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Amyotrophic Lateral Sclerosis
#1
AMYOTROPHIC LATERAL SCLEROSIS


Edit by Author, 1/15/2013


Some of the source links below are now dead. I was only allowed


to take one third of the original content. And leave links.


I give you permission to use one third also. Or search out the


videos first and and take them from there
.




http://www.youtube.com/watch?v=Dp4q8YNF9o4

[Image: alsnerves.gif]

What Types of Nerves Make Your Body Work Properly?
(from Living with ALS, Manual 1: What's It All About?)

The body has many kinds of nerves. There are those involved in the process of thinking, memory, and of detecting sensations (such as hot/cold, sharp/dull), and others for vision, hearing, and other bodily functions. The nerves that are affected when you have ALS are the motor neurons that provide voluntary movements and muscle power. Examples of voluntary movements are your making the effort to reach for the phone or step off a curb; these actions are controlled by the muscles in the arms and legs.

The heart and the digestive system are also made of muscle but a different kind, and their movements are not under voluntary control. When your heart beats or a meal is digested, it all happens automatically. Therefore, the heart and digestive system are not involved in ALS. Breathing also may seem to be involuntary. Remember, though, while you cannot stop your heart, you can hold your breath - so be aware that ALS may eventually have an impact on breathing.

Although the cause of ALS is not completely understood, the recent years have brought a wealth of new scientific understanding regarding the physiology of this disease.

Source





Marijuana's Potential Exciting Researchers in Treatment of ALS, Parkinson's Disease


A Legal Mood Lifter: Researchers are investigating a new antidepressant and pain reliever that works like cannabis (marijuana), without the illegal side effects.

A decade ago, when Daniele Piomelli went to scientific conferences, he was often the only researcher studying cannabinoids, the class of chemicals that give marijuana users a high. His work often drew snickers and jokes, but no more.

At the annual Society for Neuroscience conference recently, scientists here delivered almost 200 papers on the subject.

Why the attention? Many scientists believe cannabis-like drugs might be able to treat a wide range of diseases, far beyond the nausea and chronic pain typically treated with medical cannabis. Researchers here presented tantalizing evidence that cannabinoid drugs can help treat amyotrophic lateral sclerosis, known as ALS or Lou Gehrig's disease, Parkinson's disease and obesity.


Other researchers are studying whether the compounds can help victims of stroke and multiple sclerosis.

Although the chemicals work on the same area of the nervous system, the new drugs are much more refined and targeted than cannabis, with few of its side effects.

"Cannabinoids have a lot of pharmaceutical potential," said Piomelli, a neuroscientist at the University of California at Irvine.

"A lot of people are very excited"

Although the federal government opposes the use of medical marijuana, it generally doesn't restrict cannabinoid research, most of which doesn't involve the cannabis plant itself. Scientists who use Marinol, a legal but tightly regulated marijuana-like drug, do need government permission.

Because the cannabinoid system wasn't discovered until the late 1980s, decades after serotonin, dopamine and other neurotransmitters, researchers still know relatively little about how it works. Like all neurotransmitter networks, the cannabinoid system consists of a series of chemical pathways through the brain and nervous system.

Cannabis produces its effects by activating this pathway, primarily through the effects of tetrahydrocannabinol, or THC, the drug's main active ingredient.

Over the past decade, researchers have been following these abundant trails to determine their real purpose.

"You don't have them there to get stoned. So, there must be internal reasons," said Andrea Giuffrida, a neuroscientist at the University of Texas Health Sciences Center in San Antonio.

Researchers have learned that endogenous cannabinoids, internal brain chemicals that activate the system, play a role in tissue protection, immunity and inflammation, among other functions. The cannabinoid system also appears to exert wide influence, modulating the release of dopamine, serotonin and other neurotransmitters.

Giuffrida and others believe cannabinoids can treat degenerative disorders such as Parkinson's disease and ALS.

At the conference, Giuffrida announced that a cannabinoid drug wards off Parkinson's-like effects in mice.

The disorder, which afflicts more than 1 million Americans, destroys neurons in a key part of the brain, causing patients to lose control over movement.

Giuffrida, with colleagues David Price and James Roberts, injected mice with a chemical called MPTP, which mimics Parkinson's damage.

When some of the animals subsequently received a drug that blocks cannabinoid receptors, their nerve cells suffered far less damage than did the cells of the other mice.

This was the first demonstration that a cannabinoid drug can have this effect. Although he is not sure how the anti-cannabinoid compound works, Giuffrida suspects it protects neurons by reducing inflammation, a key component in Parkinson's.

Cannabinoids might also slow down ALS, which destroys neurons that control muscles until victims become paralyzed, unable to breathe on their own.

Neuroscientist Mary Abood first became interested in cannabinoids after hearing about ALS patients who got some relief from smoking cannabis. So she began animal experiments at the California Pacific Medical Center in San Francisco.

In her study, mice with a variant of ALS were given a combination of THC and cannabidiol, another compound found in cannabis.

Both substances are cannabinoid agonists, chemicals that activate the cannabinoid system. Abood measured the course of the ailment by testing how long the mice could stand on a rod that was slowly rotating.

The treatment delayed disease progression by more than seven days and extended survival by six days.

In human terms, this would amount to about three years. That's a significant improvement over the only existing ALS drug, riluzole, which extends life by two months.

"I was very excited when I got my initial results," Abood said.

Also at the conference, researchers at the Institute of Neurology in London announced results that corroborated her findings. Cannabinoids have also helped some human ALS patients in one small trial, and Abood is trying to get funding for a larger one.

If cannabinoids can shield human neurons from harm, researchers say, they might prove useful against other neurological diseases, including mental illness.

Scientists are looking at whether cannabinoids can treat multiple sclerosis, epilepsy and Huntington's disease, while Giuffrida is beginning a study of their effect on schizophrenia.

Advocates of medical cannabis have long argued that the drug can be useful for treating many conditions, particularly chronic pain, nausea and glaucoma (in the latter, cannabis works by temporarily decreasing pressure around the eye).

Although they don't dispute this view, most researchers believe there are better, more precise ways to stimulate the cannabinoid system.

They believe cannabis has too many negatives to be a truly effective drug, with side effects that include memory problems, decreased immunity and possibly addiction. (Some researchers dispute this "addictive" claim.)

Cannabis has another drawback. From a scientific standpoint, Giuffrida says, it's "a very dirty drug." It contains more than 300 compounds, 60 of which affect the cannabinoid system. Scientists don't understand what most of these substances do or how they work together. This complexity makes it hard for researchers to pinpoint cannabis' effects.

One cannabinoid, Marinol, is available legally. The compound, which contains THC in a pill form, is usually prescribed for nausea and for appetite loss among AIDS patients. But Marinol has the same psychoactive effects as cannabis.

"So the key", Piomelli says, "is getting the effects without the side effects."

To that end, Piomelli has developed a compound called URB597, which doesn't flood the body with cannabinoids, as Marinol and cannabis do.

Instead, it slows the breakdown of the cannabinoids in the system. He thinks the drug may help treat pain, anxiety and even depression without making patients stoned and forgetful. He and others are testing it on animals.

SOURCE
http://www.illinoisn...ent/view/600/1/


http://www.youtube.com/watch?v=-qFSMXEYC3c




Survey of Cannabis Use in Patients with Amyotrophic Lateral Sclerosis

Dagmar Amtmann, PhD
Patrick Weydt, Md
Kurt L. Johnson, PhD
Mark P. Jensen, PhD
Gregory T. Carter, M.D.


Abstract

Cannabis (marijuana) has been proposed as treatment for a widening spectrum of medical condtions and has many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). This study is the first, anonymous survey of persons with ALS regarding the use of cannabis. There were 131 respondents, 13 of whom reported using cannabis in the last 12 months. Although the small number of people with ALS that reported using cannabis limits the interpretation of the survey findings, the results indicate that cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. Cannabis was reported ineffective in reducing difficulties with speech and swallowing, and sexual dysfuction. The longest relief was reported for depression (approximately two to three hours). Key words: pain, palliative care, cannabis, medicinal marijuana, amyotrophic lateral sclerosis.

