We all deserve a lifetime to achieve our hopes and dreams. For our friends with ALS, a lifetime is often shortened to three to five years after diagnosis. ALS (also known as amyotrophic lateral sclerosis or Lou Gehrig’s disease) steals the ability to walk, stand, hug, move, talk and even breathe. This debilitating disease takes away people’s everyday freedoms. MDA is fighting to give those freedoms back — to give people a lifetime to share their talents, accomplish their dreams and have more time with the people they love.
Thanks to the ALS Ice Bucket Challenge that swept our nation in 2014, more people than ever before know about ALS. MDA is grateful to everyone who participated in this challenge and took the first step, but we can’t stop there. ALS is a 365/24/7 fight.
Tens of thousands of people are currently fighting ALS. They are our wives, husbands, siblings, children and neighbors. They are fighting for...
Together, we can create a lifetime of these moments for Keith, Rick, Erin, Kristin, Patty, Joan, Richard and all the people living with ALS. With your support, we will fund doctors and scientists who are researching what causes ALS and find effective treatments and cures. Our collective strength will support more families living with ALS through MDA’s specialized clinics, support groups, education and equipment. But we need your help now to turn a wish for one more experience into a lifetime of fulfillment for people with ALS.
MDA's ALS Division is pleased to offer information about Eleanor Gehrig's connection to MDA, as well as a brief account of Lou Gehrig's experience with ALS, in the video "With Hope and Courage: Your Guide to Living with ALS."
Some 80 years ago, a muscular kid from a working class neighborhood in New York dove into the choppy waters of the Hudson River and swam all the way across to New Jersey. As a reward, the foolhardy youngster got his ears boxed by his father. The kid was Lou Gehrig.
Today, just a few streets away at Columbia Presbyterian Medical Center, Gehrig's name and that of his wife are enshrined at The Eleanor and Lou Gehrig MDA/ALS Center, one of some 40 MDA centers dedicated to ALS research and care.
Everyone knows that Lou, the great "Iron Horse" of baseball, had ALS. But why was his wife's name placed in honor above his? The answer is part of MDA history.
After Gehrig learned he had ALS and retired from the New York Yankees in 1939, ending his record streak of 2,130 consecutive games played, Eleanor was his chauffeur, nurse, nutritionist and constant companion. She exercised with him, steadied his fingers when he signed his name, and helped him take his daily injections of vitamin E.
So high was the Gehrigs' faith in vitamin E that Eleanor used to prepare a special salad for Lou made with common garden grass that she cut from the park because she was told it was rich with the vitamin. Even with salad dressing, the concoction made Gehrig gag. It didn't stop the progression, and in 1941, Lou Gehrig lost his life to ALS.
"After what happened to Lou, I was heartsick and wanted somehow to strike back," Eleanor said years later. "I felt that Lou would have wanted me to help others. But I realized that medical science hadn't really made a start in studying disorders of the neuromuscular system. Medical men generally deemed such diseases incurable."
In the early 1950s, Eleanor heard that a new organization called the Muscular Dystrophy Association was being formed to combat neuromuscular diseases. "I saw that here was the answer to my personal need — people whose thirst for action was as deep as my own. I immediately offered my services."
With Eleanor's help, MDA was to become and remain the world's leading private research organization and service provider for those with ALS.
Eleanor served as MDA's national campaign chairman during crucial formative years in the 1950s and 1960s. The late Robert Ross, former MDA president and CEO, accompanied her as she traveled the country giving speeches and interviews, and telling people like first lady Mamie Eisenhower about the agency's mission.
Eleanor assisted in chapter development, recruited volunteers — including many celebrities —and persuaded radio and television program sponsors to give free publicity to MDA's annual fundraising campaign. She was an MDA corporate member from 1955 through 1964.
In her later years, Eleanor had many friends, including the late wife of MDA Chairman of the Board R. Rodney Howell, M.D., Sarah E. Howell. Sarah, a doctor herself, had an abiding connection to the Gehrigs. Her father, Dr. Caldwell Esselstyn, had been Lou's personal physician during his years fighting ALS.
Sarah, only weeks before her death in 1993, placed the inscription shown below in a copy she gave to MDA's Ross of a Lou Gehrig biography co-authored by Mrs. Gehrig. The insertion describes Sarah's vivid childhood memory of seeing the Iron Horse in the flesh:
ALS is a disease of the parts of the nervous system that control voluntary muscle movement. In ALS, motor neurons (nerve cells that control muscle cells) are gradually lost. As these motor neurons are lost, the muscles they control become weak and then nonfunctional.
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.
In the United States, ALS also is called Lou Gehrig’s disease, named after the Yankees baseball player who died of it in 1941. In the United Kingdom and some other parts of the world, ALS is often called motor neurone disease in reference to the cells that are lost in this disorder.
ALS usually strikes in late middle age (the late 50s is average) or later, although it also occurs in young adults and even in children, as well as in very elderly people. Some forms of ALS have their onset in youth. Men are slightly more likely to develop ALS than are women. Studies suggest an overall ratio of about 1.2 men to every woman who develops the disorder.
Years ago, it was widely believed that there might be one cause to explain all cases of ALS. Today, doctors and scientists know that can’t be the case, and they’re working to identify the multiple causes of the disorder. One thing they do know is that ALS cannot be "caught," or transmitted from one person to another.
The causes of the vast majority of ALS cases are still unknown. Investigators theorize that some individuals may be genetically predisposed to developing the disease, but only do so after coming in contact with an environmental trigger. The interaction of genetics and environment may hold clues as to why some individuals develop ALS.
Although the majority of ALS cases are sporadic, meaning there is no family history of the disease, about 5 to 10 percent of cases are familial, meaning the disease runs in the family. A common misconception is that only familial ALS is "genetic." Actually, both familial and sporadic ALS can stem from genetic causes. And some people who have a diagnosis of sporadic ALS may carry ALS-causing genetic mutations that can be passed on to offspring. A genetic counselor can help people with ALS understand inheritance and any associated risks for family members.
