ALS is primarily a disease of the parts of the nervous system that control voluntary muscle movement. The word “amyotrophic” comes from Greek roots that mean “without nourishment to muscles” and refers to the loss of signals nerve cells normally send to muscle cells. “Lateral” means “to the side” and refers to the location of the damage in the spinal cord. “Sclerosis” means “hardened” and refers to the hardened nature of the spinal cord in advanced ALS.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons leading to progressive weakness of the limbs, bulbar muscles, and respiratory muscles. Fifty percent of patients die within 3 years after onset of symptoms, mainly due to respiratory failure.
Synonyms: ALS (Amyotrophic Lateral Sclerosis), Charcot’s disease, Lou Gherig’s disease, Motor neuron disease
What causes ALS?
Although ALS is clearly “familial,” or “inherited,” only 5 to 10 percent of the time, genetic factors probably play a role in ALS in many people in whom the disorder does not appear to be inherited. It may be that genes that aren’t directly involved in causing ALS can contain variations that increase or decrease the likelihood of developing the disease in the presence of as-yet-uncertain environmental factors.
A common feature in ALS is the presence in nerve cells of improperly folded proteins that clump together, forming “aggregates.” In people with ALS, misfolded versions of proteins known as SOD1, FUS and TDP43 are frequently seen, even when there is no genetic abnormality in the DNA for these proteins. (If there is a genetic abnormality, they’re even more likely to misfold.)
Free radicals are molecules that carry electrical charges that make them unstable and liable to damage cellular structures. They’re a normal part of cellular life, and cells are usually able to neutralize most of them and keep their numbers in check. But in ALS, free radicals may build to toxic levels and damage cells, through an attack process called “oxidative stress.”
Glutamate is a common chemical in the nervous system, which neurons use to send signals to other neurons. But, like many things, glutamate has to be present in the right amount to work: Too little leads to a lack of signaling and too much to the death of nearby nerve cells.
Evidence from studies of people with ALS points to an overabundance of glutamate in the nervous system. This may result from inadequate transport of glutamate away from nerve cells after it has finished its signaling work.
Most cells have a built-in “suicide” program known as “programmed cell death,” or “apoptosis.” Under some circumstances, programmed cell death is normal. But in ALS and other degenerative diseases, it’s possible that the cell death program is activated inappropriately.
Immune system abnormalities
Many disorders that affect the nervous system are “auto immune”in nature, meaning they occur when the body’s immune system mistakenly attacks its own tissues. Microglia, immune system cells found in the nervous system, appear to play a role in ALS. None of the medications that are helpful for other autoimmune diseases has been effective against ALS so far, but some are being tested now, and new ones are in development.
Specific genes associated with ALS
Among the specific genes that, when flawed, can cause ALS and have received a great deal of attention by MDA-supported researchers, are:
• SOD1 • C9ORF72 • FUS • TDP43
What happens to someone with ALS?
In ALS, nerve cells that control muscle cells gradually die. In most cases, the cause is unknown. As these motor neurons die, the muscles they control become weak and then nonfunctional. Eventually, the person with ALS may become paralyzed.
Without assistive technologies such as mechanical ventilation and feeding tubes, the average life expectancy is three to five years after an ALS diagnosis. About 4 to 10 percent of those with the disease live more than 10 years, and some survive for decades, such as British physicist Stephen Hawking, who has had ALS since the 1960s and is still able to practice his profession.
Modern technology has allowed people with ALS to compensate to some degree for almost every loss of function, making it possible even for those with almost no muscle function to continue to breathe, communicate, eat, travel and use a computer. It’s important to note that the involuntary muscles, such as those of the heart, gastrointestinal tract, bowel and bladder, and those that regulate sexual functions are not directly affected in ALS. (However, prolonged inability to move and other effects of ALS can have some indirect impact.) Hearing, vision and touch generally remain normal.
ALS-associated pain can occur as a result of tightness (spasticity) of muscles, decreased range of motion of the joints, and abnormal stresses on the muscles, bones and skin that occur as a result of immobility. Pain and its management should always be discussed with your health care professionals.
Mild cognitive impairment is not uncommon, but severe cognitive impairment, known as “dementia,” occurs in only about 3 to 5 percent of cases. Some with ALS may experience involuntary laughing or crying spells that are unrelated to their emotional state. Called involuntary emotional expression disorder, or “pseudobulbar affect,” this symptom can be treated with medication.
Who gets ALS?
ALS usually strikes in late middle age (the average age of onset in the United States and Europe is between 56 and 63) or later, although ALS also affects younger adults and even children, as well as very elderly people. Some genetic forms of ALS have their onset in youth.
Men are somewhat more likely to develop ALS than are women. Studies suggest an overall ratio of about 1.5 men to every woman who develops the disorder in Western countries. In younger-onset patients, there seems to be a greater male predominance.