Introduction

Amyotrophic lateral sclerosis (ALS), with an incident rate of five to seven per 100,000 population, is the most common form of adult motor neuron disease.1-3 ALS is a rapidly progerssive neuromuscular disease that destroys both upper and lower motor neurons, ultimately causing death, typically from respiratory failure. The vast majority of ALS is acquired and occurs sporadically. There is not yet a known cure for ALS. 4-6

ALS patients may present with any number of clinical symptoms, including weakness, spasticity, cachexia, dysarthria and drooling, and pain secondary to immobility, among others.7-8 Previous studies have reported both direct and theoretical applications for using cannabis to manage some of these ALS symptoms.9-11 Cannabis has easily observable clinical effects with rapid onset (e.g., analgesia, muscle relaxation, dry mouth). Moreover, some components of marijuana (not inhaled smoke) have been shown in laboratory studiues to have neuroprotective properties that may help prolong neuronal cell survival over extended time.12-16

Marijuana is a complex plant, containing over 400 chemicals.17 Approximately 60 are cannabinoids, chemically classified as 21 carbon terpenes.17,18 Among the most psychoactive of these is delta-9-tetrahydrocannabinol (THC).17,18 Because of this biochemical complexity, characterizing the clinical pharmacology of marijuana is difficult. The clinical pharmacology of marijuana containing high concentrations of THC may well differ from plant material containing small amounts of THC and higher amounts of the other cannabinoids. The bioavailability and pharmacokinetics of inhaled marijuana are also substantially different from those taken by ingestion. The cannabinoids are all lipid soluble compounds and are not soluble in water.19 Besides THC, which is the active ingredient in dronabinol, varying proportions of other cannabinoids, mainly cannabidiol (CBD) and cannabinol (CBN), are also present in marijuana and may modify the pharmacology of the THC as well as have distinct effects of their own. CBD is not psychoactive but has significant anticonvulsant and sedative pharmacologic properties and may interact with THC.20-21

The concentration of THC and other cannabinoids in marijuana varies greatly depending on growing conditions, plant genetics, and processing after harvest.21 In the usual mixture of leaves and stems distributed as marijuana, concentration of THC ranges from 0.3 percent to 4 percent by weight.21,22 However, specially grown and selected marijuana can contain 15 percent or more THC. Thus, one gram of marijuana might contain as little as three milligrams of THC or more than 150 mg.21 THC is a potent psychoactive drug, and large doses may produce mental and perceptual effects similar to hallucinogenic drugs.23,24 Despite this, THC and other cannabinoids have low toxicity, and lethal doses in humans have not been described.25,26

Despite risk for bronchitis, the main advantage of smoking is rapid onset of effect and easy dose titration. When marijuana is smoked, cannabinoids in the form of an aerosol in the inhaled smoke are rapidly absorbed and delivered to the brain, as would be expected of a highly lipid-soluble drug.27,28 However, smoking anything, including marijuana, carries health risks for the lungs and airway system. A healthier option is vaporization. Because the cannabinoids are volatile, they will vaproize at a temperature much lower than actual combustion.24 Heated air can be drawn through marijuana and the active compounds will vaporize, which can then be inhaled. This delivers the substance in a rapid manner that can be easily titrated to desired effect.29 Vaporization therefore removes most of the health hazards of smoking.27

The medicinal use of cannabis is better documented in multiple sclerosis (MS) than in other clinical conditions, although evidence tends to be anecdotal, and no controlled clinical trials of medicinal marujuana use in MS have been published.30-39 With respect to pain, the concominant use of cannabis with narcotics may be beneficial, because the cannabinoid receptor system appears to be discrete from that of opioids.40-45 In that regard, the antiemetic effect of cannabis may also help with the nausea sometimes associated with narcotic medications. Untoward effects of cannabis include potentially significant psychoactive properties, which may produce a sense of well-being or euphoria but can also induce anxiety, confusion, paranoia, and lethargy.46

To date there have not yet been any empirical studies to investigate the use of cannabis for medicinal purposes in ALS. The purpose of this survey was to gather preliminary data on the extent of use of cannabis among persons with ALS (PALS) and to learn which of the symptoms experienced by PALS are reported to be alleviated by the use of cannabis.

Metohdology

Participants in this survey were recruited from the ALS Digest (the Digest), an electronic discussion list published weekly to serve the worldwide ALS community, including patients, families, caregivers, and providers. The Digest serves as a forum for discussion of issues related to ALS and is not intended to provide medical advice on individual health matters. The Digest can be viewed at www.alslinks.com. Currently there are over 5,600 subscribers in 80 countries worldwide. However, the number of subscribers with ALS is not known. The editor is not a physician and the Digest is not peer reviewed. An e-mail invitation to participate was posted to the Digest four times over two months.

The survey was available online from January 6 through March 2, 2003, approximately eight consecutive weeks. Any subscriber with ALS was invited to participate on a voluntary and anonymous basis. The sponsoring institution human subjects review board approved the study protocol. A Web-based survey tool developed by the University of Washignton was used to collect responses. The tool uses SSL encryption for transferred data, and all identifying information was stored in a code translation table separate from the actual data to protect the privacy of respondents. The University of Washington human subjects review board has approved this tool for research purposes.

PALS who wanted to participate were given a Web site address that introduced the survey and provided a link to the survey site. The invitation to participate did not mention cannabis or marijuana, in order to discourage participation by individuals who do not have ALS but might otherwise be interested in promoting legalization of marijuana. The sruvey was titled "A survey of ALS Patients Who Use Alternative Therapies to Treat Symptoms."

It was presumed by the investigatiors that the diagnostic information provided by the survey participants was accurate (i.e., no medical records were reviewed to confirm their diagnosis). In addition to a series of questions related to the ALS symptoms, the use of cannabis, and its effectiveness in alleviating the symptoms of ALS, participants were also asked to provide demographic and diagnostic information. The survey was anonymous and it is therefore impossible to conclusively determine whether all respondents were individuals with ALS. However, the first six questions of the survey asked about how and when the respondent was diagnosed with ALS and specifically asked those who were not diagnosed with ALS by a physician to not fill out the survey. The authors carefully studied the demographic and diagnostic information provided by each respondent for completeness, consistency, and plausiblity. Records with the diagnostic information missing were excluded from the analysis. Many participants offered extensive information about other alternative therapies they use, and the general comments appeared to reflect experiences of individuals living with ALS.

Results

A total of 137 responses were received. Four responses were excluded because of duplicate submission (i.e. the same person inadvertently submitting more than one survey by hitting the submit key more than once) and two because of failure to complete most of the questions of the survey. Eletronic logs of all submissions were inspected for repeated entries from the same Internet protocol (IP) address. None were found. A total of 131 responses were retained for analysis.

The demographics of the sample are shown in Table 1. Seventy-five percent of the respondents were male and 90 percent were caucasian. The average age of participants was 54 years [standard deviation(sd)=11], with no significant difference between the genders [Mean(M) mean(m)=54 for=for males,=males, sd=12.5 m=53 females,=females,]. Eighty-four percent of the respondents were married or living with a significant other, 17 percent were employed (full time or part-time), 64 percent were unemployed or retired due to disability, and 18 percent were retired due to age. Respondents reported high levels of education, with only 13 percent with high school education or less and 62 percent with college education or higher. The time since ALS diagnosis ranged from one month to 24 years. The median time since diagnosis (i.e., duration) was three years, the mean duration was approximately four years (M=4.4, SD=4.0). About a half of the sample reported they used a wheelchair usually or always, and about 20 percent reported no restrictions in mobility. Eighty-one percent of the respondents filled out the survey independently while 19 percent reported that they required assistance from others. One-half of the participants were taking Riluzole. The majority of participants (69 percent) reported that they live in the Unted States, 8 percent in Canada, and 5 percent in Australia. Six percent of the participants live in Europe, while the rest (12 percent) of the respondents reported that they were from Africa, India, Israel, Brazil, Ecuador, Guatemala, or Argentina. Fifty-three participants (41 percent) reported drinking alcohol, 14 (11 percent) reported that they use tobacco, and four (3 percent) reported consuming both alcohol and tobacco.

