Amyotrophic Lateral Sclerosis – Causes, Signs and symptoms

Amyotrophic Lateral Sclerosis

Also called: ALS, Lou Gehrig’s Disease

Summary

Amyotrophic lateral sclerosis (ALS) is a neurological condition that causes gradual loss of mobility in affected patients. ALS is also known as Lou Gehrig’s disease, named after the famous baseball player who died from the disease in 1941. Patients with ALS typically die from respiratory failure within three to five years of diagnosis.

ALS is characterized by the degradation and eventual death of motor neurons. These nerve cells transmit signals from the brain to the muscles involved in movement. Without the nerve signals, the muscles stop functioning and begin to waste away (atrophy). A patient is likely to experience muscle weakness that gradually progresses to complete loss of movement (paralysis). Most patients experience the first symptoms after the age of 40.

Anyone can develop ALS, but it is a rare condition. Fewer than 6,000 cases are diagnosed each year in the United States, according to the ALS Association.

The cause of most cases of ALS is unknown. Between 90 and 95 percent of patients have no family history of the disease. Of the remaining patients with ALS, approximately 20 percent of cases have been linked to a mutation in the SOD1 gene. It is thought that this mutation affects the way in which certain harmful elements are processed in the body, causing them to build up and consequently damage motor neurons. The disease may also be related to glutamate, a neurotransmitter that has been found in high levels in ALS patients.

ALS progresses slowly and its symptoms may not be noticed for some time. Symptoms are likely to include muscle weakness or twitching, slurred and/or nasal speech, and difficulty with chewing and swallowing. Patients are likely to trip more often and lose strength in their hands, which can affect fine motor skills, such as buttoning clothes and other such activities of daily living.

The diagnosis of ALS is usually based on the presence of symptoms. A family history of the disease accompanied by signs and symptoms is a strong indication of ALS. A physician may perform tests to exclude other possible causes of muscle weakness. These tests may include electromyography (EMG), nerve conduction velocity (NCV) studies and magnetic resonance imaging (MRI). Some tests may be repeated over time to monitor disease is progression. There is no cure for ALS. Medications have been developed to reduce the levels of glutamate in the body and they have been shown to extend the lives of ALS patients for a few months. Other measures are available to improve the patient’s mobility and reduce the severity of symptoms. ALS is typically fatal and respiratory failure is the leading cause of death in affected individuals.

About 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 ALS). 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 ALS, 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 ALS. 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.

Signs and symptoms of ALS

Amyotrophic lateral sclerosis (ALS) is a progressive disease, which means that the signs and symptoms of grow more severe as the disease advances. The first indication of ALS is usually muscle weakness or twitching. These symptoms are usually mild when they first occur and are often overlooked by patients and caregivers. They can also be mistaken for other disorders, such as Parkinson’s disease or stroke. In the case of late-onset ALS, early symptoms can be confused with the natural signs of aging.

The early symptoms typically start in one hand or in the facial muscles before moving to other parts of the body. Other early symptoms include:

  • Slurred or nasal speech or difficulty in projecting voice
  • Frequent tripping or dropping things
  • Muscle cramps, spasms or twitching (fasciculation)
  • Loss of muscle bulk
  • Uncontrollable laughing, crying or yawning

The symptoms and progression of ALS may vary widely between patients. Most (60 percent) will experience muscle weakness as these tissues atrophy. Some patients experience pain from muscle spasms. Other late-stage symptoms include:

  • Shortness of breath
  • Drooling
  • Difficulty lifting or holding up the head
  • Constipation

As the muscles continue to degrade, patients lose their mobility and become paralyzed. Eventually, the muscles involved in swallowing and breathing weaken, which usually results in death from respiratory failure.

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 and prevention of 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 ALS.

  • 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.

ALS 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.

Questions for your doctor regarding ALS

Preparing questions in advance can help patients to have more meaningful discussions with healthcare professionals regarding their condition. Patients may wish to ask their doctor the following questions related to amyotrophic lateral sclerosis (ALS):

  1. What do you think caused my ALS?
  2. What is my prognosis?
  3. Is there treatment for my ALS?
  4. If a family member has had ALS, am I or my children at greater risk for the disease?
  5. What symptoms may indicate the start of ALS?
  6. Will my mental ability by affected?
  7. How often should I be tested for signs that the disease is progressing?
  8. Is there anyway to prevent my ALS from getting worse?
  9. What does a diagnosis of ALS mean for me and my family?
  10. Can you recommend a counselor to help me and my family cope with ALS?
  11. Are there new medications or treatment options available that might help?
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