For a more detailed discussion of possible causes of sporadic ALS and the genetics of familial ALS, please see Causes/Inheritance.
ALS results in muscles that are weak and soft, or stiff, tight and spastic. Muscle twitches and cramps are common; they occur because degenerating axons (long fibers extending from nerve-cell bodies) become “irritable.” Symptoms may be limited to a single body region, or mild symptoms may affect more than one region. When ALS begins in the bulbar motor neurons, the muscles used for swallowing and speaking are affected first. Rarely, symptoms begin in the respiratory muscles.
As ALS progresses, symptoms become more widespread, and some muscles become paralyzed while others are weakened or unaffected. In late-stage ALS, most voluntary muscles are paralyzed.
The involuntary muscles, such as those that control the heartbeat, gastrointestinal tract and bowel, bladder and sexual functions are not directly affected in ALS. Sensations, such as vision, hearing and touch, are also unaffected.
About 50 percent of people with ALS develop some degree of cognitive (thinking) or behavioral abnormality. Usually, cognitive and behavioral symptoms in ALS range from mild (such that only close family members may notice a difference) to moderate.
Each person's disease course is unique. There are a number of examples of people who are leading productive and active lives more than two decades after an ALS diagnosis.
Standard longevity statistics citing an average survival time of three to five years after diagnosis may be somewhat out of date because changes in supportive care and technology — especially for breathing and nutrition — may help prolong life.
For more information on the disease course, see Medical Management.
Medical interventions and technology have vastly improved the quality of life for people with ALS, by assisting with breathing, nutrition, mobility and communication. Proper management of symptoms, and proactive use of medical interventions and equipment, can make a positive difference in day-to-day living, and potentially may lengthen survival. The FDA-approved drug riluzole (brand name Rilutek) has been shown to slightly increase longevity.
A number of strategies and approaches are being tested around the world, both in the laboratory and in human clinical trials. MDA's basic science program is constantly pursuing new avenues of research to understand the underlying causes of ALS, with a sharp focus on developing treatments.
As of 2012, intense research is being conducted on genetic factors in ALS, the role of the immune system in ALS, and the role of cells other than nerve cells in this disease. In addition, many medications and other treatments are being tested for potential benefits in ALS. For details about current ALS research, go to Research and Clinical Trials.
|Upper motor neurons normally send signals to lower motor neurons, which send signals to muscles. In ALS, both upper and lower motor neurons are lost.|
ALS affects the upper motor neurons, which are in the brain, and the lower motor neurons, which are in the spinal cord and brainstem. Upper motor neuron degeneration generally causes spasticity (tightness in a muscle), while lower motor neuron degeneration causes muscle weakness, muscle atrophy (shrinkage of muscles) and twitching. These can occur in combination in ALS, as upper and lower motor neurons are being lost at the same time.
ALS can affect people of any age, though it usually strikes in late middle age. ALS usually announces itself with persistent weakness or spasticity in an arm or leg, causing difficulty using the affected limb. Sometimes the problem originates in the muscles controlling speech or swallowing. It isn’t unusual for people to ignore such problems for some time at this stage, or to consult a physician who may be relatively unconcerned.
However, the disease — if it’s truly ALS — generally spreads from one part of the body to another (almost always in parts adjacent to each other) so that eventually the problem can no longer be ignored.
It’s at this point that people usually are referred to a neurologist, who will consider ALS among many other possible diagnoses.
The involuntary muscles (such as those that control the heartbeat, gastrointestinal tract, bowel and bladder function) and sexual functions are not directly affected in ALS. However, prolonged inability to move and other effects of ALS can have an indirect impact. Hearing, vision and touch generally remain normal.
Nor is pain a direct consequence of ALS, although pain can occur as a result of immobility and its various complications, especially if precautions such as daily range-of-motion exercises are not undertaken.
Fasciculations are a common symptom of ALS. These persistent muscle twitches are generally not painful, but can be annoying or interfere with sleep. They are the result of the ongoing disruption of signals from the nerves to the muscles that occurs in ALS.
Some with ALS experience painful muscle cramps, which can sometimes be alleviated with medication.
About half of the people with ALS undergo alterations in their thinking or may exhibit uncharacteristic behavior changes, often referred to as frontotemporal dementia, or FTD. However memory loss, a hallmark of Alzheimer's-type dementia, is generally not a feature of most cognitive changes in ALS. Instead, the person with ALS might be irritable, inconsiderate, apathetic, ritualistic, impulsive or otherwise act in uncharacteristic ways.
Another potential ALS symptom — not experienced by all — is a temporary lapse of control over emotional expressions such as laughing or crying, a phenomenon called pseudobulbar affect. Laughing or crying bouts, often triggered by the smallest of things, are more related to the disease process rather than to actual feelings of happiness or sadness. Medications such as Nuedexta and various other strategies can help manage this symptom.
For more about the progression of ALS symptoms over the full course of the disease, see Stages of ALS.
For a more complete list of symptoms and daily care in ALS, see the MDA ALS Caregiver's Guide, Chapter 2.
At the End
There are some specific criteria for the diagnosis of ALS known as the El Escorial criteria. (They're named after a conference center in Spain, where they were developed in 1990.)
According to the El Escorial criteria, a diagnosis of ALS requires the following:
A thorough medical and family history and physical examination are the starting points of a neurologic work-up, which includes simple, in-office tests of muscle and nerve function.
If ALS is suspected, the next step is usually an electromyogram, or EMG. This test measures the signals that run between nerves and muscles and the electrical activity inside muscles to see if there’s a pattern consistent with ALS. If there is, more tests likely will be ordered.