Use of cannabis

Seventy-seven respondents (60 percent) reported that they never used cannabis, and 41 (31 percent) used cannabis in teenage or college years only. Thirteen respondents (10 percent) reported using cannabis in the last 12 months, and their demographics are outlined in Table 2.

Those who reported using cannabis in the last 12 months were all male and all lived in the US. Ten of those who reported using cannabis in the last 12 months also responded affirmatively to the question that asked about the use of cannabis during the teenage, college, and adult years. All of those who reported using cannabis in the last 12 months also reported that they used cannabis at some point in their lives before they were diagnosed with ALS. Six of the cannabis users reported that they lived in a state where medical cannabis is legal, and four lived in a state where medical cannabis is illegal. The remaining three respondents were not sure whteher medical cannabis was legal in their state. There were no statistcally significant differences between the cannabis users and non-users (see Table 2) on any demographic variable (age, marital status, employment status, education level, time since diagnosis, mobility status).

None of those who reported using cannabis in the past 12 months reported tobacco use, but all reported drinking alcohol.

Eight cannabis users reported smoking cannabis in the last three months. Two respondents reported smoking cannabis infrequently (less often than once a month), one reported smoking one to two times a week, and three reported daily use.

No respondents reported only breathing vaporized cannabis, although one participant reported using vaporized cannabis in addition to smoking and using medicinal cannabis. Two participants reported eating cannabis, one in addition to smoking it. Three respondents used medicinal cannabinoids (i.e., Dronabinol). Of the three respondents who used medicinal cannabinoids, one reported using only medicinal cannabinoids, one also smoked cannabis, and one both smoked as well as breathed vaporized cannabis.

Symptoms

The intensity of ALS-related symptoms was quantified by asking respondents to rate how much they experience each of the symptoms on a five-point scale ranging from "not at all" (0) to "very much" (4). The most frequent sympotm was weakness, followed by speech difficulties, drooling and swalowing difficulties. The intnesity of symptoms reported by respondents who did not use cannabis was not statistically significantly idfferent from the symptom intensity reported by the cannabis users [F(10, 120)=120) 1.07,=1.07, p=.39]. A summary of symptoms and their intensity is listed in Table 3.

The ammount of relief attributed to cannabis use was assessed by asking the respondents to rate the degree to which cannabis alleviates each symptom on a five-point scale ranging from "not at all" (0) to "completely relieves the symptom" (4). Respondents reported that the use of cannabis helped moderately for depression, appetite loss, spasticity, drooling, and pain. All cannabis users who reported symptoms of appetite loss and depression also reported that cannabis reduced these symptoms. None of the cannabis users reported any reduction in difficulties with swallowing and speech or sexual dysfunction.

The duration of symptom relief was measured on a scale from 0 (no relief) to 6 (more than nine hours). Respondents reported the most lasting relief (on average two to three hours) for depression. The loss of appetite, drooling, shortness of breath, spasticity, and pain were reported to be relieved on average for approximately one hour or less. Table 4 provides a summary of symptoms reported by the cannabis users. Level of relief was reported on a five-point scale ranging from "not at all" (0) to "completely relieves the symptom" (4). The duration of sumptom relief was measured on a scale from "no relief" (0), "less than one hour" (1), "two to three hours" (2), "four to five hours" (3), "six to seven hours" (4), "eight to nine hours" (5), "more than nine hours" (6).

Discussion

There is an increasing amount of research concerning the medicinal effects of cannabinoids. For example, cannabinoids have been reported to reduce chemotherapy-induced nausea and vomiting, lower intraocular pressure in patients with glaucoma, reduce anorexia in patients with cancer and AIDS-associated weight loss, and reduce pain and spasticity in MS.30-39 Cannabinoids, the active ingredients in marijuana, may also have properties that may be applicable to the management of ALS.9,10 However, to date no empirical studies of use and effectiveness of cannabis for symptom management by PALS have been published.

Approximately 10 percent of the survey respondents reported using cannabis. This is a lower rate than the frequency of use reported by other patient populations, including MS, AIDS, and cancer patients.10,30,31 However, the pattern of symptom relief reported by the small number of PALS who reported using cannabis for symptom management by people with other conditions, including MS.30,35,36 Cannabis users reported that cannabis smoking was most effective at reducing depression, appetite loss, pain, spasticity, drooling, and weakness. The factor that most predicted current use of cannabis by PALS was reported previous use (presumably recreational).

The survey had a number of limitations. First, the survey results reported here are based on a relatively small number of respondents (131) and on reports of 13 cannabis users, and may not be representative of the patterns of cannabis use in the ALS population by people with ALS in general. Second, 75 percent of the respondents were male, 25 percent were female. Men appear to be about 1.5 times more likely to be affected with ALS than women,7,8 so the percentage of female participants is slightly lower than expected in the general ALS population (about 33 percent). Published studies of Internet use consistently report that females are less likely to use the Internet for reasons that may be independent of income and estimate that only about one-third of Internet users are women.47,48 This may account for the lower than expected participation by women with ALS.

A third limitation of the study is that a disproportionate number of the survey respondents were white (90 percent) and all cannabis users were white. There is some evidence that whites may be at higher risk for ALS though most researchers agree that ALS equally affects people of all races.49,50 Racial discrepancies in rates of ALS may be due to poorer access to healthcare for minority populations in the US, particularly access to tertiary referral centers, where the ALS diagnosis is often made. Published studies report that over 80 percent of Internet users are white;48 this is the most likely explanation for the disproportionate perticipation by Caucasians in this survey.

Fourth, Internet users tend to be highly educated. Almost 60 percent repoert having at least one degree.48 Those with higher education are more likely to own computer equipment and to use it to connect to the Internet.51 The results of the survey we report here provide further evidence for this trend, with only 13 respondents (10 percent) reported having high school education or less.

Finally, none of the participants from the countries where cannabis use is prevalent (India) or legal for medical uses (Australia, Canada) reported using cannabis. The most likely explanation for this finding is the small number of perticipants from these countries; only one respondent was from India, six from Australia, and eleven from Canada.

In general, professionals with university degrees living in households with disposable incomes sufficient to purchase technology tools are likely to be over-represented in Internet surveys. Women, minorities, the elderly, those who liveon social assistance disability payments, or who earn minimum wages, are much less likely to participate.48,51

Privacy is a major issue associated with Web-based methodology. When the Internet is used for research, especially for research on sensitive issues (such as using substances that are illegal under federal law and most state laws), protecting the privacy of the participants is paramount. By making the survey anonymous, the authors protected the privacy of the respondents but gave up the ability to verify respondent' diagnoses or prevent repeated or malicious submittals. Although the records showed that no two responses were submitted from the same IP address, the IP address identifies the computer, not the user. Therefore, it cannot be conclusively determined that one respondent did not submit more than one response using different computers.

The low response rate might be explained by many factors. First, we do not know how many participants in the electronic discussion list that was used to recruit participants have ALS. It is possible, even likely, that a large majority of the participants are family members, service providers, and advocates. Second, the respondents who do not use alternative therapies may have been less likely to respond. It is unclear what percentage of people with ALS use alternative therapies. A recent survey from Germany suggests that about half of the ALS patients there use complementary and alternative medicine.52 Some respondents who do not use alternative therapies such as vitamins and supplements, but do use cannabis to manage their symptoms may not have considered cannabis to be an "alternative therapy" and decided not to participate. Many respondents provided information on vitamins, supplements, and other alternative therapies in the write-in spaces of the survey even though they were nto asked about these therapies directly, probably because the respondents had anticipated the survey would gather informationon those topics. Third, even though the invitation as well as the introduction to the survey clearly stated that the survey was anonymous and there was no way for the researchers to associate a specific response with a specific respondent, many may have been individuals who are generally suspicious of providing information via the Internet and may have decided not to participate for this reason.

