Amyotrophic Lateral Sclerosis (Lou Gehrig Disease)

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of the part of the nervous system that controls voluntary movements. It is sometimes called Lou Gehrig disease for the famous baseball player who died of the disease. The muscles become progressively weaker, and the condition eventually leads to paralysis and death.

ALS is one of a group of diseases known as motor neuron diseases. Neurons are nerve cells, and motor neurons are neurons that control movement.

• Movement occurs when neurons in the brain (upper motor neurons) send messages to neurons in the spinal cord (lower motor neurons). The lower motor neurons relay these messages to the specific muscles that carry out the movement.
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• In some motor neuron diseases, only the upper motor neurons are affected, or only the lower motor neurons. In ALS, however, both upper and lower motor neurons are affected.
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• The neurons die and stop sending messages to muscles. The muscles are unable to function without these messages and gradually become weaker. They waste away (atrophy) and twitch (fasciculate).
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• Eventually all voluntary movement is lost, and muscles become paralyzed.

The loss of strength and control follows different patterns in different people.

• Some people lose control of one or both legs first. They may have trouble walking or running or become clumsy, tripping or falling.
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• Others notice a problem with a hand or arm first, having problems with simple tasks such as writing or buttoning a shirt.
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• In some, speech or swallowing is the first thing affected.
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• In every case, the weakness and disability spread to almost every part of the body.
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• The diaphragm is a muscle under the lungs that partly controls their expansion as they take in air. When the chest muscles and diaphragm become too weak, the person is no longer able to breathe on his own. This is called respiratory failure and is by far the leading cause of death for people with ALS.
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• Most people with ALS die within 5 years of the onset of symptoms.

ALS does not affect a person’s mental abilities or senses. It does not impair intelligence, reasoning, memory, or personality. Senses such as vision and touch are not lost. Most people retain their ability to move their eyes. Bowel and bladder control are not impaired.

ALS is diagnosed in about 5000 people each year in the United States, where about 20,000 people are believed to have the condition. It affects all races and ethnic groups. The disease can occur at any age but is most common in people aged 40-60 years. Men are affected more often than women.

No cure is available for ALS. The effects of the disease are not reversible. Research is focused on finding the cause of the neuron degeneration and stopping it.

We do not know exactly what causes ALS. Although about 10% of cases of ALS are hereditary (run in families), the other 90% are not. A mutation of a gene called SOD1 has been identified in some of the hereditary cases, but we do not know what role the mutation plays in the disease. 

Using an evidence-based approach, smoking emerged as a more likely than not risk factor for ALS based on two excellent studies by Kamel et al and Nelson et al. Smoking has broad public health impact, no redeeming features, and is a modifiable risk factor. Evidence supported the conclusion that the following were probably not risk factors for ALS: trauma, physical activity, residence in rural areas, and alcohol consumption.

ALS may begin as weakness, awkwardness, or atrophy in one or more limbs. It may start as a difficulty swallowing or speaking. The symptoms may be very subtle at first, and may be overlooked. Common symptoms include the following:

• Difficulty standing, walking, or running
  
  
• Clumsiness – Frequent tripping or falls
  
  
• Difficulty with fine hand motions such as buttoning, writing, turning a key in a lock
  
  
• Atrophy of hand muscles
  
  
• Atrophy of tongue
  
  
• Difficulty chewing food
  
  
• Difficulty swallowing (dysphagia)
  
  
• Difficulty speaking
  
  
• Oversensitive gag reflex
  
  
• Difficulty forming words (dysarthria)
  
  
• Weakness and atrophy in specific muscles
  
  
• Tight, stiff muscles (spasticity)
  
  
• Muscle cramps
  
  
• Muscle twitching visible under skin (fasciculations)

There is evidence for frontal lobe dysfunction in many patients with ALS. Usually, it is detectable only when looked for specifically with focused tests. However, in a minority of patients, clinically significant cognitive impairment becomes evident, with a continuum of abnormalities extending all the way to frank frontotemporal dementia. In addition to difficulties in planning and sequencing (the most common manifestations of “executive dysfunction” due to frontal lobe disease) some patients may express an otherwise inexplicable nonchalance, or lack of insight, into their situation and its impact on themselves and their loved ones, and others, fortunately rarely, may become less friendly than their usual selves. These aspects of ALS when present may pose major challenges to caregivers and health care personnel alike, and they may be associated with shorter survival. 