Additional tests may include imaging of the spinal cord and brain, usually by MRI (magnetic resonance imaging), and sometimes a test of the fluid surrounding the spinal cord (spinal tap or lumbar puncture), which involves inserting a needle into the back between two lower vertebrae.
Blood tests to exclude disorders that mimic ALS are also performed. In some instances, a muscle biopsy, which involves taking a small sample of muscle under local anesthesia, is performed.
In some cases, genetic tests (performed on a blood sample) can confirm the diagnosis (see Causes/Inheritance).
However, the diagnosis of ALS is often a “rule-out” procedure. This means ALS is diagnosed after all other possibilities have been ruled out by specific tests.
Among the conditions that resemble ALS are some forms of muscular dystrophy, the neurologic conditions known as spinal-bulbar muscular atrophy and adult-onset spinal muscular atrophy, the nerve-to-muscle transmission disorder known as myasthenia gravis, and various causes of compression of the spinal cord or brainstem, such as tumors and malformations.
If your condition has been diagnosed as ALS outside a major medical center or without extensive testing, it may be worth getting a second opinion.
About 5 to 10 percent of ALS is familial — meaning it arises in families in which there is a history of ALS. Several genes associated with ALS have been identified or at least mapped to a specific region of a chromosome.
The other 90 to 95 percent of ALS is sporadic, meaning it occurs without a family history (in other words, "sporadically"). There appear to be genetic variations that influence one's susceptibility to sporadic ALS, even if they don't actually cause the disease by themselves.
Below you will find an examination of possible causes of both sporadic and familial ALS currently under investigation by MDA researchers:
Oxidative stress is a phenomenon that occurs when there's an imbalance between the production of oxygen-containing molecules that carry an electrical charge, which can be toxic, and a biological system's ability to readily detoxify them. Oxygen-containing, charged particles are common byproducts of cellular metabolism.
The mitochondria are microscopic energy "factories" inside cells. They resemble miniature cells themselves and have their own DNA. Abnormalities of the mitochondria may be involved in ALS causation and/or progression.
Abnormalities of the immune system
There is evidence that the immune system, particularly immunologic cells in the nervous system known as microglia, can be both beneficial and harmful in ALS. Microglia may be protective up to a certain point and then become damaging. Modifying the actions of the immune system is an active area of ALS research.
|Glutamate carries signals between neurons (nerve cells), and there may be too much of it in ALS.|
Glutamate is one of many neurotransmitter chemicals in the nervous system that carries signals between nerve cells. There is some evidence that in ALS glutamate accumulates in the spaces around a nerve cell after it has completed its signaling function, causing problems for the nerve cells in its vicinity. The problem could be caused by inadequate transport of glutamate away from the cells.
The only FDA-approved drug for ALS, riluzole (Rilutek), is based on reducing glutamate levels. Riluzole has a modest effect on slowing disease progression and prolonging survival.
There is some evidence that normally dormant viral DNA could be causing damage in ALS. Recent studies have suggested that a viral protein called HERV-K reverse transcriptase is much more prevalent in ALS-affected brain samples than it is in brain samples from people without ALS.
For years, experts have tried to find factors common to people who develop ALS, such as environmental toxins, occupational hazards, places of work or residence, exposure to chemicals and so forth. So far, the evidence for such risk factors and triggers has been frustratingly unclear, although a recent finding of an association between developing ALS and having served in the military is one of the strongest of these proposed risk factors.
In particular, the association of military service in the Gulf War with ALS may yield some clues. Environmental toxins, such as burning oil fires, may have contributed.
Cyanobacteria, microorganisms that live in desert sands and which can be inhaled when they're kicked up in dust, could be among the reasons for the elevated risk of ALS in those who served in the Gulf War, some experts believe.
Cyanobacteria are also found in some bodies of water. In 2009, some experts suggested water contamination of a lake in New Hampshire as a possible cause of an apparent increase in ALS risk in the surrounding area. However, the evidence for this link is not strong.
Higher-than-average rates of ALS on the island of Guam have led scientists to suspect a possible toxic factor may have been involved there, at least historically. Recent evidence suggests that inclusion in the native peoples' diet of poisonous nuts from the indigenous cycad trees could be an explanation.
The heavy metals lead, mercury and arsenic, although they can be toxic to the nervous system, haven't been shown to be causative agents in ALS.
Genetic influences on sporadic ALS
There are some variants of genes that may increase susceptibility to the development of ALS. These may work in concert with other factors.
The term "familial" ALS means that there is more than one occurrence of the disease in a family. The term "sporadic" applies when there is no known history of other family members with the disease. The term "genetic" can apply to both familial and sporadic ALS. In some sporadic cases, the family history may not be known. In others, parents may have died before showing signs of the disease. In still others, an ALS-causing genetic mutation may not have been present in either parent but may have occurred for the first time in the person with the disease. Once an ALS-causing mutation has occurred in someone, his or her children can inherit it, and their disease would be considered "familial."
Mutations in the SOD1 (superoxide dismutase 1) gene account for some 10 to 20 percent of familial ALS and also perhaps 1 to 3 percent of sporadic ALS. SOD1 was the first gene found to be associated with familial ALS, and a mouse model of SOD1-associated ALS is widely used in research today. Mutations in the SOD1 gene were identified as a cause of familial ALS in 1993. Since then, many more genes have been found that, when flawed, can cause familial ALS.
Mutations in the gene for the TDP43 protein have been found to be a cause of a small percentage of familial ALS. In 2009, scientists determined that mutations in the FUS gene also account for some cases of familial ALS.
In 2011, mutations in the gene for the ubiquilin 2 protein were identified as a cause of familial ALS. And at around the same time, a mutation in the C9ORF72 gene involving an expansion of repeated DNA sequences was found to account for more ALS cases than any previously identified genetic abnormality. Data from two independent research studies showed that the C9ORF72 mutation is more than twice as common as mutations in the SOD1 gene as a cause of familial ALS, and more than three times as common as mutations in TDP43, FUS and two other genes — optineurin and valosin-containing protein (VCP) gene — combined.