Despite the limitations of this study noted above, these preliminary findings support the need for further research into the potential benefits of cannabis use for the clinical management of some ALS symptoms. These include pain, which was one of the symptoms identified in a recent study as not being sufficiently addressed in ALS.53 Further research is needed to see if the current findings can be confirmed using non-Internet-based survey methodology with a defined sample. It would also be informative to inquire about cannabis use within the context of subject beliefs about the efficacy of various alternative and complimentary approaches and their engagement and satisfaction with those approaches.

Acknowledgements

Funding for this research was provided by grants from the National Institute on Disability and Rehabilitation Research, Washington, DC and from the National Institutes of Health

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34. Nelson K, Walsh D, Deeter P, et al.: A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care. 1994; 10(1): 14-18.

35. Meinck HM, Schonle PW, Conrad B: Effects of cannabinoids on spasticity and ataxia in multiple sclerosis. J Neurol. 1989; 263(2): 120-122.

36. Greenberg HS, Weiness AS, Pugh JE: Short term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther. 1994; 55: 324-328.

37. Renn E, Mandel S, Mandel E: The medicinal uses of marijuana. Pharm Ther. 2000; 25(10): 536-524.

38. Gurley RJ, Aranow R, Katz M: Medicinal marijuana: A comprehensive review. J Psychoactive Drugs. 1998; 30(2): 137-147.

39 Voth EA, Schwartz RH: Medicinal applications of delta-9-tetrahydrocannabinol and marijuana. Ann Intern Med. 1997; 126(10): 791-798.

40. Meng Id, Manning BH, Martin WJ, et al.: An analgesia circuit activated by cannabinoids. Nature. 1998; 395(6700): 381-383.

41. Noyes R, Brunk SF, Baram DA, et al.: Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol. 1975a; 15(2-3): 139-143.

42. Zeltser R, Seltzer Z, Eisen A, et al.: Suppression of neuropathic pain behavior in rats by a non-psychotropic synthetic cannabinoid with NMDA receptor-blocking properties. Pain. 1991; 47(1): 95-103.

43. Noyes R, Brunk SF, Avery DAH, et al.: The analgesic properties of delta-9-tetrahydracannabinol. Clin Pharmacol Ther. 1975b; 18(1):84-89.

44. Richardson JD. Cannabinoids modulate pain by multiple mechanisms of action. J Pain. 2000; 1(1): 1-20.

45. Carter GT, Butler LM, Abresch RT, et al.: Expanding the role of hospice in the care of amyotrophic lateral sclerosis. Am J Hosp Palliat Care. 1999; 16(6): 707-710.

46. National Institute on Drug Abuse. Reserach Report Series: Marijuana Abuse. Bethesda, MD: National Institutes on Health, 2003.

47. Edsworth SM: World Wide Web: Opportunities, challenges, and threats. Lupus. 1999; 8: 596-605.

48. Kehoe C, Pitkow J, Sutton K, et al.: Results of GVU's Tenth World Wide Web User Survey. Georgia Institute of Technology, Graphics Visualization and Usability Center, College of Computing, Atlanta, Georgia. Available at WWW.gvu.gatech.edu/user_surveys/survey-1998-10/tenthreport.html. Accessed May 14, 1999.

49. Leone M, Chandra V, Schoenberg BS: Motor neuron disease in the United States, 1971 and 1973-1978: Patterns of mortality and associated conditions at the time of death. Neurology. 1987; 37(8): 1339-1343.

50. Lilenfeld DE, Chan E, Ehland J, et al.: Rising mortality from motoneuron disease in the USA, 1962-84. Lancet. 1989; 1(8640): 710-713.

51. Kaye S: Computer and Internet Use Among People with Disabilities. Washington, DC: NIDRR, US Dept. of Education, 2000.

52. Wasner M, Klier H, Borasio GD: The use of alternative medicine by patients with amyotrophic lateral sclerosis. J Neurol Sci. 2001; 191(1-2): 151-154.

53. Mandler RN, Anderson FA, Miller RG, et al.: ALS C.A.R.E. Study Group. The ALS patient care database: insights in to end-of-life care in ALS. Amyotroph Lateral Scler Other Motor Neruon Disord. 2001; 2(4): 203-208

source: http://www.cannabism...rts/carter4.php

Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid.
Raman C, McAllister SD, Rizvi G, Patel SG, Moore DH, Abood ME.

Forbes Norris MDA/ALS Research Center, 2351 Clay Street, Suite 416, California Pacific Medical Center, San Francisco, CA 94115, USA.

Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.

source: http://www.ncbi.nlm....Pubmed_RVDocSum


Reply
#2
Amyotrophic Lateral Sclerosis (ALS)



http://www.youtube.com/watch?v=d6nX8ecP5II




Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrigs Disease, is a fatal neurodegenerative disorder that is characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. An estimated 30,000 Americans are living with ALS, which often arises spontaneously and afflicts otherwise healthy adults. More than half of ALS patients die within 2.5 years following the onset of symptoms.

A review of the scientific literature reveals an absence of clinical trials investigating the use of cannabinoids for ALS treatment. However, recent preclinical findings indicate that cannabinoids can delay ALS progression, lending support to anecdotal reports by patients that cannabinoids may be efficacious in moderating the diseases development and in alleviating certain ALS-related symptoms such as pain, appetite loss, depression and drooling.[1]

Writing in the March 2004 issue of the journal Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, investigators at the California Pacific Medical Center in San Francisco reported that the administration of THC both before and after the onset of ALS symptoms staved disease progression and prolonged survival in animals compared to untreated controls.[2]

Additional trials in animal models of ALS have shown that the administration of other naturally occurring and synthetic cannabinoids can also moderate ALS progression, but not necessarily impact survival.[3-4] One recent study demonstrated that blocking the CB1 cannabinoid receptor did extend life span in an ALS mouse model, suggesting that cannabinoids beneficial effects on ALS may be mediated by non-CB1 receptor mechanisms.[5]

Preclinical data has also shown that cannabinoids are neuroprotective against oxidative damage both in vitro[6] and in animals.[7] Cannabinoids neuroprotective action may be able to play a role in moderating ALS, which is characterized by excessive glutamate activity in the spinal cord.[8] At least one cannabinoid, delta-9-THC, has been shown to protect cultured mouse spinal neurons against excitotoxicity.[9]

As a result, some experts now recommend that marijuana be considered in the pharmacological management of ALS,[10] and they believe that further investigation into the usefulness of marijuana and synthetic cannabinoid receptor agonists is warranted.[11]

REFERENCES

[1] Amtmann et al. 2004. Survey of cannabis use in patients with amyotrophic lateral sclerosis. The American Journal of Hospice and Palliative Care 21: 95-104.

[2] Raman et al. 2004. Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 5: 33-39.

[3] Weydt et al. 2005. Cannabinol delays symptom onset in SOD1 transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 6: 182-184.

[4] Bilsland et al. 2006. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. The FASEB Journal 20: 1003-1005.

[5] Ibid.

[6] Raman et al. 2004. op.cit.

[7] Hampson et al. 1998. Cannabidiol and delta-9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences 95: 8268-8273.

[8] Carter and Weydt. 2002. Cannabis: Old medicine with new promise for neurological disorders. Current Opinion in Investigational Drugs 3: 437-440.

[9] Abood et al. 2001. Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity. Neuroscience Letters 309: 197-201.