Depression and anxiety may occur in patients with ALS. Though difficult to prove, these are likely part of the disease process itself, rather than mere reactions of the patients to their condition. Depression and anxiety are treatable.  

Finally, some patients with ALS frequently exhibit a pseudobulbar affect, manifesting as involuntary, uncontrolled outbursts of crying or laughter, which is distinct from their underlying mood. 

As the disease progresses, the person with ALS loses the ability to carry out everyday activities such as dressing, eating, and working. Eventually getting out of bed at all becomes impossible without assistance. The person becomes restricted to a wheelchair or bed. (Bedsores can be a problem.) As the respiratory muscles weaken, breathing becomes more and more difficult. The risk of pneumonia increases.

Most hereditary and sporadic (nonhereditary) cases of ALS have similar symptoms and course.

The signs and symptoms of ALS are often very subtle. They can be vague and nonspecific. This means that they could be caused by many different conditions.

• Any progressive difficulty in carrying out a normal activity such as walking, writing, or swallowing, warrants an evaluation by your doctor.

• Occasional clumsiness or muscle cramping is not unusual and does not mean that you have ALS.

No one test gives a definitive diagnosis of ALS. If you are having symptoms that suggest ALS, your health care provider will conduct a complete workup. He or she will conduct a detailed medical interview and physical examination and review the results of various tests before arriving at a diagnosis. At any time during the workup or treatment planning, your health care provider may refer you to a specialist in diseases of the nervous system (neurologist).

Your health care provider will ask you many questions about your symptoms; your medical problems now and in the past; the medical problems of your family members; the medications you take; your work, military, and travel experiences; your habits and lifestyle; and probably others. A detailed physical examination will focus on your mental abilities, movements, sensations, and reflexes.

Lab tests

There is no lab test that confirms the diagnosis of ALS. Your health care provider may order a number of blood tests. Many of these are used to rule out specific conditions that may cause the symptoms you are having. These conditions include infections, metabolic problems, and autoimmune conditions. It is important to distinguish ALS from other conditions because many of these conditions can be improved with appropriate treatment.

Imaging studies

You may undergo MRI of the brain or spinal cord. MRI findings are normal in ALS, but these studies may be needed to rule out other conditions whose symptoms are similar to those of ALS.

Other tests

Needle electromyography (EMG) and nerve conduction studies are the tests of choice for confirming the diagnosis of ALS. They also can rule out certain other conditions that may be confused with ALS.

• EMG is a method of recording electrical activity in muscles. Certain EMG findings support the diagnosis of ALS.
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• Nerve conduction velocity (NCV) measures the impulses traveling through nerves between the spinal cord and muscles. This test can distinguish between ALS and other conditions with similar symptoms.
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• These tests are conducted by a physician who specializes in electrophysiologic measurements.

In certain circumstances, a muscle biopsy is done to rule out muscle diseases that may have similar symptoms. A biopsy is removal of a tiny piece of tissue. The tissue is tested and examined under a microscope by a specialist called a pathologist. The pathologist reports his or her findings back to the physician who ordered the biopsy.

The goals of medical treatment are to relieve symptoms and complications, maintain muscle functions and movement, and delay paralysis and disability for as long as possible.

|Self-Care at Home|

ALS is a slowly progressive disease causing gradual disability. Once you begin to lose muscle function, you also begin to lose the ability to care for yourself.

• Gradually you become dependent on caregivers to take care of your bodily needs. At first, for example, you may have difficulty walking; later you will require help transferring from bed to chair or wheelchair. Eventually even the smallest movement requires assistance.
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• The medical care team may include the primary care provider, specialist physicians, physical therapist, speech and communication therapist, respiratory therapist, social worker, nutritionist, and nurses. This team will provide much help in preparing you and your family to cope with this disability.
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• Spouses and other relatives bear the major responsibility for day-to-day care.
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• Home health aides can help relieve the stress of providing this round-the-clock care. They help by bathing, dressing, transferring, and feeding you as well as providing other services that prevent complications and provide comfort.

|Medical Treatment|

No cure is available for ALS. However, a medication called riluzole (Rilutek) has become available.