A database of genes that are or may be associated with ALS provides more information.
For more about inheritance patterns, see Facts About Genetics and Neuromuscular Diseases.
Genetic testing is available for many ALS-causing gene mutations. A genetic counselor can help interpret test results and discuss their implications for the person with ALS and his or her family.
To learn more about the causes of ALS, see Research.
Medical interventions and technology have vastly improved the quality of life for people with ALS by assisting with breathing, nutrition, mobility and communication. Proper management of symptoms, and proactive use of medical interventions and equipment can make a positive difference in day-to-day living, and potentially may lengthen survival.
Don't hesitate to discuss any medical or mental concern with your ALS doctor. "Beating" ALS means doing everything possible to cope with symptoms as they occur, if not before.
In October 2009, the American Academy of Neurology (AAN) released revised physician guidelines for medical management of ALS. To read them in summary and in full, see the ALS Care Guidelines. The guidelines include information about drug, nutritional and respiratory therapies, along with multidisciplinary care, symptom management and cognitive/behavioral impairment.
|Noninvasive ventilation can be provided via a nasal interface.|
The diaphragm is an arched muscle located just beneath the lungs, which moves up and down and allows air to come in and move out. The intercostals are muscles between the ribs that contract and relax and also assist with air movement. As the diaphragm and intercostal muscles weaken due to ALS, the act of breathing, which is entirely automatic for most people, becomes conscious and energy-consuming.
To preserve quality of life — and to prolong life itself in later stages of ALS — it will become necessary to introduce preventive measures. Such symptoms as the inability to cough, shortening of spoken sentences, daytime headaches and sleepiness, exhaustion and weight loss may indicate that breathing problems have advanced to the point where respiratory support will be valuable.
Shortly after an ALS diagnosis is made, many specialists recommend a breathing test called a forced vital capacity (FVC) and other pulmonary function tests (PFTs). These tests give the clinic team baseline measures against which later tests of breathing can be compared.
The physician may recommend noninvasive ventilation to compensate for weakened muscles by assisting the movement of air in and out of the lungs. Generally, supplemental oxygen is not prescribed for individuals with ALS unless there are other medical conditions that require it. It may even do harm, so it should be used with caution, if at all.
Noninvasive ventilation comes in many forms, but usually consists of two basic elements: an “interface,” such as a mask or nose inserts, and air delivered under pressure by a small, portable machine. Usually, there’s one pressure for inhalation and another pressure for exhalation. This type of machine is often called a BiPAP (a registered trademark of Philips Respironics) for bilevel positive airway pressure.
The device does not necessarily require around the clock use. Pressures, masks and other aspects of the device can be changed by the medical team as needed. Ideally, the person with ALS should try several interface options (full-face masks, nasal pillows, etc.) and practice breathing through them to see which are the most comfortable.
|Regular measuring of respiratory muscle strength is an important part of ALS care.|
The most permanent type of ventilation is the positive-pressure ventilator with a surgically created tracheostomy or trach. A ventilator is attached by a breathing hose to a tracheostomy tube, which delivers air through the neck into the trachea (windpipe) on a timed cycle.
Tracheostomy surgery (to create the opening into the trachea) is usually followed by several days or weeks of rehabilitation, during which caregivers learn how to clean and maintain the tracheostomy tube, change supplies and perform suctioning of mucus.
Many people on total ventilatory support can continue working, traveling, socializing and enjoying life. Today’s vents are small, portable, relatively quiet and can be carried on a wheelchair. For those still able to generate speech, a speaking valve often can be added to the inflatable cuff at the end of the tracheostomy tube, allowing air to travel to the vocal cords and enable speech.
In addition, a tracheostomy can provide a great feeling of safety. Permanent vents have alarms to alert caregivers to congestion or a disconnected tube. And invasive ventilation can return some energy as it relieves the exhaustion of poor sleep, prolonged coughing and labored breathing.
For more about the tracheostomy procedure and its effects, see the Breathe well section in Predicting Survival Time in ALS and Safe Harbor: Rediscovering Life on a Vent. In addition, A Tale of Two Vent Choices provides two personal accounts about using noninvasive and tracheostomy ventilation.
In 2011, a different type of breathing assistance device called a diaphragm pacing system was approved for “humanitarian use” in ALS by the U.S. Food and Drug Administration (FDA). The NeuRx Diaphragm Pacing System (DPS), developed by Synapse Biomedical, rhythmically stimulates breathing through an external pacer unit attached to electrodes that are surgically implanted in the diaphragm. To qualify for the DPS, a patient must have adequate preservation of the diaphragm muscle and phrenic nerves (the nerves that stimulate the diaphragm). The DPS does not slow or stop the progression of ALS, but it may delay the need for a tracheostomy, and may improve sleep and quality of life. Further studies are being conducted of its effectiveness in ALS. “Humanitarian use” approval by the FDA reflects the agency's opinion that the device does not pose "an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use." A Synapse video is available.
Another aspect of respiratory care that’s important in ALS is assisted coughing. As the coughing muscles weaken, it becomes harder to clear mucus from the airways and life-threatening mucus plugs can form. An assisted coughing device, which pushes air into the airways through a mask and then quickly reverses air flow, can help clear the airways and prevent infection. Doctors may recommend other methods to assist with coughing and clearing secretions from the airways.
Although ALS is considered a disease of the motor (movement) system, cognitive (thinking) and behavioral changes also occur in this disease. Some changes may be in response to the devastating nature of the disease, while others appear to be neurological in origin and to be part of the disease process itself.
