What is ALS?
Amyotrophic lateral sclerosis (ALS), often referred to as “Lou Gehrig’s Disease,” is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
A-myo-trophic comes from the Greek language. “A” means no or negative. “Myo” refers to muscle, and “Trophic” means nourishment–”No muscle nourishment.” When a muscle has no nourishment, it “atrophies” or wastes away. “Lateral” identifies the areas in a person’s spinal cord where portions of the nerve cells that signal and control the muscles are located. As this area degenerates it leads to scarring or hardening (“sclerosis”) in the region.
As motor neurons degenerate, they can no longer send impulses to the muscle fibers that normally result in muscle movement. Early symptoms of ALS often include increasing muscle weakness, especially involving the arms and legs, speech, swallowing or breathing. When muscles no longer receive the messages from the motor neurons that they require to function, the muscles begin to atrophy (become smaller). Limbs begin to look “thinner” as muscle tissue atrophies.
What Types of Nerves Make Your Body Work Properly?
(from Living with ALS, Manual 1: What’s It All About?)
The body has many kinds of nerves. There are those involved in the process of thinking, memory, and of detecting sensations (such as hot/cold, sharp/dull), and others for vision, hearing, and other bodily functions. The nerves that are affected when you have ALS are the motor neurons that provide voluntary movements andmuscle power. Examples of voluntary movements are your making the effort to reach for the phone or step off a curb; these actions are controlled by the muscles in the arms and legs.
The heart and the digestive system are also made of muscle but a different kind, and their movements are not under voluntary control. When your heart beats or a meal is digested, it all happens automatically. Therefore, the heart and digestive system are not involved in ALS. Breathing also may seem to be involuntary. Remember, though, while you cannot stop your heart, you can hold your breath – so be aware that ALS may eventually have an impact on breathing.
Although the cause of ALS is not completely understood, the recent years have brought a wealth of new scientific understanding regarding the physiology of this disease.
While there is not a cure or treatment today that halts or reverses ALS, there is one FDA approved drug, riluzole, that modestly slows the progression of ALS as well as several other drugs in clinical trials that hold promise.
Importantly, there are significant devices and therapies that can manage the symptoms of ALS that help people maintain as much independence as possible and prolong survival. It is important to remember that ALS is a quite variable disease; no two people will have the same journey or experiences. There are medically documented cases of people in whom ALS ‘burns out,’ stops progressing or progresses at a very slow rate. No matter what your individual course or situation may be, The ALS Association and your medical team are here to help.
To learn more about the personal stories of people who are living fully, click here. As one man put it, “I’ve made ALS part of my life, not my whole life.”
Facts You Should Know
- ALS is not contagious.
- It is estimated that ALS is responsible for nearly two deaths per hundred thousand population annually.
- Approximately 5,600 people in the U.S. are diagnosed with ALS each year. The incidence of ALS is two per 100,000 people, and it is estimated that as many as 30,000 Americans may have the disease at any given time.
- Although the life expectancy of an ALS patient averages about two to five years from the time of diagnosis, this disease is variable and many people live with quality for five years and more. More than half of all patients live more than three years after diagnosis.
- About twenty percent of people with ALS live five years or more and up to ten percent will survive more than ten years and five percent will live 20 years. There are people in whom ALS has stopped progressing and a small number of people in whom the symptoms of ALS reversed.
- ALS occurs throughout the world with no racial, ethnic or socioeconomic boundaries.
- ALS can strike anyone.
- The onset of ALS is insidious with muscle weakness or stiffness as early symptoms. Progression of weakness, wasting and paralysis of the muscles of the limbs and trunk as well as those that control vital functions such as speech, swallowing and later breathing generally follows.
- There can be significant costs for medical care, equipment and home health caregiving later in the disease. It is important to be knowledgeable about your health plan coverage and other programs for which your may be eligible, including SSA, Medicare, Medical and Veteran Affairs benefits.
- Riluzole, the first treatment to alter the course of ALS, was approved by the FDA in late 1995. This antiglutamate drug was shown scientifically to prolong the life of persons with ALS by at least a few months. More recent studies suggest Riluzole slows the progress of ALS, allowing the patient more time in the higher functioning states when their function is less affected by ALS. Click here for more information on the drug. Many private health plans cover the cost of Riluzole. Further information on Riluzole coverage through Medicare Prescription Drug Benefit can be found in the Advocacy pages of this website.
Reports from three separate patient databases described long range experience with Riluzole. All three reports suggest a trend of increasing survival with Riluzole over time. More studies that are double blind and controlled are needed to confirm these database observations. The trend appears to indicate that longer periods of time than those used in the Riluzole clinical trials may be needed to see the long-term survival advantage of the drug. An interesting observation was that despite the fact that the Irish government provides Riluzole free of charge to people in Ireland with ALS, only two-thirds of the patients registered in the Ireland national ALS database reported taking Riluzole.
