stop his music, he continued to record from his wheelchair. Mingus sang his last work into a tape recorder. He died in 1979 at age 56.