Amyotrophic Lateral Sclerosis

(ALS, sometimes called Lou Gehrig's Disease, or Maladie de Charcot) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. As one of the motor neuron diseases, the disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, develop fasciculations (twitches) because of denervation, and eventually atrophy due to that denervation. The patient may ultimately lose the ability to initiate and control all voluntary movement except of the eyes.

Cognitive function is generally spared except in certain situations such as when ALS is associated with frontotemporal dementia. However there are reports of more subtle cognitive changes of the frontotemporal type in many patients when detailed neuropsychological testing is employed. Sensory nerves and the autonomic nervous system, which controls functions like sweating, generally remain functional.

Epidemiology, causes and risk factors

ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. One to 2 people per 100,000 develop ALS each year ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women.

"Familial ALS" accounts for approximately 5%-10% of all ALS cases and is caused by genetic factors. Of these approximately 1 in 10 are linked to a mutation in copper/zincSuperoxide dismutase (SOD1), an enzyme responsible for scavenging free radicals. As an antisense drug trial using a small interfering RNA molecule (siRNA) that inhibits the production of this mutant SOD1 protein.

Although the incidence of ALS is thought to be consistently around 1-2 per 100,000 people per year, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS, although this seems to be declining in recent decades. The largest is the area of Guam inhabited by the Chamorro people who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of ALS, Parkinsonism, and dementia. Two more areas of increased incidence are the Kii peninsula of Japan and West Papua.

Although there have been reports of several "clusters" including three American football players from the San Francisco 49ers, three soccer-playing friends in the south of England, and reports of conjugal (husband and wife) cases in the south of France, these are statistically plausible chance events. Although many authors consider ALS to be caused by a combination of genetic and environmental risk factors, so far the latter have not been firmly identified, other than a higher risk with increasing age.

Cause and risk factors

Scientists have not found a definitive cause for ALS and the onset of the disease has been linked to a several factors, including: a virus; exposure to neurotoxins or heavy metals; DNA defects; immune system abnormalities; and enzyme abnormalities. There is a known hereditary factor in familial ALS (FALS); however, there is no known hereditary component in the 90-95% cases diagnosed as sporadic ALS. An inherited genetic defect linked to a defect on chromosome 21 is believed to cause approximately 40% of familial cases of ALS. This mutation is believed to be autosomal dominant. The children of those diagnosed with familial ALS have a higher risk factor for developing the disease; however, those who have close family members diagnosed with sporadic ALS have no greater a risk factor than the general population.

Some causative factors have been suggested for the increased incidence in the western Pacific. Prolonged exposure to a dietary neurotoxin is the suspected risk factor in Guam; the neurotoxin is a compound found in the seed of the cycad Cycas circinalis, a tropical plant found in Guam, which was used in the human food supply during the 1950s and early 1960s.

According to The ALS Association, military veterans are at an increased risk of contracting ALS. In its report ALS in the Military, the group pointed to an almost 60% greater chance of the disease in military veterans than the general population. For Gulf War vet's, the chance is seen as twice that of the general population in a joint study by the Veteran's Affairs Administration and the DOD.

Symptoms

Initial Symptoms

The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. These general complaints then develop into more obvious weakness or atrophy that may cause a physician to suspect ALS.

The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people experience "limb onset" ALS. In some of these cases, symptoms initially affect one of the legs, and patients experience awkwardness when walking or running or they notice that they are tripping or stumbling more often. Other limb onset patients first see the effects of the disease on a hand or arm as they experience difficulty with simple tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock.

About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly. Speech becomes garbled and slurred. Nasality and loss of volume are frequently the first symptoms. Difficulty swallowing, and loss of tongue mobility follow. Eventually total loss of speech and the inability to protect the airway when swallowing are experienced.

Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign (the large toe extends upward as the sole of the foot is stimulated) also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). Around 15–45% of patients experience pseudobulbar affect, also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling.

To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.