It's been estimated that some 50 percent of those with ALS develop some alterations in thinking or behavior, although in most instances, symptoms are minimal and may be more distressing to relatives and caregivers than to the affected person. Although the medical profession often refers to these changes as frontotemporal dementia (FTD), which connotes memory loss (as in Alzheimer's disease), memory is generally well-preserved in ALS. Instead, the person with ALS may become unduly angry or irritable, or may be less considerate of others than one might expect him or her to be, or may exhibit poor judgment, apathy, ritualistic habits, new dietary preferences or other uncharacteristic behavior.
Some people with FTD symptoms lose insight into their actions and may not realize (even when it's pointed out to them) that they aren't thinking as clearly as before or that their behavior may be problematic.
Another phenomenon that sometimes occurs in ALS is known as pseudobulbar affect (PBA), in which the person experiences uncontrollable bouts of laughing or crying out of proportion to the situation. In 2010, the drug Nuedexta was approved to treat this symptom.
It's important for caregivers to know about possible cognitive symptoms in ALS, so that they can recognize the signs and not think that their loved one is simply "being difficult." Families can deal with the cognitive and behavioral changes associated with FTD by making modifications to the environment of the person with ALS that improve safety and organization; carefully describing symptoms to health care providers; helping their loved one make important decisions as early in the disease process as possible; and seeking support from others affected by ALS through online or in-person groups.
|Speech-generating devices help maintain communication.|
Speaking ability is lost when ALS affects the muscles of the mouth and throat that control speech and the muscles that help move air over the vocal cords.
For this reason, speech therapists and speech-language pathologists are vital members of the ALS care team. A speech therapist can teach the person with ALS special techniques for conserving energy and making speech more understandable. In some cases, a dentist can make a device called a palatal lift that can help compensate for certain types of weakness in the roof of the mouth.
In the early stages of ALS, speech therapists may suggest voice banking, which involves recording a number of common phrases that later can be programmed into a computer or communication device, enabling individuals with ALS to continue speaking in their own voice when they communicate via assistive technology.
Many therapists recommend being proactive about exploring communication options well before assistive technology is needed. A speech therapist can demonstrate how to use an alternative augmentative communication device, or AAC device.
Because learning to use such a device at later stages of ALS may be harder, individuals are encouraged to discuss options with their MDA clinic team and speech therapist early on, in order to proactively plan ways to stay in the conversation.
Muscle cramps, twitches and spasticity (tightness) are common in ALS.
The October 2009 American Academy of Neurology ALS Care Guidelines found insufficient data to support or refute any specific interventions for the treatment of these problems in ALS. However, the authors noted that in diseases such as multiple sclerosis and cerebral palsy, effective treatments for these problems include benzodiazepam, baclofen, dantrolene and tizanidine. These medications require a doctor's prescription.
Rest, repositioning, heat (such as from a microwaveable pad or warm bath) or gentle massage often are helpful in relieving the discomfort associated with muscle cramps, twitching and tightness.
Studies have estimated the prevalence of depression in people with ALS to be anywhere from 0 to 44 percent. However, when carefully structured interviews were used, the rate was consistently 9 to 11 percent.
According to the 2009 ALS Care Guidelines, there have been no controlled trials of treatment for depression in ALS, although there is consensus among experts that it should be treated. Many clinicians have found that antidepressants or anti-anxiety medication can have a positive effect.
Drooling, also known as sialorrhea, is common in ALS, because of weakness of the muscles of the mouth and throat. The October 2009 American Academy of Neurology ALS Care Guidelines say that the oral medication amitriptyline may be helpful in drying up saliva (thereby reducing drooling), as may injections of botulinum toxin type A into the salivary glands.
Radiation of the salivary glands to reduce saliva production also has been used for treatment of this condition when other measures fail. However, the guidelines note that side effects included redness, sore throat and nausea.
Recent evidence shows that maintaining one's weight may increase survival with ALS. Severe weight loss means muscle loss. Adequate fluid intake also is essential, for hydration, keeping saliva and mucus thin, and avoiding constipation.
Swallowing difficulties (dysphagia) are a prime cause of weight loss. As the muscles involved in chewing, moving food toward the back of the mouth, and swallowing weaken in ALS, eating and drinking become less pleasurable and more hazardous and time-consuming. Mouth and throat weakness can lead to choking and aspiration (inhaling food or liquid into the lungs), which can cause respiratory infection.
Other challenges include arm/hand weakness that limits self-feeding, decreased appetite, constipation, shortness of breath and nausea after eating, or fatigue due to the long and tiring process of eating.
Speech-language pathologists or therapists are also specialists in swallowing, since these functions involve the same muscles as speech. Some therapists specialize more in speech and others more in swallowing. Early solutions involve changing the consistency of food and liquids — usually thickening the liquids and avoiding large pieces of food — as well as changing swallowing techniques. (For more tips, see Nutrition Issues in the MDA ALS Caregiver's Guide and Meals for Easy Swallowing.)
If swallowing becomes difficult or unsafe and/or if eating takes a great deal of time and energy, a feeding tube may be recommended, often called a gastrostomy tube, g tube or PEG (percutaneous endoscopic gastrostomy) tube. The term "gastrostomy" refers to making a small incision in the stomach. It’s usually done percutaneously, which means “through the skin,” with the help of an endoscope, a medical instrument.
An October 2009 American Academy of Neurology report (see ALS Care Guidelines) found no ALS-specific indications for the timing of feeding tube placement. However, the report said the risk of placement increased when respiratory function declined below 50 percent of normal, and suggested that those with swallowing difficulties will be exposed to less risk if a feeding tube is placed when respiratory function is above 50 percent of normal.
If it’s still possible to swallow some foods or liquids safely, the person with ALS can continue to eat and drink by mouth even after placement of a feeding tube. But eating by mouth no longer has to be relied on as the only way to get adequate nutrition. This can be a relief to those who can’t take in enough calories by mouth because they get too tired or are afraid of choking or aspirating food.