Who Gets ALS?
ALS is a disorder that affects the function of nerves and muscles. Based on U.S. population studies, a little over 5,600 people in the U.S. are diagnosed with ALS each year. (That’s 15 new cases a day.) It is estimated that as many as 30,000 Americans have the disease at any given time. According to the ALS CARE Database, 60% of the people with ALS in the Database are men and 93% of patients in the Database are Caucasian.
Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. However, cases of the disease do occur in persons in their twenties and thirties. Generally though, ALS occurs in greater percentages as men and women grow older. ALS is 20% more common in men than in women. However with increasing age, the incidence of ALS is more equal between men and women.
There are several research studies – past and present – investigating possible risk factors that may be associated with ALS. More work is needed to conclusively determine what genetics and/or environment factors contribute to developing ALS. It is known, however, that military veterans, particularly those deployed during the Gulf War, are approximately twice as likely to develop ALS.
Half of all people affected with ALS live at least three or more years after diagnosis. Twenty percent live five years or more; up to ten percent will live more than ten years.
There is some evidence that people with ALS are living longer, at least partially due to clinical management interventions, riluzole and possibly other compounds and drugs under investigation.
Last revised 2/2011
ALS is a very difficult disease to diagnose. To date, there is no one test or procedure to ultimately establish the diagnosis of ALS. It is through a clinical examination and series of diagnostic tests, often ruling out other diseases that mimic ALS, that a diagnosis can be established. A comprehensive diagnostic workup includes most, if not all, of the following procedures:
- electrodiagnostic tests including electomyography (EMG) and nerve conduction velocity (NCV)
- blood and urine studies including high resolution serum protein electrophoresis, thyroid and parathyroid hormone levels and 24-hour urine collection for heavy metals
- spinal tap
- x-rays, including magnetic resonance imaging (MRI)
- myelogram of cervical spine
- muscle and/or nerve biopsy
- thorough neurological examination
For more information on the importance of a second opinion, click here.
These tests are done at the discretion of the physician, usually based on the results of other diagnostic tests and the physical examination. There are several diseases that have some of the same symptoms as ALS and most of these conditions are treatable. It is for this reason that The ALS Association recommends that a person diagnosed with ALS seek a second opinion from an ALS “expert” – someone who diagnoses and treats many ALS patients and has training in this medial specialty. The ALS Association maintains a list of recognized experts in the field of ALS. See ALS Association Certified Centers of ExcellenceSM, ALS Clinics and contact your local ALS Association Chapter or the National Office.
Initial Symptoms of the Disease
At the onset of ALS the symptoms may be so slight that they are frequently overlooked. With regard to the appearance of symptoms and the progression of the illness, the course of the disease may include the following:
- muscle weakness in one or more of the following: hands, arms, legs or the muscles of speech,
swallowing or breathing
- twitching (fasciculation) and cramping of muscles, especially those in the hands and feet
- impairment of the use of the arms and legs
- “thick speech” and difficulty in projecting the voice
- in more advanced stages, shortness of breath, difficulty in breathing and swallowing
The initial symptoms of ALS can be quite varied in different people. One person may experience tripping over carpet edges, another person may have trouble lifting and a third person’s early symptom may be slurred speech. The rate at which ALS progresses can be quite variable from one person to another. Although the mean survival time with ALS is three to five years, many people live five, ten or more years. In a small number of people, ALS is known to remit or halt its progression, though there is no scientific understanding as to how and why this happens. Symptoms can begin in the muscles of speech, swallowing or in the hands, arms, legs or feet. Not all people with ALS experience the same symptoms or the same sequences or patterns of progression. But, progressive muscle weakness and paralysis are universally experienced.
Muscle weakness is a hallmark initial sign in ALS, occurring in approximately 60% of patients. Early symptoms vary with each individual, but usually include tripping, dropping things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and twitches and/or uncontrollable periods of laughing or crying.
The hands and feet may be affected first, causing difficulty in lifting, walking or using the hands for the activities of daily living such as dressing, washing and buttoning clothes.
As the weakening and paralysis continue to spread to the muscles of the trunk of the body the disease, eventually affects speech, swallowing, chewing and breathing. When the breathing muscles become affected, ultimately, the patient will need permanent ventilatory support in order to survive.
Since ALS attacks only motor neurons, the sense of sight, touch, hearing, taste and smell are not affected. For many people, muscles of the eyes and bladder are generally not affected.
Forms of ALS
Three classifications of ALS have been described:
Sporadic – the most common form of ALS in the United States – 90 to 95% of all cases.
- Familial – occurring more than once in a family lineage (genetic dominant inheritance) accounts for a very small number of cases in the United States – 5 to 10% of all cases.
