Amyotrophic Lateral Sclerosis

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What is amyotrophic lateral sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS, commonly called “Lou Gehrig's disease” in the US) is the most common motor neuron disease in adults. Motor neuron diseases are neurodegenerative diseases that cause selective loss of the nerve cells that connect the brain to the muscles. ALS affects both upper and lower motor neurons throughout the brain and spinal cord. Other motor neuron diseases may affect only the upper motor neurons, only the lower motor neurons or a restricted selection of neurons.

Based on US population studies, over 5600 people in the US are diagnosed with ALS each year (approximately 15 new cases a day). It is estimated that as many as 30,000 Americans have the disease at any given time. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. However, cases of the disease do occur in persons in their twenties and thirties. ALS is 20% more common in men than in women, however with increasing age, the incidence of ALS is more equal between men and women.

Genetics of ALS

The genetic mechanisms that cause ALS are only partially understood. The first gene that was discovered to cause ALS is called the SOD1 gene. This mutation is believed to make a defective protein that is toxic to motor nerve cells. The SOD1 mutation, however, accounts for only 1-2% of ALS cases, or 20% of the familial (inherited) cases. More recently, another gene called FUS was found to be responsible for approximately 3-5% of ALS cases. A much less common cause for ALS is a mutation in a gene related to FUS called TDP43.

While estimates vary, it is now believed that approximately 20% of ALS patients also have the signs and symptoms of frontotemporal dementia. As a result, patients may lack the ability to fully understand the meaning of their illness, they may make poor decisions about their clinical care, or they may become agitated and difficult for caregivers who are trying to help them. Other patients may have trouble understanding language or communicating, which is a separate problem from the articulation problems that come with ALS. Some ALS patients have had changes in their behavior or psychiatric problems for years before they developed ALS, and only until a full neuropsychological exam is completed does the family understand that an FTD disease had begun several years before. Researchers have found that in addition to those patients who have a diagnosis of FTLD, upwards of 50% of ALS patients have mild changes in their ability to concentrate, focus on multiple ideas or actions at one time, or make complex judgments, called ‘executive functioning’.

Signs & symptoms of ALS

The primary symptom of lower motor neuron disease is weakness. The weakness usually begins in one hand, one foot, or the tongue. As weakness becomes more severe, the involved muscles become smaller, and weakness spreads to other muscles. Cramping and twitching of muscles are common; however, these symptoms are also common in healthy people. Clinicians typically use electromyography (EMG) to diagnose lower motor neuron disease.

The primary symptoms of upper motor neuron disease are stiffness, slowness and clumsiness of movement. The symptoms usually begin in one limb or in the mouth or throat, later spreading to other parts of the body. There are no standard laboratory tests for upper motor neuron disease, but spasticity (a specific type of stiffness), abnormally brisk tendon reflexes, Babinski's sign and diminished fine motor coordination are seen as diagnostic signs on examination.

Progression of ALS

The earliest symptoms of amyotrophic lateral sclerosis may be so slight that they are frequently overlooked. All patients with ALS will experience progressive muscle weakness and paralysis, but not all people will share the same symptoms or the same patterns of progression. From the time of diagnosis, a patient with ALS typically survives three to five years.

Treatment of ALS

Physicians have limited choices for treating ALS. Studies suggest that patients' length of survival and quality of life are enhanced by night-time breathing assistance early in the course of the disease and by aggressive application of alternate feeding options to assure good nutrition once swallowing becomes difficult. At this time, Riluzole® is the only drug that has been approved by the FDA for treatment of ALS. In clinical trials, Riluzole® has shown a slight benefit in modestly increasing survival time. Patients with co-morbid FTLD and ALS more often have difficulty following treatment recommendations, perhaps because agitation, poor insight and cognitive changes result in a refusal to comply with physician’s recommendations. As a result, life span is sometimes shortened in patients with both diseases. Specific medicines have been found to be helpful to treat the agitation, apathy and depression commonly seen in FTLD.

Medications to avoid

Medications that might influence muscle strength or swallowing should be avoided, particularly drugs that block dopamine in the brain.

Resources for ALS

Caregiving for any patient with a debilitating illness can be both fulfilling and exhausting. ALS patients’ needs change rapidly as the disease progresses, and impaired communication can make caregiving more difficult. Caregivers for ALS patients are also at increased risk for depression and stress because of the emotional and economic stress of coping with an illness that requires expensive equipment and will result in losing their loved one.

When patients have both FTD and ALS, they often have poor insight into their ALS symptoms, and as a result may disagree with family about clinical changes, treatment recommendations and the need for necessary equipment. They sometimes have trouble using a communication device or making decisions regarding PEG and BiPAP, which are significant life-sustaining measures. All of these problems confound an already very difficult disease for families and health care providers.

November 15, 2010