Although getting a feeding tube initially feels like "ALS is winning," those who get them find they regain time and energy, and reduce the strain on their caregivers.
Occupational therapists specialize in helping people find and use tools to cope with progressive weakness in hand muscles. Special grips for writing and eating utensils, devices that fit over keys to make them easier to turn, zipper pulls and button hooks can help make weakening hands more functional, and help preserve independence in activities of daily living. Please consult with the occupational therapist on your MDA clinic team for more information.
The AAN guidelines found that visiting a multidisciplinary ALS clinic (one with many types of health professionals, such as an MDA/ALS center) can help people with ALS get the best possible care. The evidence showed that people with ALS who get care at a multidisciplinary clinic live longer, and may have a better quality of life than those who don't.
The drug riluzole (Rilutek) has a modest effect on slowing disease progression and prolonging survival. Four clinical trials have shown the drug prolongs survival by two to three months. However, five other studies using large databases spanning five to 10 years have suggested that riluzole might be associated with a prolonged survival of six months or even longer.
The drug appears to be safe, but it is expensive, and can cause fatigue, nausea and liver damage. The manufacturer suggests that people taking riluzole should avoid excessive intake of alcohol to minimize the risk of liver damage.
The damage ALS causes to the nervous system can lead to uncomfortable symptoms such as cramps and muscle twitching. Also, the immobility that results from ALS may put stress on muscles and joints, causing what is known as secondary pain.
Physicians may prescribe medications to treat these symptoms, as well as other symptoms often associated with ALS — including drooling, anxiety and depression, constipation (the result of reduced mobility and/or weakened abdominal muscles), sleep difficulties and pain associated with prolonged immobility.
Vitamin supplements may be recommended if swallowing difficulties result in reduced intake of nutrients. Reasonable doses of antioxidant supplements, such as vitamins C and E, are thought to have beneficial effects on the nervous system and overall health. However, high doses can do more harm than good.
Talk with your MDA clinic physician about medications and/or vitamin supplements that may be beneficial, and discuss dosage levels of supplements.
Fatigue, falling and increased difficulty walking often are experienced as ALS progresses. Avoiding falls is of paramount importance and can prevent trauma that could accelerate ALS disease progression. In addition to using mobility equipment to avoid falls, be sure to move area rugs, install grab bars and eliminate clutter wherever possible. Carry a cell phone when walking alone, to call for help if necessary.
In the early stages of ALS, mobility equipment such as a cane, walker or a supportive brace (orthosis) provide help in getting around. Weakness of muscles controlling the foot make it hard to move the foot or toe at will, causing foot drop that can lead to trips and falls. A lightweight ankle-foot orthosis, or AFO, keeps the foot from dropping and adds steadiness when walking. It can be slipped into different styles of shoes and concealed by wearing a sock over the brace, but it’s best worn with a supportive tie-up shoe.
When walking becomes difficult, riding in a manual wheelchair for long distances can conserve energy for short-distance walking, and also help prevent injury.
In later stages of the disease, a power wheelchair is usually the preferred means of mobility. When the time comes to use a power wheelchair full time, many with ALS find that they recover a large degree of independence.
Power chairs can be driven by a variety of means besides by hand, including by eyegaze and by "sip and puff" breath control. A “tilt-in-space” option on a wheelchair allows the seat to be positioned at a variety of angles, relieving pressure and helping prevent skin breakdown. Other valuable power chair options include elevating seats, chairs that turn into standers, motorized leg rests, custom seating and more.
Physical therapists, occupational therapists and equipment specialists have specialized knowledge about maintaining mobility and using equipment, and should be consulted prior to buying. Remember that insurance often will pay for only one mobility device during a set period of time, so it's important to consider upcoming needs before buying. If possible, it may be wise to borrow interim equipment, such as a mobility scooter or manual wheelchair, perhaps from your local MDA equipment program, and save insurance for big-ticket items like a power wheelchair.
Weakness in neck muscles also is associated with ALS. This results in difficulties in controlling or holding up the head, which leads to excessive fatigue and discomfort, not to mention frustration. Cervical collars may be recommended for support.
Very little research has been done on the subject of exercise and its role in ALS. In fact, it isn’t known whether exercises are beneficial for increasing muscle strength for people with ALS. (Many experts doubt that this is possible.)
However, it’s widely accepted among physicians and therapists that specific kinds of exercise help prevent the development of painful contractures (the permanent tightening of muscles) and can decrease the spasticity (intermittent or constant muscle tightness or spasms) that’s common in ALS.
Practicing the healthiest type of exercise for each stage of ALS will help maintain comfort and mobility. For some people, a moderate amount of daily walking in the early stages of ALS may be all that’s advisable. As the disease advances, it's very important to do daily range-of-motion and stretching exercises, either independently or with the help of a caregiver. Consult a physical therapist for the best exercise regime.
For more information, see the following sections in the MDA ALS Caregiver's Guide:
Planning early for the inevitable changes that occur over the course of ALS goes a long way toward maintaining function and independence for as long as possible and maintaining the highest possible quality of life. Such plans include addressing how home accessibility may be affected as the disease progresses. There are many ways to make adaptations or modifications that promote independence and safety in the home. A home visit by an occupational therapist to assess the environment is very helpful.
For more information, see your MDA clinic team.
Each occurrence of ALS is unique, and there is no clear-cut time frame for how an individual's disease will progress. For example, symptoms may appear gradually over time, or may occur rapidly and then plateau. The stages and strategies outlined below offer a general idea of the physical progression of ALS, the types of assistance needed as symptoms worsen and the role caregivers can play.
Intense research is being conducted in many areas related to ALS, from basic science seeking the roots of the disease, to therapy development to find effective treatments.
