Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease)is a progressive disease in which patients’ muscles weakenand shrivel away. The disease takes patients’ lives onthe average 3 years after the first symptoms of weakness appear.Most often, this happens when the breathing muscles are unableto do their job. Sometimes patients choose to extend their livesby being connected to a breathing machine. The cause of mostcases of ALS is unknown. A small number of cases occur withinfamilies, but over 90% occur randomly.1 Some previous studieshave suggested that ethnicity might be one risk factor thatdetermines who develops ALS, but others have suggested thatthis is not important. In this issue of Neurology, Cronin andcolleagues2 explain what is known about the role of ethnic originas a risk factor for development of ALS.
The authors reviewed studies published in a 40-year period (1966through 2006) that evaluated how often ALS appears in differentgeographic areas and different ethnic groups. The authors found61 papers, but only 45 had good information on how often thedisease is seen in different areas, including numbers called"incidence" and "prevalence."
"Incidence" is the number of new patients who develop diseaseeach year divided by the number of people in the group (population)being studied. For people living in the United States and Europe,the incidence of ALS is approximately 2 per 100,000 people peryear. However, the incidence of ALS increases as we get older,and for the 45- to 75-year-old age group, it is closer to 5per 100,000 people per year.
"Prevalence" is how many people in a group (population) havethe disease at any given point in time divided by the numberof people in the group. Unfortunately, there were very few studiesfrom outside Europe and North America (only eight), and thequality of the studies was uneven. Most of the high-qualitystudies were conducted in Europe and North America (except forone in Japan and one in Uruguay). Many of the studies did nothave enough information to compare results with other studies.This limits the ability to perform the comparisons needed toanswer the authors’ main question.
The main finding of the authors is that incidence appears tobe lower among African, Asian, and Hispanic populations comparedwith Caucasians. However, the authors are not sure if that isa correct conclusion because of the limitations in the data.The main concern is whether all patients who developed ALS hadthe same chance of being counted, regardless of when or wherethe study was done or of the patients’ ethnic origin.The authors are proposing that a large, well-designed studyconducted in a racially mixed population might be needed toget a better answer to this question.
This is not easy to do. For example, if there were only twoethnic groups and one was four times more common than the other,then about 10 million individuals would need to be followedfor 5 years to be able to detect with reasonable certainty a25% difference between the groups in incidence of ALS. The onlyrealistic way that this might be done in the United States isthrough a thorough effort across several states that have aracially diverse population. Alternatively, an effort acrossmany nations could be done, using methods that would ensurethat all patients who developed ALS in the populations studiedhad an equal chance of coming to the attention of the researchers.
If ethnic differences in the risk of developing ALS were confirmed,this might provide clues as to what causes the disease and givefocus to more research. Ethnic differences in ALS occurrencemay suggest that there are different risk factors (environmentalor genetic) across different ethnic groups. Ethnic differencesin health may be due to socioeconomic, cultural, and religiousfactors.3 These factors may determine differences in lifestyles.Some behaviors could be changed, such as smoking1 or diet. Theuse of specific toxic or poisonous substances may also leadto an increased frequency of a disease in a specific ethnicgroup. On the other hand, differences in disease incidence maybe due to the presence of different sets of genes in differentethnic groups. It is important to find as many clues as possibleto identify what places people at risk for developing ALS becausewe do not know what causes the most common form of the disease.Careful studies in different ethnic groups might give us cluesto both environmental and genetic risk factors for ALS.
Patient Page — About ALS
About ALS
Amyotrophic lateral sclerosis (ALS) is a disease in which thepatient’s muscles gradually weaken and deteriorate,1 andthis leads to death. ALS usually begins in one region of thebody and spreads to adjacent regions until the entire body isinvolved. As the muscles waste away, they often become stiff(spastic). The disease is different in each patient. ALS alsoaffects the muscles responsible for speaking, swallowing, andbreathing. Unless ALS patients choose to receive permanent mechanicalbreathing support, patients die when the muscles used for breathingno longer work. This happens on the average 3 years after theappearance of the first signs of weakness.
