Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. ALS was first described in 1869 by the French neurologist Jean-Martin Charcot and hence is also known as Charcot disease; however, it gained popular recognition and its best-known eponym after the baseball player Lou Gehrig announced his diagnosis with the disease in 1939. ALS is also known as motor neurone disease (MND).
Amyotrophic Lateral Sclerosis, also known as Lou Gehrig disease, is an incapacitating disease of unknown cuase that results from degeneration of upper and lower motor neurons or of the cerebral cortex, brain stem, and spinal cord. This causes progressive loss of voluntary muscle contraction and functional capacity, accompanied by other lower motor neuron signs such as atrophy or fasciculations. ALS usually affects men between ages 40 and 70. It is invariably fatal, usually within 2 to 5 years of diagnosis, death usually results from a complication such as respiratory failure, aspiration pneumonia, or cardiopulmonary arrest.
The cause of ALS is unknown, although 5-10% of cases are familial. Some research is showing that ALS may share common biological mechanisms with Alzheimer disease, Parkinson disease, and other neurodegenerative diseases. Collaborative research is increasing.
In its classic form, ALS affects motor neurons at 2 or more levels supplying multiple regions of the body. It affects lower motor neurons that reside in the anterior horn of the spinal cord and in the brain stem; corticospinal upper motor neurons that reside in the precentral gyrus; and, frequently, prefrontal motor neurons that are involved in planning or orchestrating the work of the upper and lower motor neurons.
Loss of lower motor neurons leads to progressive muscle weakness and wasting (atrophy). Loss of corticospinal upper motor neurons may produce stiffness (spasticity), abnormally active reflexes, and pathological reflexes.
Loss of prefrontal neurons may result in special forms of cognitive impairment that include, most commonly, executive dysfunction but may also include an altered awareness of social implications of an individual’s circumstances and, consequently, maladaptive social behaviors. In its fully expressed forms, the prefrontal dysfunction meets established criteria for frontotemporal dementia.
The term classic amyotrophic lateral sclerosis is reserved for the form of disease that involves upper and lower motor neurons. The classic form of sporadic ALS usually starts as dysfunction or weakness in one part of the body and spreads gradually within that part and then to the rest of the body. Ventilatory failure results in death, on average, 3 years after the onset of focal weakness.
If only lower motor neurons are involved, the disease is called progressive muscular atrophy (PMA). Although many patients with PMA have a course indistinguishable from that of classic ALS, others have a course that may be longer.
When only upper motor neurons are involved, the disease is called primary lateral sclerosis (PLS). The course of PLS differs from that of ALS and is usually measured in decades. Rarely, the disease is restricted to bulbar muscles, in which case it is called progressive bulbar palsy (PBP). In most patients who present with initial involvement of bulbar muscles, the disease evolves to classic ALS.
Worldwide, ALS occurs sporadically in 90-95% of cases and with Mendelian patterns of heredity (familial ALS) in 5-10% of cases. Most familial ALS is inherited in an autosomal dominant pattern.
The diagnosis of ALS is primarily clinical. Electrodiagnostic testing contributes to the diagnostic accuracy.
ALS is a fatal disease, with median survival of 3-5 years. Aspiration pneumonia and medical complications of immobility contribute to morbidity in patients with ALS. Although ALS is incurable, there are treatments that can prolong meaningful quality of life; therefore, diagnosis is important to patients and families.
Assessment:
1. Progressive weakness and wasting of muscles of arms, trunk, and legs
2. Muscle fasciculations and spasticity
3. Tachypnea, hypopnea, restlessness, poor sleep, and excessive fatigue caused by hypoxia from respiratory weakness.
4. Cranial nerve dysfunction, particularly gag reflex and swallowing difficulty, as well as nasal and unintelligible speech.
What causes ALS?
The cause of ALS is not known, and scientists do not yet know why ALS strikes some people and not others. An important step toward answering that question came in 1993 when scientists supported by the National Institute of Neurological Disorders and Stroke (NINDS) discovered that mutations in the gene that produces the SOD1 enzyme were associated with some cases of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by free radicals. Free radicals are highly reactive molecules produced by cells during normal metabolism. If not neutralized, free radicals can accumulate and cause random damage to the DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. In support of this, animal studies have shown that motor neuron degeneration and deficits in motor function accompany the presence of the SOD1 mutation.
Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid. Laboratory studies have demonstrated that neurons begin to die off when they are exposed over long periods to excessive amounts of glutamate. Now, scientists are trying to understand what mechanisms lead to a buildup of unneeded glutamate in the spinal fluid and how this imbalance could contribute to the development of ALS.
Autoimmune responses—which occur when the body's immune system attacks normal cells—have been suggested as one possible cause for motor neuron degeneration in ALS. Some scientists theorize that antibodies may directly or indirectly impair the function of motor neurons, interfering with the transmission of signals between the brain and muscles.
In searching for the cause of ALS, researchers have also studied environmental factors such as exposure to toxic or infectious agents. Other research has examined the possible role of dietary deficiency or trauma. However, as of yet, there is insufficient evidence to implicate these factors as causes of ALS.
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