Amyotrophic Lateral Sclerosis (ALS)

Symptoms of ALS 

Muscle weakness is the major symptom of ALS. In early stages, the weakness may present itself as a problem with muscle endurance. Twenty percent of patients may experience a compromise in the ability to speak as the first symptom. A patient may experience a range of symptoms which become progressively worse over time:

• Muscle twitching in arms and legs
• Difficulty in walking
• Muscle weakness in legs, feet or ankles; weakness and clumsiness in hands.
• Hand weakness or clumsiness
• Slurring of speech or trouble swallowing
• Muscle cramps and twitching in arms, shoulders, and tongue
• Difficulty holding head up or keeping a good posture

Pain is not a recognized symptom of ALS, but some may occur.

ALS does not usually affect the senses, ability to think, sexual function and bowel or bladder control; it will, however, eventually eliminate the ability to control muscles responsible for moving, speaking, eating and breathing. For example, ALS may affect the respiratory system in several ways as the disease progresses:

• The disease can cause increased secretions in the airways of the lungs which may interfere with the ventilator phase of respiration; this will result in lower oxygen levels and higher levels of carbon dioxide, making the patient breathless and reducing energy levels.
• If ALS causes the mechanical phase of respiration to be degraded, a patient may experience an ineffective cough that can lead to an accumulation of secretions in the bronchial tubes. This accumulation, along with an increased occurrence of food or liquid aspiration, can foster growth of bacteria which can lead to pneumonia.

Causes of ALS 

The causes of ALS are unknown at present, but researchers are focusing on several possible theories, including gene mutations, overabundance of the neurotransmitter glutamate (which can be toxic to nerve cells), autoimmune response (in which the body’s immune system attacks normal cells) and the gradual accumulation of abnormal proteins in nerve cells.

ALS may be inherited in 5‒10 percent of cases (familial ALS), but the rest of the patients who contract the disease seem to do so at random (sporadic ALS). Most patients diagnosed with ALS do not have a history of ALS in any of their immediate family members.

• In the case of familial ALS, for 80 percent of cases, the gene mutation is not identified; only about 20 percent of people with this form of ALS possess an identifiable mutation on chromosome 21, a defect in the enzyme Cu/Zn superoxide dismutase (SOD1).
• In sporadic ALS, several theories have been proposed to explain the possible cause of motor neuron damage.
• The basis of the theory of excitotoxicity is that when the neurotransmitter glutamate is present in high concentrations, it can damage and destroy motor neurons; whether this is due to overproduction of the substance or an inability to reuptake is not known.
• Tissue studies of sporadic ALS patients have shown a higher concentration of altered proteins and greater production of free radicals from cell mitochondria than in tissues of non-ALS subjects. An increased concentration of these substances can damage all parts of a cell.
• Animal models have demonstrated that subjects with motor neuron conditions show early onset activation of the body’s immune system which can lead to inflammation in motor neurons.
• The role of neurotrophic hormones — proteins that promote growth and regeneration in neurons such as insulin-like growth factor-1 (IGF-1), ciliaryneurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF)  — is also being examined as a potential factor in the death of motor neurons.

Quite possibly, a "communal" process occurs in sporadic ALS that involves all these mechanisms. 

Several different forms of motor neuron disease similar to ALS have been described.

• Spinal muscular atrophy is a lower motor neuron inherited disorder that typically occurs during the first two decades of life; the defect is located on chromosome 5 but the specific abnormality is not defined.
• X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is a lower motor neuron disease linked to the X chromosome that occurs primarily in males and is characterized by limb weakness, speech and swallowing difficulties, enlargement of the breasts and testicular atrophy. Currently, it is not understood as to why this condition causes motor neuron loss.

For most patients with ALS, muscle weakness progresses over a three- to five-year period; a small number of people will see the same progression over a period as short as one year and 20 percent of patients may see the advancement of the disease take more than five years. The reasons for the variations are unknown and the course of the disease is difficult to predict on an individual basis.

One to two people out of every 100,000 will develop this disease a year. ALS affects men more than women in a 2:1 ratio, but after age 60, this rate evens out. The average age symptoms start to appear is between 53 and 57 years; about 80 percent of all cases start between the ages of 40‒70. ALS can occur in people of any race; the incidence of ALS is much higher in Guam, western New Guinea and select areas of the Kii peninsula of Japan.

Other factors that may increase the risk of developing the disease include smoking, exposure to lead and service in the military.

Diagnosis & Management of ALS >>