[10] Carter and Rosen. 2001. Marijuana in the management of amyotrophic lateral sclerosis. The American Journal of Hospice and Palliative Care 18: 264-70.

[11] Carter et al. 2003. Drug therapy for amyotrophic lateral sclerosis: Where are we now? The Investigational Drugs Journal 6: 147-153.


source: [/url][url=?Group_ID=7004%5B/url%5D]http://www.norml.org...m?Group_ID=7004


Why choose Mayo Clinic
At Mayo Clinic, doctors who have training in neuromuscular conditions (neurologists) and several other specialists work closely as a team to care for people who have this condition. Doctors offer treatment and continuing care that can address your medical needs and improve your quality of life. Mayo Clinic offers you and your family many resources for support, information and education.

Mayo Clinic in Rochester, Minn., is ranked among the Best Hospitals for neurology and neurosurgery by U.S. News & World Report.

Read more about Lou Gehrig's disease at MayoClinic.com.
Reply
#3
Marijuana May Extend Life Expectancy Of Lou Gehrig's Disease Patients, Study Says



Friday, 21 May 2010



Seattle, WA(ENEWSPF)May 21, 2010. Cannabis therapy may reduce symptoms and prolong survival in patients diagnosed with amyotrophic lateral sclerosis (ALS aka Lou Gehrig's disease), according to a scientific review published online last week by the American Journal of Hospice & Palliative Medicine.



Investigators at the University of Washington Medical Center in Seattle and Temple University in Pennsylvania reviewed preclinical and anecdotal data indicating that marijuana appears to treat symptoms of ALS as well as moderate the course of the disease.



Authors wrote: "Preclinical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. ... Cannabis also has properties applicable to symptom management of ALS, including analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. ... From a pharmacological perspective, cannabis is remarkably safe with realistically no possibility of overdose or frank physical addiction. There is a valid, logical, scientifically grounded rationale to support the use of cannabis in the pharmacological management of ALS."



They added, "Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease."



Investigators concluded, "There is an overwhelming amount of preclinical and clinical evidence to warrant initiating a multicenter randomized, double-blind, placebo-controlled trial of cannabis as a disease-modifying compound in ALS."



Writing in the March 2004 issue of the journal Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, investigators at the California Pacific Medical Center in San Francisco reported that the administration of THC both before and after the onset of ALS symptoms staved disease progression and prolonged survival in animals compared to untreated controls. To date, however, no clinical trials have assessed the use of marijuana or any of the plant's cannabinoids on patients diagnosed with ALS.



Lou Gehrig's Disease is a fatal, progressive neurodegenerative disorder that is characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. An estimated 30,000 Americans are living with ALS, which often arises spontaneously and afflicts otherwise healthy adults. An estimated 70 to 80 percent of patients with ALS die within three to five years following the onset of disease symptoms.



source: http://www.enewspf.c...nts-study-says-
Reply
#4
Am J Hosp Palliat Care. 2010 Aug;27(5):347-56. Epub 2010 May 3.

Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials.



Carter GT, Abood ME, Aggarwal SK, Weiss MD.



Muscular Dystrophy Association/Amyotrophic Lateral Sclerosis Center, University of Washington Medical Center, Seattle, WA, USA. gtcarter@uw.edu

Abstract



Significant advances have increased our understanding of the molecular mechanisms of amyotrophic lateral sclerosis (ALS), yet this has not translated into any greatly effective therapies. It appears that a number of abnormal physiological processes occur simultaneously in this devastating disease. Ideally, a multidrug regimen, including glutamate antagonists, antioxidants, a centrally acting anti-inflammatory agent, microglial cell modulators (including tumor necrosis factor alpha [TNF-alpha] inhibitors), an antiapoptotic agent, 1 or more neurotrophic growth factors, and a mitochondrial function-enhancing agent would be required to comprehensively address the known pathophysiology of ALS. Remarkably, cannabis appears to have activity in all of those areas. Preclinical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. In the G93A-SOD1 ALS mouse, this has translated to prolonged neuronal cell survival, delayed onset, and slower progression of the disease. Cannabis also has properties applicable to symptom management of ALS, including analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. With respect to the treatment of ALS, from both a disease modifying and symptom management viewpoint, clinical trials with cannabis are the next logical step. Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.



source: http://www.ncbi.nlm....pubmed/20439484
Reply
#5
Amyotrophic lateral sclerosis



From Wikipedia, the free encyclopedia

Jump to: navigation, search

"ALS" redirects here. For other uses, see ALS (disambiguation). Amyotrophic lateral sclerosis

(Lou Gehrig's or motor neurone disease) Classification and external resources [Image: 230px-ALS_Coronal.jpg]

This MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS. ICD-10 G12.2 ICD-9 335.20 OMIM 105400 DiseasesDB 29148 MedlinePlus 000688 eMedicine neuro/14 emerg/24 pmr/10 MeSH D000690

Amyotrophic lateral sclerosis (ALS) also referred to as motor neurone disease in some British Commonwealth countries and as Lou Gehrig's disease in North America is a debilitating disease with varied etiology characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and difficulty breathing (dyspnea). ALS is the most common of the five motor neuron diseases.



Contents


[*]2 Cause



[*]3 Pathophysiology


[*]4 Diagnosis



[*]5 Treatment






</li>
</ul>
[*]6 Epidemiology



[*]7 Etymology



[*]8 History



[*]9 Clinical research



[*]10 See also



[*]11 References



[*]12 Further reading



[*]13 External links



</li></ul>


Signs and symptoms



The disorder causes muscle weakness and atrophy throughout the body caused by degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and atrophy. Affected individuals may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared.<sup>[1]</sup>

Cognitive function is generally spared for most patients, although some (about 5%) also have frontotemporal dementia.<sup>[2]</sup> A higher proportion of patients (3050%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS will maintain sight, hearing, touch, smell, and taste.

Initial symptoms



The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include muscle fasciculation (twitching), cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. 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 contracting the disease experience "limb onset" ALS, i.e., first symptoms in the arms or legs. Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a "dropped foot" which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.

About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. Other symptoms include difficulty swallowing and loss of tongue mobility. A smaller proportion of patients experience "respiratory onset" ALS, where the intercostal muscles that support breathing are affected first. A small proportion of patients may also present with what appears to be frontotemporal dementia, but later progresses to include more typical ALS symptoms.

Over time, 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 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 1545% of patients experience pseudobulbar affect, also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor exp<b></b>ressions of emotion. 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.

Disease progression and spread



Although the order and rate of symptoms varies from person to person, eventually most patients are not able to walk, get out of bed on their own, or use their hands and arms. The rate of progression can be measured using an outcome measure called the "ALS Functional Rating Scale (Revised)", a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). Though there is a high degree of variability and a small percentage of patients have much slower disease, on average, patients lose about 1 FRS point per month. 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. In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in bulbar-onset ALS symptoms typically spread to the arms before the legs.

Disease progression tends to be slower in patients who are younger than 40 at onset,<sup>[3]</sup> have disease restricted primarily to one limb, and those with primarily upper motor neuron symptoms.<sup>[4]</sup> Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disease, respiratory-onset disease, and frontotemporal dementia.<sup>[4]</sup>

Late stage disease symptoms



Difficulty swallowing and chewing making eating normally very difficult and increase the risk of choking or aspirating food into the lungs. In later stages of the disease, aspiration pneumonia and maintaining a healthy weight can become a significant problem and may require insertion of a feeding tube. As the diaphragm and intercostal muscles (rib cage) that support breathing weaken, measures of lung function such as forced vital capacity and inspiratory pressure diminish. In respiratory onset ALS, this may occur before significant limb weakness is apparent. External machines such as bilevel positive pressure ventilation (frequently referred to by the tradename BiPAP) are frequently used to support breathing, first at night, and later during the daytime as well. BiPAP is only a temporary remedy, however, and it is recommended that long before BiPAP stops being effective, patients should decide whether to have a tracheotomy and long term mechanical ventilation. At this point, some patients choose palliative hospice care. Most people with ALS die of respiratory failure or pneumonia.

Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years.<sup>[5]</sup> The best-known person with ALS, Stephen Hawking, has lived with the disease for more than 50 years, though his is an unusual case.<sup>[6]</sup>

Cause



Where no family history of the disease is present i.e., in around 95% of cases there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in contact sports. Many other potential causes, including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock, have been investigated but without consistent findings.<sup>[7]</sup>

There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families. Recently, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9ORF72, which is associated with ALS combined with frontotemporal dementia ALS-FTD,<sup>[8]</sup> and accounts for some 6% of cases of ALS among white Europeans.<sup>[9]</sup> The high degree of mutations found in patients that appeared to have "sporadic" disease, i.e. without a family history, suggests that genetics may play a more significant role than previously thought and that environmental exposures may be less relevant.

A defect on chromosome 21 (coding for superoxide dismutase) is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall.<sup>[10]</sup><sup>[11]</sup><sup>[12]</sup> This mutation is believed to be autosomal dominant, and has over a hundred different forms of mutation. The most common ALS-causing SOD1 mutation in North American patients is A4V, characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A, is more slowly progressive than typical ALS and patients with this form of the disease survive for an average of 11 years.<sup>[13]</sup>

Mutations in several genes have also been linked to various types of ALS, and the currently identified associations are shown in the table below: Genetic associations include Type OMIM Gene Locus ALS1 105400 SOD1 21q22.1 ALS2 205100 ALS2 2q33.1 ALS3 606640 ? 18q21 ALS4 602433 SETX 9q34.13 ALS5 602099 ? 15q15.1-q21.1 ALS6 608030 FUS 16p11.2 ALS7 608031 ? 20p13 ALS8 608627 VAPB 20q13.3 ALS9 611895 ANG 14q11.2 ALS10 612069 TARDBP 1p36.2 ALS11 612577 FIG4 6q21 ALS12 613435 OPTN 10p15-p14 ALS13 183090 ATXN2 12q24.12 ALS14 613954 VCP 9p13.3

Pathophysiology



The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.<sup>[14]</sup> These inclusions often contain ubiquitin, and generally incorporate one of the ALS-associated proteins: SOD1, TAR DNA binding protein (TDP-43, or TARDBP), or FUS.

SOD1



[Image: 50px-Merge-arrow.svg.png] It has been suggested that this article or section be merged into SOD1. (Discuss) Proposed since June 2012.

The cause of ALS is not known, though an important step toward determining the cause came in 1993 when scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase (SOD1) enzyme were associated with some cases (approximately 20%) of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive molecules produced by cells during normal metabolism again largely by the mitochondria. Free radicals can accumulate and cause damage to both mitochondrial and nuclear DNA and proteins within cells. To date, over 110 different mutations in SOD1 have been linked with the disease, some of which have a very long clinical course (e.g. H46R), while others, such as A4V, being exceptionally aggressive. Evidence suggests that failure of defenses against oxidative stress up-regulates programmed cell death (apoptosis), among many other possible consequences. 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. Current research, however, indicates that motor neuron death is not likely a result of lost or compromised dismutase activity, suggesting mutant SOD1 induces toxicity in some other way (a gain of function).<sup>[15]</sup><sup>[16]</sup>

Studies involving transgenic mice have yielded several theories about the role of SOD1 in mutant SOD1 familial amyotrophic lateral sclerosis. Mice lacking the SOD1 gene entirely do not customarily develop ALS, although they do exhibit an acceleration of age-related muscle atrophy (sarcopenia) and a shortened lifespan (see article on superoxide dismutase). This indicates that the toxic properties of the mutant SOD1 are a result of a gain in function rather than a loss of normal function. In addition, aggregation of proteins has been found to be a common pathological feature of both familial and sporadic ALS (see article on proteopathy). Interestingly, in mutant SOD1 mice (most commonly, the G93A mutant), aggregates (misfolded protein accumulations) of mutant SOD1 were found only in diseased tissues, and greater amounts were detected during motor neuron degeneration.<sup>[17]</sup> It is speculated that aggregate accumulation of mutant SOD1 plays a role in disrupting cellular functions by damaging mitochondria, proteasomes, protein folding chaperones, or other proteins.<sup>[18]</sup> Any such disruption, if proven, would lend significant credibility to the theory that aggregates are involved in mutant SOD1 toxicity. Critics have noted that in humans, SOD1 mutations cause only 2% or so of overall cases and the etiological mechanisms may be distinct from those responsible for the sporadic form of the disease. To date, the ALS-SOD1 mice remain the best model of the disease for preclinical studies but it is hoped that more useful models will be developed.

Other factors



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.<sup>[11]</sup> Riluzole is currently the only FDA approved drug for ALS and targets glutamate transporters. It only has a modest effect on survival, however, suggesting that excess glutamate is not the sole cause of the disease.

Diagnosis



No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.



[Image: 220px-ALS_cross.jpg]



[Image: magnify-clip.png]MRI (axial FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule, consistent with the clinical diagnosis of ALS.

Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis.

Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.

Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease,<sup>[19]</sup> syphilis<sup>[20]</sup> and tick-borne encephalitis<sup>[21]</sup> viruses can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, and spinal muscular atrophy can also mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis.

ALS must be differentiated from the ALS mimic syndromes which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants.<sup>[22]</sup> Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients should always obtain a second neurological opinion.

However, most cases of ALS are readily diagnosed and the error rate of diagnosis in large ALS clinics is less than 10%.<sup>[23]</sup><sup>[24]</sup> In one study, 190 patients who met the MND / ALS diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. Thirty of these patients (15.78%) had their diagnosis completely changed, during the clinical observation development period.<sup>[25]</sup> In the same study, three patients had a false negative diagnoses, myasthenia gravis (MG), an auto-immune disease. MG can mimic ALS and other neurological disorders leading to a delay in diagnosis and treatment. MG is eminently treatable; ALS is not.<sup>[26]</sup> Myasthenic syndrome, also known as Lambert-Eaton syndrome (LES),can mimic ALS and its initial presentation can be similar to that of MG.<sup>[27]</sup><sup>[28]</sup>

Treatment



Slowing progression



Riluzole (Rilutek) is the only treatment that has been found to improve survival but only to a modest extent.<sup>[29]</sup> It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage (occurring in ~10% of people taking the drug).<sup>[30]</sup> It is approved by Food and Drug Administration (FDA) and recommended by the National Institute for Clinical Excellence (NICE).

Disease management



Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible.

Pharmaceutical treatments



Medical professionals can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, dysphagia, and constipation. Baclofen and diazepam are often prescribed to control the spasticity caused by ALS, and trihexyphenidyl or amitriptyline may be prescribed when ALS patients begin having trouble swallowing their saliva.<sup>[1]</sup>

Physical, occupational and speech therapy



Physical therapists and occupational therapists play a large role in rehabilitation for individuals with ALS. Specifically, physical and occupational therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, preventing complications, and promoting functional independence.<sup>[31]</sup>

Occupational therapy and special equipment such as assistive technology can also enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living (ADL's), walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.) and wheelchairs that help patients remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable people to retain as much safety and independence in activities of daily living as possible.

ALS patients who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) and/or low tech communication techniques such as alphabet boards or yes/no signals.

Feeding and nutrition



Patients and caregivers can learn from speech-language pathologists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. Occupational therapists can assist with recommendations for adaptive equipment to ease the physical task of self-feeding and/or make food choice recommendations that are more conducive to their unique deficits and abilities. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.

Researchers have stated that "ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake."<sup>[32]</sup> Both animal<sup>[33]</sup> and human research<sup>[32]</sup><sup>[34]</sup> suggest that ALS patients should be encouraged to consume as many calories as possible and not to restrict their calorie intake.