Research into familial (running in families) forms of the disease also may have relevance for sporadic (nonfamilial) forms, as all ALS cases — regardless of the form — present and develop along similar lines.
Many other medications and treatments are being tested for potential benefits in ALS. See Clinical Trials for details.
This section offers an overview and links to more information about ALS research targets and strategies, and research administration in ALS.
While some research teams have focused their attention on microglia, the nervous system's immune cells, others have focused more on astrocytes, a type of glial cell that normally provides support to motor neurons and other cells in the nervous system. Among their roles is clearing away a potentially toxic compound called glutamate from the area around nerve cells.
In late 2008, investigators showed that treating astrocytes alone can delay disease onset and extend survival in mice with a disease resembling ALS caused by mutations in the SOD1 gene.
In 2011, researchers showed that toxicity from astrocytes causes nerve cells to degenerate in new models for both inherited and noninherited forms of ALS.
Study results from two experiments reported in 2013 showed that astrocyte-associated harm to motor neurons may differ depending not only on whether the astrocytes carry a mutation, but on which mutation they carry as well.
Many genes, when mutated, can cause familial ALS. Among them are the SOD1 gene, the TDP43 gene and the FUS gene. In 2011, researchers discovered that abnormalities in the ubiquilin 2 gene can cause ALS, and a specific mutation in the C9ORF72 gene was found to be the most common genetic cause of the disease identified so far. (See Causes/Inheritance.) If someone with an ALS-causing gene mutation is the first in the family to show the disease, the disorder is classified as sporadic, since there is no family history. (This can happen when, for example, a parent carrying the ALS-causing mutation passes away of other causes before ALS develops but not before passing the mutation along to his or her children.)
However, research on the genetic factors that contribute to ALS, without necessarily causing it directly, is of great interest. Scientists suspect that a number of gene variants — probably in combination with other unknown factors — may increase susceptibility to sporadic ALS.
Several large gene association studies have been done comparing the DNA of people with and without ALS in hopes of uncovering genetic differences. These studies have pointed toward potential genetic targets for ALS research. For example, a large, multinational study to identify genetic risk factors associated with ALS found two DNA sequences on chromosomes 9 and one on chromosome 19 that are significantly different in people with and without the disease and may contribute to its development.
When scientists studied DNA from 915 people with ALS and 980 without the disease, they found expanded ataxin 2 genes in 43 (4.7 percent) of those with ALS and only 14 (1.4 percent) of those without it. They concluded that ataxin 2 expansions are significantly correlated with increased risk for developing ALS. Expanded ataxin 2 protein molecules appear to have toxic interactions with TDP43, another protein implicated in ALS, and blocking ataxin 2 interactions with TDP43 could become a new therapeutic avenue.
In ALS, there is some evidence that excess amounts of the neurotransmitter glutamate accumulate in the spaces around a nerve cell after it has completed its signaling function, causing problems for nerve cells the vicinity.
Normally, glutamate — a chemical transmitter of signals between nerve cells — is released by a sending neuron and docks on a receiving neuron. Once docked, it is quickly cleared away by glutamate transporter proteins, which are produced by neighboring cells in the nervous system called astrocytes. In ALS, something may go wrong with this glutamate clearance system. Some studies have suggested that, in ALS, a protein called EAAT2 may not be as efficient at clearing glutamate away from nerve cells as it should be. Other studies have suggested that a glutamate receptor, a docking site on the surface of motor neurons that receives glutamate, may be excessively permeable in this disease.
A drug specifically approved for the treatment of ALS by the U.S. Food and Drug Administration (FDA) is riluzole (Rilutek), which is believed to interfere with the action of glutamate.
In 2011, MDA awarded a grant to the biotechnology company Glialogix to test its new, experimental glutamate inhibitor called GLX1112 in mice with the SOD1-related familial form of ALS. The drug is designed to decrease excessive glutamate signaling through its interaction with a target on microglial cells, the immune cells of the nervous system.
There is a growing body of evidence that malfunction of the immune system is at least part of the ALS disease process. Research conducted at the ALS Therapy Development Institute (ALS TDI) and other labs has identified abnormal immune system overactivity in animal models of the disease, and ALS TDI investigators have observed it in blood samples from people with ALS.
It had been thought that motor neurons died alone in ALS. But, today, there is evidence that immune system cells in the nervous system called microglia are probably involved in their demise.
Blocking parts of the immune system is a strategy being pursued by ALS TDI researchers at ALS TDI. In 2011, the nonprofit biotech announced it would pursue testing in ALS mice of two experimental compounds that disrupt parts of the immune system. One, CDP7657, is an antibody fragment that inhibits the immune response by targeting a protein called CD40L. The other, CTLA4-FC, targets a signaling protein called CD86.
In 2013, ALS TDI launched a phase 2 trial of Gilenya (TDI 132, fingolimod) in ALS. Gilenya dampens the immune response and is approved by the FDA for the treatment of multiple sclerosis.
In addition, scientists at Neuraltus Pharmaceuticals are working on an experimental drug called NP001, which is designed to switch immune system cells from a damaging to a protective mode of action. In late 2010, Neuraltus announced encouraging findings showing that NP001 was safe and well-tolerated at four different dose levels in people with ALS and that, after a single intravenous dose, there was an improvement in blood levels of a biomarker thought to be involved in ALS progression.
Cellular proteins normally fold only in certain ways shortly after they're produced. When folding goes wrong, the result may be a highly toxic protein. In 2010, researchers found that misfolded SOD1 protein, unaccompanied by an SOD1 gene mutation, could underlie at least some cases of sporadic ALS.
Other proteins besides SOD1 may misfold and contribute to the disease as well. For example, the TDP43 and FUS proteins appear to misfold and form clumps (aggregate) in ALS-affected motor neurons even when the genes for these proteins are normal.
