Lou Gehrig’s disease: I thought I would cover this, since three of my four Bush League teams are in his league.
Overview
Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, is a progressive neuromuscular disease that weakens and eventually destroys motor neurons (components of the nervous system that connect the brain with the skeletal muscles). Skeletal muscles are involved with voluntary movements, such as walking and talking. The motor neurons transmit the command to move from the brain to the skeletal muscles, which respond by contracting.
A person with ALS usually presents with problems in dexterity or gait resulting from muscle weakness, or with difficulty speaking or swallowing. Sphincter control, sensory function, intellectual ability, and skin integrity are preserved. Patients become paralyzed and often require ventilation and surgery to provide a new opening in the stomach (gastrostomy). Loss of respiratory function is ultimately the cause of death.
Incidence and Prevalence
Approximately 30,000 patients in the United States currently have ALS. The disease has no racial, socioeconomic, or ethnic boundaries. The life expectancy of ALS patients is usually 3 to 5 years after diagnosis. ALS is most commonly diagnosed in middle age and affects men more often than women.
Risk Factors
Risk factors include an inherited genetic defect, which accounts for 5–10% of cases of familial ALS (FALS) in the United States. FALS is linked to a genetic defect on chromosome 21. This gene codes for an enzyme called superoxide dismutase (SOD), an antioxidant that protects motor neurons from free radical damage (i.e., molecules introduced to the body, or produced by body processes that interact and cause cellular damage). More than 60 different mutations that cause SOD to lose its antioxidant properties have been found. However, only 40% of familial ALS cases are linked to SOD mutations, so there may be other unknown genetic defects involved.
In the United States, 90–95% of ALS cases are sporadic. Sporadic ALS appears to be increasing worldwide. The causes are not clear, yet some evidence suggests that the immune system may be involved. Excessive levels of glutamate can overstimulate motor neurons and cause them to die. Glutamate is one of the most important neurotransmitters for healthy brain function. Neurotransmitters are chemicals that transmit signals from one nerve to another.
In Guamanian ALS, a dietary neurotoxin is the risk factor. The suspected neurotoxin is an amino acid (BMAA) found in the seed of the cycad Cyas cirinalis, a tropical plant found in Guam, which was used to make flour and was a major dietary component during the 1950s and the early 1960s, when this type of ALS had an exceptionally high incidence.
Causes
The cause of ALS is not completely understood. Researchers and physicians suspect viruses, neurotoxins (especially in Guamanian ALS), heavy metals, DNA defects (especially in familial ALS), immune system abnormalities, and enzyme abnormalities.
Signs and Symptoms
Once a motor neuron degenerates completely, the muscle that it controls no longer receives impulses from the brain. Approximately 60% of ALS patients experience muscle weakness and stiffness as the initial symptom. Usually the first muscles affected are those in the arms and legs. Walking or climbing stairs may be difficult. The patient may drop things, fall, experience muscle cramps, and laugh or cry uncontrollably. The arms and legs may feel especially tired. If the hands are affected, the patient may have difficulty picking up small objects or turning keys. Speech problems, such as slurring, hoarseness, or decreased volume may also occur.
Signs and symptoms include the following:
- Absence of spinal reflexes (areflexia)
- Loss of muscle tone (hypotonia)
- Muscle twitching (fasciculations)
- Muscle wasting (atrophy)
The signs that the upper motor neurons are affected include the following:
- Excessive salivation
- Extension of the big toe and abduction of the rest of the toes in response to lightly stroking the sole of the foot (Babinski's sign)
- Reduced muscle tone, or hypotonia, and rigidity (spasticity)
- Hyperactive tendon reflexes
- Impaired speech (dysarthria)
- Impaired swallowing (dysphagia)
- Rapidly alternating muscle contractions and relaxations (clonus)
As symptoms progressively worsen, the patient's muscles atrophy causing spasticity, stiffness, abnormal movements, and alterations in gait and manual dexterity. Twitching may occur in the tongue and in affected limbs. The patient may experience muscle pain and muscle cramps. Some patients experience more difficulty swallowing saliva and liquids than solid food. Excessive salivation and difficulty swallowing may cause drooling. When respiratory muscles weaken, the patient may require a ventilator.