• This medication apparently slows damage to motor neurons by decreasing levels of a substance called glutamate that is thought to have a role in motor neuron degeneration.
  
  
• This drug has been shown to prolong life or delay ventilatory failure by two to three months in patients with ALS.
  
  
• It does not reverse damage already done to motor neurons.

The remainder of medical treatment is focused on relieving symptoms, maintaining function for as long as possible, and coping with loss of function.

• Regular exercise and a physical therapy program can strengthen muscles and reduce spasticity. This helps maintain movements for as long as possible.
  
  
• Speech therapy can help maintain speech for as long as possible and introduce other methods of communication. Computerized devices may help you communicate when you can no longer speak.
  
  
• Medications such as baclofen (Lioresal) and tizanidine (Zanaflex) may be used to relieve severe spasticity.
  
  
• Medications also may be prescribed to relieve pain (if any), depression, anxiety, sleep problems, and constipation.
  
  
• Diet needs to be adjusted to maintain adequate nutrition. Percutaneous tube feedings to the stomach are recommended when eating becomes an arduous task (takes more than an hour to complete the meal, or patient gives up before finishing), or when patients find they are choking on their food, or if they begin to lose weight rapidly.

Breathing support becomes necessary when you encounter symptoms of ventilatory failure. Often these result first in disrupted sleep. A patient may become aware of this first by noticing excessive sleepiness, or tiredness, during the day, or by waking up with headaches. Later, patients may become short of breath if they lie down or with the smallest of activities. Non-invasive ventilatory support (Bi-PAP) can be used to support breathing during the night, and also, in more advanced disease, to give the breathing muscles a rest during the day. 

Nutritional support and judicious use on non-invasive ventilatory support may extend life by up to 12 months on the average and result in improved patients’ quality of life. 

Invasive ventilatory support is required when patients can no longer breathe without assistance or if excessive secretions preclude use of non-invasive ventilatory support. 

• Usually a mechanical ventilator is connected to the trachea (airway) through a small, permanent hole in the neck called a tracheostomy. The tracheostomy is created by a surgeon.
  
  
• The biggest problem for a person on a ventilator is keeping the airway clear of natural secretions such as saliva and mucus.
  
  
• If not cleared, these secretions can be “aspirated,” or breathed into the lungs. There they cause problems such as infections and pneumonia.
  
  
• A respiratory therapist can help prevent aspiration by regular suctioning and chest percussion.
  
  
• These secretion management techniques can be learned by caregivers and home health aides.

Only a small minority of patients choose to receive invasive ventilatory support because of its requirements for 24-hour care in the context of a lifestyle that most, but not all, patients do not choose for themselves. However, some patients on long-term permanent ventilatory support have reported meaningful quality to their lives.

|Medications|

Riluzole (Rilutek) helps slow motor neuron damage and delay muscle paralysis and loss of function. If you are taking this drug, you will require regular blood tests during the first several months of treatment to detect possible liver damage, decreased neutrophils (white blood cells), and other harmful effects. To allow riluzole to be properly absorbed from your stomach, you should take the drug on an empty stomach (1 hour before or 2 hours after meals). Common side effects when starting the drug include nausea, dizziness, diarrhea, loss of appetite, and drowsiness.

|Surgery|

There is no surgical treatment for ALS. The surgeon is called in to create the tracheostomy when you require help to breathe.

|Follow-up|

Once ALS is diagnosed, you will require regular visits with the medical team that is providing your care. These visits will monitor the course of the disease and the effects of treatment. They will also alert the medical team to needs for changes or additions to the treatment regimen.

|Prevention|

There is no known way to prevent ALS. This is one of the goals of ongoing research on ALS.

|Outlook|

Right now, no cure is available for ALS. It results in the death of affected patients. Most people with ALS die within 5 years of the first symptoms, although a few people have lived as long as 10 years. Most people with ALS die of respiratory failure or infections related to respiratory disability.

If you have ALS, you should take the opportunity to express your wishes about medical care, estate planning, and personal issues while you are still able.

• Preferences concerning medical care at the end of life should be clarified early and documented in your medical chart. Your spouse and other close family members should understand your wishes. Early clarification of these wishes prevents conflicts later when you are not able to speak for yourself.
  