- Guamanian – an extremely high incidence of ALS was observed in Guam and the Trust Territories of the Pacific in the 1950’s.
The most common form of ALS in the United States is “sporadic” ALS. It may affect anyone, anywhere. “Familial” ALS (FALS) means the disease is inherited. Only about 5 to 10% of all ALS patients appear to have genetic or inherited form of ALS. In those families, there is a 50% chance each offspring will inherit the gene mutation and may develop the disease.
Genetic Testing for ALS
Is ALS hereditary?
ALS is directly hereditary in only a small percentage of families. About 90% of patients with adult-onset ALS have no family history of ALS and present as an isolated case in their family. This is called sporadic ALS (SALS), and although there is likely a genetic predisposition involved, SALS is not directly inherited. Rarely, a person may initially appear to be affected with sporadic disease, but only because the family history isn’t known or is limited. This can happen when an individual is adopted or if the individual’s parents died at a young age. The remaining 10% of people with ALS have a family member with ALS, and this is referred to as familial ALS (FALS).
Currently the best tool to distinguish between SALS and FALS is the family history. A neurologist or genetic counselor will ask whether anyone else has ever been diagnosed with ALS, and if anyone else in the family had progressive walking or speech problems. If so, they will likely ask additional questions to see if the health problems were related to ALS or another cause. They will also inquire about the ages that family members passed away to see if any close relatives passed away at a young age, meaning that a long health history is not available. It’s very common to have limited information on one’s family, but most families can still be reassured as the majority of instances of ALS are not hereditary. Older relatives are often good sources of family history information, and medical records can often be obtained with the help of a hospital’s medical release form.
How is FALS inherited?
To answer this question, it’s helpful to review some basic information on genetics. Every cell in the human body contains genes. Genes have many functions, and act as an ‘instruction manual’ for our cells. Some genes contribute to traits like eye and hair color while other genes are responsible for making proteins that determine how our bodies circulate blood or send nerve signals to muscles. When a gene is disrupted by a change in its sequence called a mutation, the gene cannot function correctly.
Genes are packaged in chromosomes, and chromosomes are present in pairs. Our genes, therefore, are also present in pairs. For each chromosome pair, one is inherited from the mother and one is inherited from the father. We have 23 pairs of chromosomes, giving us a total of 46 chromosomes. The first 22 pairs are the autosomes, and both males and females share them in common. Only the 23rd pair differs between males and females – these are the sex chromosomes, and females typically have two Xs and males have an X and a Y.
There are several inheritance patterns, but the most common inheritance pattern for FALS is called autosomal dominant. Autosomal means that it is equally likely that a female or male would inherit the gene mutation for FALS because the gene is located on an autosome – a chromosome that both males and females share in common. Dominant refers to the fact that a person only needs one gene to have a mutation in a gene for FALS to have an increased risk for ALS. Someone who has FALS would have one copy of the gene with a mutation and one copy of the gene without a mutation. Therefore, a child born to someone who has FALS has a 50% chance to inherit the FALS gene mutation and conversely, a 50% chance to not inherit the FALS gene mutation. This 1 in 2, or 50% chance, comes from the fact that parents randomly pass on only one member of their gene pair, so that either the gene with the mutation will be passed on or the gene without the mutation will be passed on. Even though parents often feel responsible for their children’s health, they have no control over which gene they pass on, just as their parent had no control which gene they passed onto their child. It is also important to remember that inheriting the gene for FALS in no way guarantees that a person will develop symptoms of ALS. Also, if a child does not inherit the gene mutation for ALS, they cannot pass it onto their children.
Is there a genetic test for FALS?
Yes, although genetic testing is limited. About 50% of families with FALS will have a mutation found in one of the genes known to be associated with ALS. The remaining 50% of families with FALS will have normal genetic testing results – presumably because they have mutations in genes we have not identified yet and therefore cannot test.
The most common genes currently known to be associated with FALS include SOD1, TDP-43, FUS and the more recently discovered C9ORF72 and UBQLN2. A neurologist familiar with FALS and a genetic counselor may decide to test affected family members for one or several of these genes based on that individual’s neurological exam and specific family history.
Prenatal genetic testing technology for FALS mutations exist when there is a known mutation within the family. Patients and their families should discuss questions and concerns with their neurologist and genetic counselor for more information about this complex and personal matter.
For families that do not have a change in any of the currently known FALS genes, a normal genetic test is not informative. Unaffected family members cannot pursue presymptomatic testing to determine whether or not they carry the FALS mutation, because it is unidentified in their family. Although researchers are diligently looking for other genes, at this time there is no genetic testing to offer these families. Participation in ongoing research studies to identify new genetic factors is a way for families to help researchers identify more genes. For these reasons, the determination that an individual has FALS is typically based on family history rather than a genetic test.