Normally, proteins called chaperones help coax other proteins to fold into the correct shape. Therefore, some scientists are working on increasing levels of these chaperone proteins. An experimental drug called arimoclomol is being tried in SOD1-related familial ALS with this mechanism in mind. A trial of arimoclomol in sporadic ALS also had been planned but did not go forward because of concerning data from toxicity studies in animals.
Another approach to targeting misfolded SOD1 is a type of molecule called an antisense oligonucleotide, which keeps toxic, misfolded SOD1 from being made. In 2012, the antisense-based drug ISIS-SOD1-Rx was found to be safe and well-tolerated in people with SOD1-related familial ALS in a phase 1 clinical trial. The drug was developed by Isis Pharmaceuticals with support from MDA.
In ALS, the cellular "energy factories" called mitochondria malfunction, although it isn't clear exactly where in the chain of events of the ALS disease process this malfunction occurs.
When mitochondria malfunction, they may fail to produce the needed energy for cells, and they may leak toxic substances called reactive oxygen species, subjecting cells to a kind of poisoning known as oxidative stress.
Unfortunately, coenzyme Q10, which combats oxidative stress, was not found to be helpful in people with ALS, even at high doses. (Coenzyme Q10 is an antioxidant, which is a substance that helps clean up free radicals.)
In 2010, however, MDA and the U.S. National Institutes of Health began conducting a large-scale study to probe the relationship between oxidative stress and ALS, with an eye to treatment development.
In 2013, the experimental drug dexpramipexole failed to show benefit in a phase 3 trial conducted in 943 people with ALS in 11 countries. Dexpramipexole had demonstrated neuroprotective properties in laboratory experiments, and appeared to show dose-related slowing of functional decline in people with ALS in an earlier phase 2 trial. It was thought to work by improving mitochondrial function.
MDA-supported researchers continue to study mitochondrial dysfunction in ALS, with an eye to determining whether it's a cause or a consequence of motor neuron loss and whether restoring mitochondrial function can alter the ALS disease course.
Stem cells can be thought of as cells that are in the very early stages of development, before they have become specialized (differentiated) to perform specific roles in tissues. They may be precursors to a specific cell types (such as muscle or nerve cells), or they may still retain pluripotency — the ability to develop into any of a number of different cell types.
In ALS, disease-affected stem cells are being used as models in which to study disease processes and screen potential therapies. For example, in 2011, researchers created a model of a type of ALS caused by mutations in the VAPB gene by causing skin cells from people with this form of the disease to revert to stem cells and then growing them in laboratory dishes.
Stem cells also are in development as cell-transplantation therapies. Theoretically, stem cells could be used to replace ALS-affected motor neurons; replace other types of cells, such as astrocytes; or release supportive proteins to help ailing nerve cells.
Early in 2012, the Israeli company BrainStorm Cell Therapeutics announced that its NurOwn stem cell technology appears safe and appears to have improved breathing, swallowing and muscle strength in four people with early-stage ALS, in a trial in Israel. In early 2013, BrainStorm, which plans to test its NurOwn stem cell technology in a trial in the United States in people with ALS, has advanced its phase 1-2 safety trial of adult stem cells to a phase 2a dose-escalating trial.
Another biotechnology company, Neuralstem reported in 2012 that its spinal cord stem cells, and the surgical technique used to transplant them, proved to be safe and well-tolerated in a phase 1 clinical trial in 12 people with ALS. This first U.S.-based trial of neural stem cells in ALS opened at the MDA/ALS Center at Emory University in January 2010.
Many companies and institutions outside the United States (and a few inside) falsely advertise that they can cure ALS with stem cells. So far, there are no stem-cell-based treatments for ALS that are known to be either safe or effective, although Neuralstem's technology appears to be safe so far. Some companies may not even be injecting stem cells. Other may be using stem cells that are too undifferentiated and can be dangerous, while others may be using cells that are too differentiated and are no longer able to join existing tissues. Bottom line: Advertised stem cell therapies should be approached with great caution.
In 2008, MDA established a nationwide consortium of five MDA-supported ALS centers that would each receive $100,000 per year to fund the infrastructure necessary for collaboration on clinical trials in ALS. The centers are located in Atlanta, Boston, Houston, New York and San Francisco.
In early 2013, MDA launched a neuromuscular disease registry through its national network of clinics. Through the registry, MDA aims to improve survival and quality of life for people with ALS and other neuromuscular diseases, and to expedite clinical trials and help make them more efficient. The Registry is being piloted at 25 MDA clinics to start; to learn more, check with your local MDA office.
In 2010, the U.S. Centers for Disease Control and Prevention opened the National ALS Registry to compile a large database of information about the incidence and prevalence of ALS, how the disease develops, and what types of treatments and interventions are beneficial.
People with ALS and/or their caregivers are encouraged to register at cdc.gov/als, where they will be asked to fill out short surveys about their and their families' health, their military background, and their environmental and occupational exposures.
In 2011, the ALS Research Collaboration, a University of Miami-based team dedicated to the study of familial (inherited) ALS, launched the fALS Connect online familial ALS registry. The developers of this registry aim to connect families affected by familial ALS with scientists who study the disease, in an effort to accelerate development of treatments and cures. Membership is open to those who have familial ALS and their blood relatives.
A clinical trial is a test in humans of an experimental medication or therapy. Clinical trials are experiments, not treatments, and participation requires careful consideration.
Although it's possible to benefit from participating in a clinical trial, it's also possible that no benefit — or even harm — may occur. Keep your MDA clinic doctor informed about any clinical trial participation. (Note that MDA has no ability to influence who is chosen to participate in a clinical trial.)
For a more refined list of ALS clinical trials, visit ClinicalTrials.gov, a registry of federally and privately supported clinical trials in the United States and around the world. Select "Search for Clinical Trials," and follow the instructions to narrow down your search results.