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Imagine a healthy man, sixty years old, recently retired, with many years left to spend with his wife, four children, ten grandchildren, and two great-grandchildren. Then one day he begins experiencing difficulty swallowing and slurred speech. After being told by his daughter that these could be symptoms of a stroke, he turns to his doctor for answers. As his swallowing and speech worsen, each diagnostic test is inconclusive. Finally, after several months of

increasing frustration and decreasing health, he is diagnosed with amyotrophic lateral sclerosis, or ALS. Within two months, he is in a wheelchair with a surgically placed feeding tube. Six months after being diagnosed, he passes away in his sleep from respiratory failure. He was sixty-one years old. The National Institute of Neurological Disorders and Stroke (NINDS) estimates that approximately 30,000 people in the United States are currently living with ALS, with an average of fifteen new cases diagnosed every day. ALS is always fatal and progresses so rapidly that, on average, the death rate is equal to the rate of diagnosis. Although there is currently no cure for ALS, physicians and researchers are working diligently to pinpoint the etiology of this tragic disease and to eventually develop a treatment and a cure. The term amyotrophic lateral

sclerosis is derived from the Greek language and describes the physiological effects that the disease has on the body. Amyotrophic means without nourishment to muscles and refers to the atrophy, or shrinking, of muscles from the loss of nerve signals and resulting disuse. Lateral means to the side and refers to the damage in the nerve tracts on either side of the spinal cord. Sclerosis means hardened and refers to the hardened state of the spinal cord that occurs in the advanced stages of ALS. Commonly called Lou Gehrigs disease since the famed baseball player was diagnosed with the illness in 1939, amyotrophic lateral sclerosis is a rapidly progressive, debilitating

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disease of the nervous system. ALS attacks the motor neurons located in the brain and spinal cord which are responsible for voluntary muscle movement and control. Upper motor neurons in the brain transmit signals to lower motor neurons in the brain stem and spinal cord, and from the spinal cord these signals travel to specific muscles. ALS causes a progressive degeneration of both upper and lower motor neurons, which eventually leads to their death. With the death of these neurons, the brain loses its ability to deliver the chemical signals needed to initiate and control voluntary muscle movement. The muscles involved will initially become very weak and eventually succumb to total paralysis, resulting in atrophy or wasting away of the muscle. Since the neuron death resulting from ALS only affects voluntary muscles, involuntary muscle function is left intact. This includes cardiovascular and digestive system functions, bowel and bladder function, and sexual function. The senses are not affected, nor are intellect or cognitive function. The true cause of ALS is not known, and the scientific and medical communities currently do not know why ALS strikes some people but not others. Researchers have studied several possible causes of ALS including autoimmune responses, exposure to toxic or infectious agents, and dietary deficiencies, but so far there is not enough evidence to contribute ALS to any of these factors. Although the majority of ALS cases are sporadic, approximately 10% of cases are hereditary and considered familial forms of ALS. In 1993, scientists at the NINDS isolated a mutation in the gene that produces an enzyme called superoxide dismutase 1. SOD1 is known to be a powerful antioxidant that protects the body from highly reactive molecules called free radicals. These molecules can cause random damage to DNA if allowed to accumulate.

Researchers are not yet sure how the SOD1 gene mutation contributes to motor neuron

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degeneration, but the belief is that the mutation may lead to an accumulation of free radicals which could soon be linked to the development of ALS. This mutation has only been found in hereditary cases of ALS. Some studies have also looked at excess glutamate as a potential source of motor neuron degeneration. Glutamate is the most abundant excitatory neurotransmitter found in the central nervous system and is involved in most cognitive brain functions. Researchers have found that ALS patients tend to have increased glutamate levels in their blood and cerebrospinal fluid. There are studies that show an increase in neuron death due to long-term exposure to excessive amounts of glutamate, but scientists are still trying to determine what leads to the buildup of glutamate in ALS patients. The symptoms of ALS generally appear in one of two ways. In limb-onset ALS, the first symptom many patients notice is weakness in their arms or legs, making simple tasks such as walking or using their hands quite difficult. As upper motor neurons are damaged and die patients will begin to experience muscle stiffness, cramping, and exaggerated reflexes. Lower motor neuron damage results in muscle wasting, twitching, diminished reflexes, and additional weakness. The muscles controlling speech and swallowing will soon be affected, causing slurred speech and an eventual inability to eat. As the progression of ALS occurs, the affected muscles will begin to atrophy (shrink or thin) due to disuse. The patient will eventually experience total paralysis of all voluntary muscles, including those of the respiratory system such as chest wall muscles and the diaphragm, leaving the patient unable to breathe on their own. Approximately 75% of ALS cases begin as limb-onset, and death generally occurs in three to five years from the onset of symptoms.