ALS patients often experience fear, anxiety, and depression.
DiagnosisALS is difficult to diagnose because the symptoms are similar to those of other neuromuscular disorders, many of which are treatable. The diagnosis is usually based on a complete neurological examination and clinical tests.
The neurological exam usually shows evidence of muscle weakness (localized or widespread, depending on the extent of the disease). The exam also reveals muscle atrophy. The muscles may be so stiff that when the neurologist moves them, they continue to move abnormally afterward. When the neurologist tests the "knee jerk" reaction, the movement is abnormally quick.
Because ALS affects the skeletal, voluntary muscles, the neurological exam does not reveal abnormalities in the sensory reflexes (i.e., vision, hearing, taste, smell, touch, or bowel and bladder control).
TestsNerve conduction velocity (NCV) and electromyography (EMG) help diagnose nerve and muscle disorders. These tests, which can be used in combination, are often referred to as
EMG/NCV studies. NCV is administered before EMG and measures the speed at which nerves transmit electrical signals.
During NCV, electrodes are placed on the skin over a nerve that supplies a specific muscle or muscle group. A mild, brief electrical stimulus is delivered through the electrode and the response of the muscle is detected, amplified, and displayed. The strength of the signal is also measured. Neurological conditions can cause the NCV to slow down or to be slower on one side of the body. The strength of the response also provides clues to help with diagnosis and to determine the extent of the disease.
EMG measures nerve impulses within the muscles. Tiny electrodes are placed in the muscles in the arms and legs and the electronic responses are observed using an instrument that displays movement of an electric current (oscilloscope). As muscles contract, they emit a weak electrical signal that can be detected, amplified, and tracked, providing information about how well the muscles are working. These responses are abnormal in cases of ALS.
Tests may be performed to rule out other neurological disorders.
Magnetic resonance imaging (MRI scan) may be used to rule out spinal cord disease. Blood tests may be done to detect the presence of heavy metals such as lead in the blood. Laboratory tests may detect abnormal proteins or hormone levels associated with other neurological diseases. A lumbar puncture or spinal tap may be performed to analyze the cerebrospinal fluid for genetic abnormalities (e.g., viral, autoimmune, neurotoxic).
TreatmentThere is no cure for ALS. Treatment focuses on relieving symptoms and maintaining an optimal quality of life. Treatment is based on individual therapy and the continual adaptation of medications. Riluzole (Rilutek®) is one of the few drugs effective against ALS and may prevent progression and prolong life for a few months or so. Riluzole decreases the release of glutamate. Side effects include the following:
- Dizziness
- Elevated liver enzymes
- Reduced leukocytes in the blood (granulocytopenia)
- Weakness (asthenia)
Baclofen (Lioresol®) or tizanadine (Zanaflex®) may relieve spasticity. Side effects include increased weakness, sedation, and dizziness. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen may relieve general discomfort. Due to potentially severe gastrointestinal and cardiovascular side effects, NSAIDs should only be used as instructed. Tramadol (Ultram®) is often prescribed for pain relief.
Physical therapy is an important part of treatment and helps to relieve cramping and muscular pain. Passive stretching helps to avoid permanent contraction of muscles (contractures) that may cause joint problems.
Other therapies, such as occupational therapy and speech therapy, are also used in treatment. ALS patients require a diet of high-energy foods that are easy to swallow. Patients may benefit from a nutritionist. If the patient is not able to maintain adequate nutrition, a percutaneous endoscopic gastrostomy (PEG), or feeding tube, is usually inserted.
Some ALS patients may also need pulmonary consultants and respiratory therapists to assist breathing. Fewer than 5% of patients use long-term ventilation support.
Depression is very common among ALS patients. Antidepressant medication and counseling can help patients and their families cope.
PrognosisALS is a terminal illness. Fifty percent of patients die within 3 years of diagnosis; 20% live 5 years; and 10% live 10 years. Hospice care can provide comfort and dignity to patients and their loved ones.