Does a genetic test diagnose ALS?
No. Since the vast majority of patients do not have the hereditary type of ALS, a diagnosis of ALS is not determined by a genetic test. Instead, a neurologist makes the diagnosis after a review of a person’s symptoms, a neurological exam, and results on nerve and muscle function tests. Clinically, FALS and SALS are basically identical.
Who is appropriate for genetic testing?
Genetic testing is appropriate for anyone who has symptoms of ALS in addition to a family history of ALS, such as a parent, grandparent, aunt, uncle or sibling. Additionally, if one’s family history is unknown or a parent passed away at a young age, testing may also be appropriate. However, only about 5% of all patients with ALS will have a genetic change. Those patients with ALS without a family history can also be offered genetic testing but it is extremely important that it is offered in the context of genetic counseling or discussion with a neurologist about the implication of finding a mutation, as a mutation would mean that what was thought to be SALS is actually FALS. This is a rare situation.
What would the results of the genetic test tell me?
A positive test means that the genetic cause of FALS has been identified. A positive test does not change medical treatment at this time. Researchers have developed mouse models with similar genetic change so that they can better understand how changes in FALS genes can lead to the symptoms of ALS. Currently, new therapies are being tried on this animal model to slow or halt the progression of ALS. Although still in the distant future, gene therapy to correct the genetic change is also being researched. A positive test may or may not provide prognostic information, as particular mutations may affect the course of the disease. Even though the inheritance may already be established by the family history, an individual may feel furthered burdened by learning they carry a genetic change as concerns for children resurface. Others prefer to have this knowledge and may feel comforted that there is much research aimed specifically at ALS caused by changes in the FALS genes.
A negative test for an affected family member means only that the genetic cause of ALS has not been identified. However, this does not rule out familial ALS since there are still other unidentified genes that cause ALS in half of FALS families.
If I have a family history of FALS, should I have a genetic test even if I don’t have symptoms?
This situation is called presymptomatic testing. The decision to have presymptomatic genetic testing is highly personalized and often individuals in the same family will disagree whether to pursue it. However, in order for the test to be meaningful, a genetic change in a FALS gene needs to first be found in a family member affected with ALS. When a genetic change is not identified in a symptomatic person, presymptomatic genetic testing is not available for other family members, because the ALS is being caused by an unidentified gene, and therefore we cannot test for it.
Benefits of presymptomatic genetic testing in ALS are limited by the absence of preventative treatment and the inability to predict the age at which someone who is a gene carrier will get ALS or even that a gene carrier will definitely get ALS. Since both a negative or positive presymptomatic test result in a family with a known mutation can have a great emotional impact, genetic and psychological counseling is required before undergoing such testing. Individuals often consider how the information that they did or did not inherit the predisposing gene would affect their lives, who they would tell about the results, and how relationships may change depending on the results.
Individuals who learn they do not carry the family’s genetic change often feel great relief, although they can sometimes wonder why they escaped while another family member did not. They may regret past decisions made based on the presumed at risk status, or find it hard to let go of that part of their identity. Learning that one does carry a predisposing gene is usually more difficult and that person may need ongoing professional support. Ambiguity is not entirely erased as the question may change from ‘Do I carry the gene?’ to ‘When or will I get symptoms?’ Commitment to friends and family may be strengthened. A genetic counselor can further discuss the issues involved in presymptomatic testing including insurance and employment discrimination concerns.
How is the genetic test done?
A blood sample is taken and sent to a specialized lab where the genetic material, or DNA, is removed. Special laboratory techniques allow the genes of interest to be replicated and then tested. One form of testing is running the sample on a gel to generate a series of bands. If a genetic change is present, the bands will be in a different location compared to a control sample, which is known not to have a genetic change in the gene. This method is called single strand conformation polymorphism – SSCP for short. Another method called sequencing may also be used to either initially test or confirm results. Sequencing is able to view the DNA on a finer scale by displaying the actual letters of the ‘instruction book’ so that changes can be seen.
How long does the genetic test take?
This varies depending on the genes being tested and the laboratory doing the testing. On average, the test usually takes about two to three months. The cost varies as well, from about $300-500 up to $4,000 for a panel (multiple gene tests done at one time).
The ALS Association:
Established in 1985, The ALS Association is the only national non-profit organization fighting Lou Gehrig’s Disease on every front. By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure.
As the preeminent ALS organization, The Association leads the way in research, care services, public education, and public policy — giving help and hope to those facing the disease. The Association’s nationwide network of chapters provides comprehensive patient services and support to the ALS community. The mission of The ALS Association is to lead the fight to treat and cure ALS through global research and nationwide advocacy, while also empowering people with Lou Gehrig’s Disease and their families to live fuller lives by providing them with compassionate care and support.