What is amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that reduces and eventually eliminates patients' muscle control. It is commonly known as Lou Gehrig's disease after the famous baseball player who died of ALS in 1941.

ALS is a rare condition. Approximately 5,600 cases are diagnosed annually in the United States, according to the ALS Association. An estimated 30,000 Americans are living with the disease at any given time.

Patients who develop ALS lose control of their muscles as the neurons responsible for movement begin to die. In healthy bodies, motor neurons transmit signals from the brain, through the nerves and then to the muscles. This enables the muscles to move. When the nerves die, these muscles begin to waste away from the lack of use (atrophy). ALS affects motor neurons throughout the body, including those in the brain that control the muscles of speech, swallowing and facial expression, and those in the spinal cord that control other aspects of movement.

The impact of the disease usually is first seen in the patient's hands, arms or legs. The muscles become weak and the patient may lose fine movement control in the hands. This may affect everyday activities such as buttoning clothes and tying shoes. The disease continues to spread to other muscle groups, gradually reducing the patient's ability to move. Eventually patients become paralyzed due to muscle degradation. Most patients have no loss of mental function. However, some may develop dementia.

ALS is usually a fatal disease. It typically progresses until it causes death from respiratory failure, because the muscles that control breathing degrade. In some cases, patients experience a remission or halting of disease progression, but the mechanisms responsible for this phenomenon are not well-understood. According to the ALS Association, approximately 20 percent of ALS patients live five years or longer after the onset of symptoms, while 10 percent live longer than 10 years. However, most patients succumb to the condition approximately three to five years after diagnosis.

The disease can develop at almost any age, but most cases occur in the middle to later stages of life. The majority of patients notice the early symptoms of ALS between the ages of 40 and 70. Other individuals experience symptoms earlier, with some people developing the disease in their 20s. Men are 20 percent more likely than women to develop the disease early in life. However, disease occurrence in the later years of life is equal for men and women, according to the ALS Association.

The vast majority (90 to 95 percent) of ALS cases occur sporadically with no identifiable cause (sporadic ALS). However, 5 to 10 percent of ALS patients have a family history of the disease (familial myotrophic lateral sclerosis). In these cases, it is thought that the disease is the result of a genetic mutation that has an autosomal dominant inheritance pattern. This means that only one parent must carry the mutated gene for it to be passed to future generations. Sporadic ALS and familial ALS have identical symptoms, patterns of progression and prognosis.

A type of amyotrophic lateral sclerosis, called Guamanian ALS, was observed in Guam and elsewhere in the Pacific during the 1950s. However, this form of ALS is now rare. Many of these cases were also associated with other neurological disorders, such as Parkinson's disease and Alzheimer's disease.

ALS can be confused with other conditions that have similar symptoms, such as Parkinson's disease, Lyme disease and stroke. However, an important distinction between ALS and some other motor disorders is that ALS rarely results in any decline of mental function. ALS patients also do not have the tremor that is characteristic of Parkinson's disease.

Potential causes of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) can develop in anyone. The symptoms of the disease are caused by the degradation of motor neurons, which are essential for muscle control and movement. What causes the neurons to degrade is unknown in the vast majority of cases.

A genetic mutation has been identified in 20 percent of patients with familial ALS (which equates to one or two percent of all ALS patients). The mutation affects the body's ability to produce the antioxidant SOD1 (superoxide dismutase 1). Without this antioxidant, harmful free radical chemicals collect in the body and may cause the degeneration of motor neurons.

Patients with the SOD1 mutation have the ability to pass the mutation to any offspring they may have. ALS is typically inherited in an autosomal dominant pattern, which means that only one parent must have the mutation for it to be passed onto the next generation. There is a 50 percent chance that the offspring of people with this genetic mutation will develop the disease based on the typical autosomal dominant inheritance pattern, although there can be some variability in individual cases.

Researchers continue to search for other causes of both familial and sporadic amyotrophic lateral sclerosis. Possibilities include:

• Glutamate. This chemical is a neurotransmitter that is usually involved in transferring signals between neurons. Excessive amounts of glutamate can cause neurons to die. ALS patients frequently have higher than normal levels.
• Neurofilament arrangement. Neurofilaments are structural units of neurons that help maintain cell shape and are involved in nerve signal transmission. The misarrangment of neurofilaments can prevent nerve cells from signaling muscles and eventually lead to neuron death. Some ALS patients have a genetic mutation that may disrupt the proper arrangement of neurofilaments.
• Autoimmune disorders. These are conditions in which the immune system attacks the body's own cells. Some scientists suspect that certain types of autoimmune disorders may attack and kill neurons, resulting in the development of ALS.
• Others. Viral infections, trauma and exposure to toxins are among other possible causes of ALS that have been suggested by scientists. Research continues into whether these are potential causes of the disease.

Diagnosis methods for ALS

Amyotrophic lateral sclerosis (ALS) is typically diagnosed on the basis of signs and symptoms of progressive muscular weakness. Physical and neurological examinations are conducted to test muscle strength and reflexes. These examinations can also detect additional signs of disease, such as muscle twitching and atrophy. A family history of the disease is likely to confirm familial ALS.

