About ALS

Amyotrophic Lateral Sclerosis (ALS, sometimes called Lou Gehrig's Disease) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. As a motor neuron disease, the disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, develop fasciculations (twitches) because of denervation, and eventually atrophy because of that denervation. The patient may ultimately lose the ability to initiate and control all voluntary movement except of the eyes.

Cognitive function is generally spared except in certain situations such as when ALS is associated with frontotemporal dementia. However, there are reports of more subtle cognitive changes of the frontotemporal type in many patients when detailed neuropsychological testing is employed. Sensory nerves and the autonomic nervous system, which controls functions like sweating, generally remain functional.

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Epidemiology, causes and risk factors

ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. One to 2 people per 100,000 develop ALS each year. ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women.

Cause and Risk Factors

Scientists have not found a definitive cause for ALS and the onset of the disease has been linked to several factors, including: a virus; exposure to neurotoxins or heavy metals; DNA defects; immune system abnormalities; and enzyme abnormalities. Surgeries involving the spinal cord have also been thought to play a role in the onset of ALS due to the disruption of nerve fibers. There is a known hereditary factor in familial ALS (FALS); however, there is no known hereditary component in the 90-95% cases diagnosed as sporadic ALS. An inherited genetic defect linked to a defect on chromosome 21 is believed to cause approximately 40% of familial cases of ALS. This mutation is believed to be autosomal dominant. The children of those diagnosed with familial ALS have a higher risk factor for developing the disease; however, those who have close family members diagnosed with sporadic ALS have no greater a risk factor than the general population.

Symptoms

Initial Symptoms

The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest symptoms are obvious weakness and/or muscle atrophy. This is followed by twitching, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The twitching, cramping, etc. associated with ALS is a result of the dying muscle, therefore these symptoms without clinical weakness or atrophy of affected muscle is likely not ALS.

The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people experience "limb onset" ALS. In some of these cases, symptoms initially affect one of the legs, and patients experience awkwardness when walking or running or they notice that they are tripping or stumbling more often. Other limb onset patients first see the effects of the disease on a hand or arm as they experience difficulty with simple tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally the symptoms remain confined to one limb; this is known as monomelic amyotrophy.

About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly. Speech becomes garbled and slurred. Nasality and loss of volume are frequently the first symptoms. Difficulty swallowing, and loss of tongue mobility follow. Eventually total loss of speech and the inability to protect the airway when swallowing are experienced.

Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Patients experience increasing difficulty moving, swallowing, and speaking or forming words. Symptoms of upper motor neuron involvement include tight and stiff muscles and exaggerated reflexes including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign (the large toe extends upward as the sole of the foot is stimulated) also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). Around 15–45% of patients experience pseudobulbar affect, also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor expressions of emotion.

To be diagnosed with ALS, patients must have signs of both upper and lower motor neuron damage that cannot be attributed to other causes.

Emerging Symptoms

Although the sequence of emerging symptoms and the rate of disease progression vary from person to person, eventually patients will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. Difficulty swallowing and chewing impair the patient's ability to eat normally and increase the risk of choking. Maintaining weight will then become a problem. Because the disease usually does not affect cognitive abilities, patients are aware of their progressive loss of function and may become anxious and depressed. A small percentage of patients go on to develop frontotemporal dementia characterized by profound personality changes; this is more common among those with a family history of dementia. A larger proportion of patients experience mild problems with word-generation, attention, or decision-making. Cognitive function may be affected as part of the disease process or could be related to poor breathing at night (nocturnal hypoventilation). Health care professionals need to explain the course of the disease and describe available treatment options so that patients can make informed decisions in advance.

As the diaphragm and rib cage weaken, forced vital capacity and inspiratory pressure diminish. In bulbar onset ALS, this may occur before significant limb weakness is apparent. Bilevel positive pressure ventilation (frequently referred to by the tradename BiPAP) is frequently used to support breathing, first at night, and later during the daytime as well. It is recommended that long before BiPAP becomes insufficient, patients (with the eventual help of their families) must decide whether to have a tracheostomy and long term mechanical ventilation. Most patients do not elect this route, and instead choose palliative hospice care at this point. Most people with ALS die of respiratory failure or pneumonia, not the disease itself.

ALS predominantly affects the motor neurons, and in the majority of cases the disease does not impair a patient's mind, personality, intelligence, or memory. Nor does it affect a person's ability to see, smell, taste, hear, or feel touch. Control of eye muscles is the most preserved function, although some patients with an extremely long duration of disease (20+ years) may lose eye control too. Unlike multiple sclerosis, bladder and bowel control are usually preserved in ALS, although as a result of immobility and diet changes, intestinal problems such as constipation can require intensive management.

Diagnosis

No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.

Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis.

Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.

Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease, syphilis, and tick-borne encephalitis viruses can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, and spinal muscular atrophy also can mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis. There have been documented cases of a patient presenting with ALS-like symptoms, having a positive Lyme titer, and responding to antibiotics. Lyme disease is particularly difficult to diagnose.

Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients should always obtain a second neurological opinion.

Treatment

No cure has yet been found for ALS. However, the FDA has approved the first drug treatment for the disease: Riluzole (Rilutek). Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects. However, this first disease-specific therapy offers hope that the progression of ALS may one day be slowed by new medications or combinations of drugs. A small, open-label study recently suggested that the drug lithium which traditionally is used for the treatment of bipolar affective disorder may slow progression in both animal models and the human form of the disease. However, further research is needed to establish whether the effect is real or not.

Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals such as physicians; pharmacists; physical, occupational, and speech therapists; nutritionists; social workers; and home care and hospice nurses. Working with patients and caregivers, these teams can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.

Physicians can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, and constipation. Pharmacists can advise on best use of medications.

Physical therapy and special equipment such as assistive technology can enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical therapists can recommend exercises that provide these benefits without overworking muscles. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients remain mobile.

ALS patients who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) and/or low tech communication techniques such as alphabet boards or yes/no signals. These methods and devices help patients communicate when they can no longer speak or produce vocal sounds. With the help of occupational Therapists, speech-generating devices can be activated by switches or mouse emulation techniques controlled by small physical movements of, for example, the head, finger or eyes.

Patients and caregivers can learn from speech-language pathologists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.

Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheotomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck. Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support. It must be pointed out that some patients under long-term tracheostomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheostomy tubes (leak ventilation) are able to speak. This technique preserves speech in some patients with long-term mechanical ventilation.

Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Home nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving feedings, and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.

Prognosis

Regardless of the part of the body first affected by the disease, it is usual for muscle weakness and atrophy to spread to other parts of the body as the disease progresses. It is important to remember that some patients with ALS have an arrested course with no progression beyond a certain point despite extensive follow-up. Such a pattern is particularly true for young males with predominant upper limb weakness especially on one side (so-called monomelic or Hirayama type motor neuron disease). Eventually people with ALS will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. In later stages of the disease, individuals have difficulty breathing as the muscles of the respiratory system weaken. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. However, about 10 percent of those individuals with ALS survive for 10 or more years.

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For more information on ALS we encourage you to visit the ALS Association at alsa.org