The reason why muscles shrivel away and stiffen in ALS is thatthere is gradual loss of the two types of nerve cells knownas motor neurons, which make the muscles work (figure). Thefirst type, or lower motor neurons, are found in two areas:in the spinal cord, where they are connected directly to thelimb and spinal muscles, including the breathing muscles; andin the lower part of the brain (brainstem), where they are connecteddirectly to muscles of the face, mouth, and throat, includingmuscles that control speech and swallowing. The muscles needthe connection to lower motor neurons, not just to be able todo their job but also to live. Therefore, as lower motor neuronsdie and the muscles are no longer connected to those lower motorneurons, they also weaken, atrophy, and die. The second typeof motor neuron, the upper motor neuron, is found in the brain.It is connected directly to the lower motor neurons and tellsthem what to do. As upper motor neurons die, they exert lesscontrol over the lower motor neurons; this results in the tendencyof the muscles to stiffen. Although ALS presents as a diseaseof muscle loss, it is caused by the loss of the nerves thatare connected to those muscles. For this reason, another namefor ALS is "motor neuron disease."
Figure. Diagram of a motor neuron (left) and of the locations and connections of representative upper and lower motor neurons (right). Figure drawn by Lee Lesneski, RN; reproduced from Armon.1
ALS affects adults, and the risk of developing ALS increasesas one gets older. Men are affected more frequently than women.Of every 1 million adults age 18 or older, between 30 and 40will develop ALS each year. It is estimated that in 2002, approximately1 in every 350 men or 450 women who died in the United Statesdied of ALS.2 About 1 in 20 ALS patients have or have had bloodrelatives with the disease, and this is referred to as the "familial"form of ALS. Over 90% are considered to have the "sporadic"or randomly occurring form of the disease. Its causes are notknown. Common symptoms of the disease include weakness, musclecramps, difficulties with speech and swallowing, unsteadiness,stiffness (spasticity), twitching muscles, loss of muscle bulk(atrophy), foot drop, and breathing difficulties. In addition,patients may experience depression or periods of laughing andcrying that are not under their control and seem out of proportionto or unconnected to the underlying emotions. There may be changesin the ability to think, usually with trouble in planning andsequencing abilities, and, less commonly, seeming to not careabout the impact of the disease on oneself and one’s lovedones. Memory tends not to be affected.
As the precise causes of ALS are unknown, little can be doneto prevent it. Smoking is the best established risk factor forthe disease and should be avoided. It is also a major risk factorfor the leading causes of death in the developed world: heartdisease, some forms of cancer, and stroke.
Treatment of ALS is accomplished best using a team approach.There is one approved medication for the disease—riluzole—thathas been shown to extend life by 2 to 3 months. Education aboutthe disease helps patients and their families to feel more incontrol as the disease progresses. There are many sources ofgood information for patients1,2–5 and many centers dedicatedto caring for them throughout the world.6
The text of this "Patient Page—About ALS" is modifiedfrom Armon.1
Armon C. An evidence-based medicine approach to the evaluation of the role of exogenous risk factors in sporadic amyotrophic lateral sclerosis. Neuroepidemiology 2003;22:217–228.[Medline]
Cronin S, Hardiman O, Traynor BJ. Ethnic variation in the incidence of ALS: a systematic review. Neurology 2007;68:1002–1007.[Abstract/Free Full Text]
Pearce N, Foliaki S, Sporle A, Cunningham C. Genetics, race, ethnicity, and health. Br Med J 2004;328:1070–1072.[Free Full Text]
Armon C. ALS 1996 and beyond: new hopes and challenges. A manual for patients, families, and friends, 3rd ed. English and Spanish versions. 2000. www.llu.edu/llumc/neurosciences/als/
Armon C. Sports and trauma in amyotrophic lateral sclerosis revisited. J Neurol Sci. Special Issue on Environmental Neurology, Román G, editor. In press.
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