  
• You should consult a lawyer as early as possible. Personal affairs should be settled. Later in the disease, you may not be able to sign papers or even communicate your wishes.

|Support Groups and Counseling|

Living with ALS presents many new challenges, both for the affected person and for family and friends.

• You will naturally have many worries about the disabilities that come with the disease. How long you will be able to care for your family and home, hold your job, and continue the friendships and activities you enjoy? You worry about how your family will cope with the demands of your care. You wonder how they will manage when you are no longer able to contribute. You may feel anxious about death.
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• Your loved ones also feel anxious about your death and how much they will miss you. They wonder how they will care for you through your illness. Money is almost always a concern.
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• Many people in this situation feel anxious and depressed, at least sometimes. Some people feel angry and resentful; others feel helpless and defeated.

For both you and your caregivers, talking about feelings and concerns may help.

• Your friends and family members can be very supportive. They may be hesitant to offer support until they see how you are coping. Don't wait for them to bring it up. If you want to talk about your concerns, let them know.
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• Some people don't want to "burden" their loved ones, or prefer talking about their concerns with a more neutral professional. A social worker, counselor, or member of the clergy can be helpful if you want to discuss your feelings and concerns about having ALS. Your primary care provider or neurologist should be able to recommend someone.
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• You or your family members may be helped profoundly by talking to other people who have the disease or to their family members. Sharing your concerns with others who have been through the same thing can be remarkably reassuring. This is why support groups exist. Support groups offer the opportunity for people whose lives are affected by ALS to get together, whether in person, on the telephone, or on the Internet.
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• Because ALS is relatively rare, finding a support group in your area may be difficult, unless you live near a large medical center with many medical specialists. There are groups on the Internet that can help you find the support you need.

For more information about support groups, contact these agencies:

• ALS Association – (800) 782-4747 or (818) 880-9007
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• Les Turner ALS Foundation – (888) ALS-1107 or (847) 679-3311
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• Family Caregiver Alliance, National Center on Caregiving - (800) 445-8106
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• Doctor’s Group
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• Supportpath

ALS Association
27001 Agoura Road, Suite 150
Calabasas Hills, CA 91301-5104
(818) 880-9007
(800) 782-4747  (Information and referrals)
 
American Speech-Language-Hearing Association (ASHA)
10801 Rockville Pike
Rockville, MD 20852
(800) 638-8255
 
Les Turner ALS Foundation
8142 North Lawndale Avenue
Skokie, IL 60076
(888) ALS-1107 or (847) 679-3311
 
Muscular Dystrophy Association (MDA)
ALS Division
3300 East Sunrise Drive
Tucson, AZ 85718-3208
(820) 529-2000 or (800) 572-1717
 
Project ALS
511 Avenue of the Americas, Suite 341
New York, NY 10011
(800) 603-0270 or (212) 969-0329

|Web Links|

ALS Association

American Speech-Language-Hearing Association, Amyotrophic Lateral Sclerosis

Doctor’s Guide, Patient Resources, ALS (Lou Gehrig's Disease)

Les Turner ALS Foundation

Muscular Dystrophy Association, ALS Division, Amyotrophic Lateral Sclerosis (ALS)

National Institute of Neurological Disorders and Stroke, National Institutes of Health, Amyotrophic Lateral Sclerosis Fact Sheet

Project ALS

amyotrophic lateral sclerosis, ALS, glutamate, Lou Gehrig’s disease, Lou Gehrig disease, symptoms of ALS, symptoms of amyotrophic lateral sclerosis, Lou Gehrig's disease symptoms, motor neuron disease, movement, muscle atrophy, nerve disorders, neurotransmitter, paralysis, paralyzed, respiratory failure, weakness, voluntary movement, neurons, nerve cells, SOD1 gene

Author: Fernando Dangond, MD, Associate Neurologist, Brigham and Women's Hospital; Assistant Professor, Department of Neurology, Harvard Medical School.

Editors: Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, University of Pittsburgh Medical Center - Shadyside, Clinical Associate Professor, Department of Neurology, University of Pittsburgh School of Medicine; Mary L Windle, Pharm D, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, .com, Inc; Carmel Armon, MD, MHS, MSc, Professor of Neurology, Tufts University School of Medicine, Chief, Division of Neurology, Baystate Medical Center, Springfield, Massachusetts.