Breathing support



When the muscles that assist in breathing weaken, use of ventilatory assistance (intermittent positive pressure ventilation (IPPV), bilevel positive airway pressure (BIPAP), or biphasic cuirass ventilation (BCV)) may be used to aid breathing. Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time. BCV has the added advantage of being able to assist in clearing secretions by using high-frequency oscillations followed by several positive expiratory breaths.<sup>[35]</sup> Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheostomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck.

Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support. Some patients under long-term tracheostomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheostomy tubes (leak ventilation) are able to speak, provided their bulbar muscles are strong enough. This technique preserves speech in some patients with long-term mechanical ventilation.

Palliative care



Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Home nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving feedings, and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.

Epidemiology



ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. One or two out of 100,000 people develop ALS each year.<sup>[36]</sup> 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.

Although the incidence of ALS is thought to be regionally uniform, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS. 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.<sup>[37]</sup> Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan.<sup>[38]</sup><sup>[39]</sup>

Although there have been reports of several "clusters" including three American football players from the San Francisco 49ers, more than fifty football players in Italy,<sup>[40]</sup> three football-playing friends in the south of England,<sup>[41]</sup> and reports of conjugal (husband and wife) cases in the south of France,<sup>[42]</sup><sup>[43]</sup><sup>[44]</sup><sup>[45]</sup><sup>[46]</sup> these are statistically plausible chance events<sup>[</sup><sup>citation needed</sup><sup>]</sup>. 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.

Etymology



Amyotrophic comes from the Greek language: A- means "no", myo refers to "muscle", and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic atrophication of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region.

History

Timeline Year Event 1824 Charles Bell writes a report about ALS.<sup>[47]</sup> 1850 English scientist Augustus Waller describes the appearance of shriveled nerve fibers 1869 French doctor Jean-Martin Charcot first describes ALS in scientific literature<sup>[48]</sup> 1881 "Amyotrophic Lateral Sclerosis" is translated into English and published in a three-volume edition of Lectures on the Diseases of the Nervous System 1939 ALS becomes a cause clbre in the United States when baseball legend Lou Gehrig's careerand, two years later, his lifeis ended by the disease. He gives his farewell speech on 4 July 1939.<sup>[49]</sup> 1950s ALS epidemic occurs among the Chamorro people on Guam 1991 Researchers link chromosome 21 to FALS (Familial ALS) 1993 SOD1 gene on chromosome 21 found to play a role in some cases of FALS 1996 Rilutek becomes the first FDA-approved drug for ALS 1998 The El Escorial criteria is developed as the standard for classifying ALS patient in clinical research 1999 The revised ALS Functional Rating Scale (ALSFRS-R) is published and soon becomes a gold standard measure for rating decline in ALS patient in clinical research 2011 Noncoding repeat expansions in C9ORF72 are found to be a major cause of ALS and frontotemporal dementia

Clinical research



A number of clinical trials are underway globally for ALS; a comprehensive listing of trials in the US can be found at ClinicalTrials.gov.

Thalidomide and Lenalidomide have shown efficacy in protecting motor neurons in transgenic (G93A) mice <sup>[50]</sup>http://www.jneurosci...7.full.pdf html.

KNS-760704 (Dexpramipexole) is under clinical investigation in ALS patients. It is hoped that the drug will have a neuroprotective effect. It is one enantiomer of pramipexole, which is approved for the treatment of Parkinson's disease and restless legs syndrome.<sup>[51]</sup> The single-enantiomer preparation is essentially inactive at dopamine receptors, is not dose limited by the potent dopaminergic properties of pramipexole.<sup>[52]</sup> Results of a Phase II clinical trial conducted by Knopp Neurosciences and involving 102 patients were reported in 2010; the trial found a dose-dependent slowing in loss of function.<sup>[53]</sup> A larger phase II trial conducted by Biogen found the drug to be safe, well tolerated, and associated with a dose-dependent slowing in the decline of ALS.<sup>[54]</sup>

Talampanel is being tested in ALS by Teva Pharmaceutical Industries; a Phase II trial was completed in April 2010.<sup>[55]</sup>

See also




References





<ol style="list-style-type: decimal">
[*]^ <sup>a</sup> <sup>b</sup> http://www.ncbi.nlm....lth/PMH0001708/



[*]
^ Phukan J, Pender NP, Hardiman O (2007). "Cognitive impairment in amyotrophic lateral sclerosis". Lancet Neurol 6 (11): 9941003. doi:10.1016/S1474-4422(07)70265-X. PMID 17945153.



[*]
^ M. Sabatelli, MD, F. Madia, MD, A. Conte, MD, M. Luigetti, MD, M. Zollino, MD, I. Mancuso, PhD, M. Lo Monaco, MD, G. Lippi, MD and P. Tonali, MD (2008). "Natural history of young-adult amyotrophic lateral sclerosis". Neurology 16 (71): 876881.



[*]^ <sup>a</sup> <sup>b</sup> Chio, A.; Calvo, A.; Moglia, C.; Mazzini, L.; Mora, G. (2011). "Phenotypic heterogeneity of amyotrophic lateral sclerosis: A population based study". Journal of Neurology, Neurosurgery & Psychiatry 82 (7): 740. doi:10.1136/jnnp.2010.235952. PMID 21402743. edit



[*]
^ M R Turner, M J Parton, C E Shaw, P N Leigh, A Al-Chalabi (2003). "Prolonged survival in motor neuron disease: a descriptive study of the Kings database 19902002.". J Neurol Neurosurg Psychiatry 74: 995997.



[*]
^ Stephen Hawking serves as role model for ALS patients



[*]
^ Sutedja NA, Fischer K, Veldink JH, van der Heijden GJ, Kromhout H, Heederik D, et al. (2009). "What we truly know about occupation as a risk factor for ALS: a critical and systematic review.". Amyotrophic Lateral Sclerosis 10: 295301.



[*]
^ Dejesus-Hernandez, M., et al., (2011). "Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS.". Neuron 72 (2): 24556.



[*]
^ Majounie E., et al., (2012). "Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study.". Lancet Neurology 11 (4): 323330.



[*]
^ Conwit, Robin A. (December 2006). "Preventing familial ALS: A clinical trial may be feasible but is an efficacy trial warranted?". Journal of the Neurological Sciences 251 (12): 12. doi:10.1016/j.jns.2006.07.009. ISSN 0022-510X. PMID 17070848.



[*]^ <sup>a</sup> <sup>b</sup> Al-Chalabi, Ammar; P. Nigel Leigh (August 2000). "Recent advances in amyotrophic lateral sclerosis". Current Opinion in Neurology 13 (4): 397405. doi:10.1097/00019052-200008000-00006. ISSN 1473-6551. PMID 10970056.



[*]
^ Battistini S, Ricci C, Lotti EM, Benigni M, Gagliardi S, Zucco R, Bondavalli M, Marcello N, Ceroni M, Cereda C (June 2010). "Severe familial ALS with a novel exon 4 mutation (L106F) in the SOD1 gene". Journal of the Neurological Sciences 293 (1): 112115. doi:10.1016/j.jns.2010.03.009. PMID 20385392.



[*]
^ Anderson P.M., et al., (1996). "Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation, A clinical and genealogical study of 36 patients.". Brain 119: 11531172.



[*]
^ Deng, HX; Chen, W, Hong, ST, Boycott, KM, Gorrie, GH, Siddique, N, Yang, Y, Fecto, F, Shi, Y, Zhai, H, Jiang, H, Hirano, M, Rampersaud, E, Jansen, GH, Donkervoort, S, Bigio, EH, Brooks, BR, Ajroud, K, Sufit, RL, Haines, JL, Mugnaini, E, Pericak-Vance, MA, Siddique, T (2011-08-21). "Mutations in UBQLN2 cause dominant X-linked juvenile and adult onset ALS and ALS/dementia". Nature 477 (7363): 2115. doi:10.1038/nature10353. PMC 3169705. PMID 21857683.