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In contrast to limb-onset ALS, around one-quarter of diagnosed patients present with bulbar-onset ALS. In the 75% of patients afflicted with limb-onset ALS, 75-80% of these will go on to develop bulbar symptoms during the course of the disease. It is called this because the bulbar motor neurons, located in the medulla oblongata portion of the brainstem, are the first neurons affected by the disease. Bulbar motor neurons control the muscles responsible for speaking, swallowing, and facial expression. The tongue is usually the first muscle affected, so many patients will initially present with slurred speech or difficulty forming words. They also experience dysphagia, or difficulty swallowing, drooling, and may have trouble closing their mouths and eyes. This type of ALS onset seems to progress very quickly, with the respiratory muscles being affected soon after the first symptoms develop. These patients are prone to aspirating their food and drink due to inadequate abilities to chew and swallow, and are at a high risk for developing aspiration pneumonia. In fact, a large percentage of bulbar-onset ALS patients die from this complication. Depending on which part of the brain stem and which cranial nerves are affected, the patient may also experience emotional changes such as uncontrollable laughing or crying. Bulbar-onset ALS has a life expectancy significantly shorter than limb-onset ALS, ranging from six to thirty-six months. Only around 20% of bulbar-onset ALS patients survive beyond two years. When it comes to diagnosing this disease, there is no diagnostic tool or laboratory test that will show ALS. Genetic screening may identify carriers of gene mutations if the patient demonstrates a family history of ALS, but as stated earlier this is a very small percentage of diagnosed cases. In most cases, a diagnosis is made simply by ruling out other neurological disorders and motor neuron diseases. While there is no definitive diagnostic test, there are certain signs and symptoms a physician will look for. The presence of both upper motor neuron

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and lower motor neuron involvement is looked for, and is normally strongly suggestive of ALS. When symptoms first appear and an immediate cause is not determined, the patient will most likely be referred to a neurological specialist. At this point, there are several tests the neurologist can conduct to diagnose or rule out other possibilities. Many other neurological diseases and disorders can be effectively treated and controlled so it is important to consider all possibilities when looking for an answer. The physician may perform an electromyography (EMG), which is a technique used to detect electrical activity in muscles. An EMG is done by inserting small needles into muscles and having the patient flex those muscles one at a time to measure the level of, or lack of, electrical activity. While decreased activity can be indicative of other conditions, it can support a diagnosis of ALS. The physician will usually choose to perform a nerve conduction test during the same visit as the EMG. Nerve conduction tests are used to measure the speed that an electrical impulse travels through a nerve, and will determine nerve damage or destruction. During this procedure, electrodes are placed on the surface of the skin over the particular nerves that the physician wishes to measure. One electrode will deliver a mild

electrical shock, while another electrode records the result. Together, these procedures help to detect the presence, location, and degree of nerve and muscle damage due to a condition or disease. The patient may also undergo magnetic resonance imaging (MRI) to get a detailed picture of the brain and spinal cord. This noninvasive test will often appear normal in patients who truly have ALS, but many other conditions that could be the cause of the presenting symptoms may be seen with the MRI. Other tests ordered may include a complete round of blood and urine tests, as well as muscle and nerve biopsies. Once again, since no test can definitively diagnose ALS, these procedures are strictly used to rule out any other possible diseases or conditions before a diagnosis of ALS is made.

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One of the reasons a diagnosis of ALS is so heartbreaking is because there is no known cure for the disease. The Food and Drug Administration has currently only approved one drug, riluzole, for the treatment of ALS. Riluzole decreases the release of glutamate, and is believed to reduce damage to upper and lower motor neurons. The medication will not reverse damage that has already been done and has not been proven to slow the progression, but it has been shown to prolong survival by several months. Other forms of treatment focus on attempting to control the symptoms of ALS and improving the quality of life for patients. The patient and family can work with caregivers to design a care plan that includes medical care as well as physical, occupational, and speech therapy, and any equipment and supplies needed to keep the patient as comfortable and mobile as possible. Throughout the progression of the disease, patients and their families will have to make several difficult decisions. As facial and throat muscle control deteriorates, making chewing and swallowing more difficult, a decision will have to be made about providing nutrition. Temporary nutritional support can be given through intravenous access, but a more permanent solution is typically needed and is achieved through some type of feeding tube. The option most commonly chosen is placement of a percutaneous endoscopic gastrostomy (PEG) tube. The tube is

surgically inserted through the abdominal wall and directly into the stomach, allowing for sizeable amounts of nutrition and liquids to be given at one time without posing a risk to the patient. Medications are also given through the feeding tubes. When the respiratory muscles begin to weaken, patients can choose to aid their breathing using devices that artificially inflate the lungs and provide necessary oxygenation such as a bi-level positive airway pressure (BIPAP) machine. ALS patients will eventually have to consider more permanent forms of mechanical ventilation such as respirators or a tracheostomy, in which a breathing tube is placed directly into

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the trachea through an opening made in the neck.

Ventilation devices can ease breathing

difficulties and may prolong survival but will not affect the progression of ALS, so it is important that patients and their families are fully informed before making these decisions. Amyotrophic Lateral Sclerosis is a very unkind disease, and is physically and emotionally devastating to the patients and their families. The full extent of its damage can only be understood by someone living with the disease, and the family members who see their fight and deterioration each day. The man I introduced at the beginning was my father. He developed bulbar-onset ALS and his disease progressed even more rapidly than expected. He fought the disease on his own terms, and never chose any mechanical support. Each case is different, and the plan of attack chosen will vary for every physician and every patient. Researchers are making new strides every day, and hopefully one day the causes will be discovered and a cure can be developed.