The physician is likely to conduct other diagnostic tests to rule out other possible causes of muscle weakness and other signs and symptoms of the disease. When ALS is suspected, these tests may need to be repeated over time to monitor the progression of muscle weakness. Tests used to diagnose ALS include:

• Electromyogram (EMG). The electrical activity of muscles can be measured by inserting an electrode through the skin and into the target tissue. Results from repeated testing may be compared over months to monitor progressive loss of nerve signal strength.
• Nerve conduction velocity (NCV) studies. Another method of studying how signals are transmitted through nerves. A mild electric shock is sent from one electrode to another through a nerve. The speed that the signal travels between the two electrodes is called the nerve conduction velocity. Over time the signal will get weaker and move more slowly in ALS patients, reflecting the breakdown of neurons.
• Blood tests, urine tests and spinal tap tests. Fluids may be tested to exclude other possible causes of muscle weakness, such as Lyme disease.
• Imaging tests. MRIs (magnetic resonance imaging) and x-rays may be used to scan the body for other possible causes of muscle weakness. Brain scans can show changes in neural tissue that sometimes accompany ALS.
• DNA test. Blood samples can be tested for a genetic mutation that is found in approximately two percent of ALS patients. This is seldom used as a diagnostic tool and is usually only conducted on symptomatic patients who have a family history of the SOD1 genetic mutation.

Treatment of Amyotrophic Lateral Sclerosis (ALS)

There is no cure for amyotrophic lateral sclerosis (ALS), nor is there a method of preventing its development. Treatment is palliative in nature, thus focusing on helping the patient maintain as much mobility as possible and prolonging the patient's life.

Excessive amounts of the neurotransmitter glutamate are believed to cause neurons to die. An antiglutamate medication (riluzole) reduces the amount of this neurotransmitter in the body. It has been shown to slow the progression of the disease and extend the life of ALS patients by at least a few months. Side effects of the medication include weakness, dizziness, gastrointestinal disorders and changes in liver function.

Surgical procedures to ease breathing problems are sometimes performed in the latter stages of the disease. During a tracheostomy, a hole is made in the trachea (windpipe) and a tube is inserted. This bypasses many of the muscles involved in breathing and allows air to more easily reach the lungs.

Other forms of ALS treatment provide supportive care to ease the symptoms of patients. These might include:

• Physical therapy. This is designed to improve movement and muscle control in patients. Other types of therapy that may be useful include occupational therapy (to improve fine motor skills, such as the ability to tie shoelaces or button clothes), speech therapy and nutrition therapy.
• Mechanical respiratory assistance (breathing using a ventilator). This is usually used in the latter stages of the disease when the muscles that control breathing start to weaken significantly. It reduces the risk of death due to respiratory failure and aspiration pneumonia (pneumonia caused by the inhalation of foreign particles).
• Medications. There are several medication available that can reduce fatigue, muscle cramps, pain and other symptoms of amyotrophic lateral sclerosis.
• Counseling and other forms of support. Depression, anxiety and fear are common emotions for people who have been diagnosed with ALS. Individual or group counseling may be a valuable outlet for both patients and caregivers.
• Assistive devices. These may include canes, orthotics, higher toilet seats and specialized utensils. Eventually, most ALS patients will require a wheelchair.
• Caregiver assistance. In the latter stages of the disease, most patients require assistance with daily activities such as dressing, washing and buttoning clothes. In some cases, this may involve round-the-clock assistance in a nursing home.

Amyotrophic lateral sclerosis may develop in any person and there is no way to prevent the disease. Sometimes, patients with ALS experience a remission or halting of disease progression, but the mechanisms behind this occurrence are not understood.

DNA tests may confirm the presence of the genetic mutation that causes approximately 2 percent of cases. However, in the vast majority of cases, there is no way to predict the occurrence of the disease.

Adults with a family history of the disease may wish to undergo genetic counseling before having a child. Genetic counseling can help a person or couple learn more about the likelihood of passing genetic disorders to future generations, which can provide guidance for family planning.

Risk increases with

• Age over 40.
• Family history of ALS.
• Incidence is highest among those whose occupation demands strenuous physical labor.

Expected outcomes

Death usually occurs within two to seven years from the onset of symptoms. However, exceptions do occur. Some people have lived more than twenty years after diagnosis.

Possible complications

As the disease progresses, the individual becomes unable to speak, swallow, or move. The muscles used in respiration usually become affected making breathing difficult. Resulting complications may include choking, pressure sores, and respiratory complications. Swallowing dysfunction may cause pneumonia.

Medications

• There are no medications to treat ALS.
• Antibiotics to fight infection if pneumonia develops.
• Baclofen may help reduce spasticity.
• Antidepressant may help to decrease saliva production.

Valium (Diazepam)

Activity

• Stay as active as possible. Weakness will gradually limit capability. A rehabilitation program can help in maintaining independence as long as possible.
• Obtain equipment that will aid in mobility, such as walker or wheelchair.

Diet

• If swallowing is difficult, soft, easy-to-swallow foods.
• May require tube feedings eventually.

Appropriate specialists

Neurologist, physical therapist and occupational therapist.

Last updated 25 June 2015