[*]
^ Reaume A, Elliott J, Hoffman E, Kowall N, Ferrante R, Siwek D, Wilcox H, Flood D, Beal M, Brown R, Scott R, Snider W (1996). "Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury". Nat Genet 13 (1): 437. doi:10.1038/ng0596-43. PMID 8673102.



[*]
^ Bruijn L, Houseweart M, Kato S, Anderson K, Anderson S, Ohama E, Reaume A, Scott R, Cleveland D (1998). "Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1". Science 281 (5384): 18514. doi:10.1126/science.281.5384.1851. PMID 9743498.



[*]
^ Furukawa Y, Fu R, Deng H, Siddique T, O'Halloran T (2006). "Disulfide cross-linked protein represents a significant fraction of ALS-associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice". Proc Natl Acad Sci USA 103 (18): 714853. doi:10.1073/pnas.0602048103. PMC 1447524. PMID 16636274.



[*]
^ Boille S, Vande Velde C, Cleveland D (2006). "ALS: a disease of motor neurons and their nonneuronal neighbors". Neuron 52 (1): 3959. doi:10.1016/j.neuron.2006.09.018. PMID 17015226.



[*]
^ Hansel Y, Ackerl M, Stanek G. (1995). "ALS-like sequelae in chronic neuroborreliosis". Wien Med Wochenschr. 145 (78): 1868. PMID 7610670.



[*]
^ el Alaoui-Faris M, Medejel A, al Zemmouri K, Yahyaoui M, Chkili T (1990). "Amyotrophic lateral sclerosis syndrome of syphilitic origin. 5 cases". Rev Neurol (Paris) 146 (1): 414. PMID 2408129.



[*]
^ Umanekii KG, Dekonenko EP (1983). "Structure of progressive forms of tick-borne encephalitis". Zh Nevropatol Psikhiatr Im S S Korsakova. 83 (8): 11739. PMID 6414202.



[*]
^ Silani, V.; Messina, S.; Poletti, B.; Morelli, C.; Doretti, A.; Ticozzi, N.; Maderna, L. (2011). "The diagnosis of Amyotrophic lateral sclerosis in 2010". Archives italiennes de biologie 149 (1): 527. doi:10.4449/aib.v149i1.1260. PMID 21412713. edit



[*]
^ Eisen, A. (2002). "Amyotrophic lateral sclerosis: A review". BCMJ 44 (7): 362366.



[*]
^ Davenport, R. J.; Swingler, R. J.; Chancellor, A. M.; Warlow, C. P. (1996). "Avoiding false positive diagnoses of motor neuron disease: Lessons from the Scottish Motor Neuron Disease Register". ...
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Amyotrophic Lateral Sclerosis (ALS)<div><div><div>
[Image: pdf_file.gif] [Image: nerve.jpg][Image: 3dscience_credit.gif]Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal neurodegenerative disorder that is characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. An estimated 30,000 Americans are living with ALS, which often arises spontaneously and afflicts otherwise healthy adults. More than half of ALS patients die within 2.5 years following the onset of symptoms.

A review of the scientific literature reveals an absence of clinical trials investigating the use of cannabinoids for ALS treatment. However, recent preclinical findings indicate that cannabinoids can delay ALS progression, lending support to anecdotal reports by patients that cannabinoids may be efficacious in moderating the diseases development and in alleviating certain ALS-related symptoms such as pain, appetite loss, depression and drooling.[1]

Writing in the March 2004 issue of the journal Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders, investigators at the California Pacific Medical Center in San Francisco reported that the administration of THC both before and after the onset of ALS symptoms staved disease progression and prolonged survival in animals compared to untreated controls.[2]

Additional trials in animal models of ALS have shown that the administration of other naturally occurring and synthetic cannabinoids can also moderate ALS progression but not necessarily impact survival.[3-4] One recent study demonstrated that blocking the CB1 cannabinoid receptor did extend life span in an ALS mouse model, suggesting that cannabinoids' beneficial effects on ALS may be mediated by non-CB1 receptor mechanisms.[5]

As a result, experts are calling for clinical trials to assess cannabinoids for the treatment of ALS. Writing in the American Journal of Hospice & Palliative Medicine in 2010, a team of investigators reported, "Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease." They concluded, "There is an overwhelming amount of preclinical and clinical evidence to warrant initiating a multicenter randomized, double-blind, placebo-controlled trial of cannabis as a disease-modifying compound in ALS."[6]

REFERENCES

[1] Amtmann et al. 2004. Survey of cannabis use in patients with amyotrophic lateral sclerosis. The American Journal of Hospice and Palliative Care 21: 95-104.

[2] Raman et al. 2004. Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 5: 33-39.

[3] Weydt et al. 2005. Cannabinol delays symptom onset in SOD1 transgenic mice without affecting survival. Amyotrophic Lateral Sclerosis & Other Motor Neuron Disorders 6: 182-184.

[4] Bilsland et al. 2006. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. The FASEB Journal 20: 1003-1005.

[5] Ibid.

[6] Carter et al. 2010. Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. American Journal of Hospice & Palliative Medicine 27: 347-356.



Tests and diagnosis By Mayo Clinic staffAmyotrophic lateral sclerosis is difficult to diagnose early because it may appear similar to several other neurological diseases. Tests to rule out other conditions may include:
  • Electromyogram. This test measures the tiny electrical discharges produced in muscles. A fine wire electrode is inserted into the muscles that your doctor wants to study. An instrument records the electrical activity in your muscle as you rest and contract the muscle. Generally, this test is mildly uncomfortable.
  • Nerve conduction study. For this test, electrodes are attached to your skin above the nerve or muscle to be studied. A small shock, which may feel like a twinge or spasm, is passed through the nerve to measure the strength and speed of nerve signals.
  • MRI. Using radio waves and a powerful magnetic field, MRI can produce detailed images of your brain and spinal cord. It involves lying on a movable bed that slides into a tube-shaped machine that makes loud thumping and banging noises during operation. Some people feel uncomfortable in the confined space.
  • Blood and urine tests. Analyzing samples of your blood and urine in the laboratory may help your doctor eliminate other possible causes of your signs and symptoms.
  • Muscle biopsy. If your doctor believes you may have a muscle disease rather than ALS, you may undergo a muscle biopsy. In this procedure, a small portion of muscle is removed while you're under local anesthesia and is sent to a lab for analysis.
</div></div>
</div> How is ALS treated?



No cure has yet been found for ALS. However, the Food and Drug Administration (FDA) has approved the first drug treatment for the diseaseriluzole (Rilutek). Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole prolongs survival by several months, mainly in those with difficulty swallowing. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects. However, this first disease-specific therapy offers hope that the progression of ALS may one day be slowed by new medications or combinations of drugs.

Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals such as physicians; pharmacists; physical, occupational, and speech therapists; nutritionists; social workers; and home care and hospice nurses. Working with patients and caregivers, these teams can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.

Physicians can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, and constipation. Pharmacists can give advice on the proper use of medications and monitor a patient's prescriptions to avoid risks of drug interactions.

Physical therapy and special equipment can enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical therapists can recommend exercises that provide these benefits without overworking muscles. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve energy and remain mobile.

ALS patients who have difficulty speaking may benefit from working with a speech therapist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech therapists can help patients develop ways for responding to yes-or-no questions with their eyes or by other nonverbal means and can recommend aids such as speech synthesizers and computer-based communication systems. These methods and devices help patients communicate when they can no longer speak or produce vocal sounds.

Patients and caregivers can learn from speech therapists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.

When the muscles that assist in breathing weaken, use of nocturnal ventilatory assistance (intermittent positive pressure ventilation [iPPV] or bilevel positive airway pressure [bIPAP]) may be used to aid breathing during sleep. Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time.

Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheostomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck. Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support.

Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Respiratory therapists can help caregivers with tasks such as operating and maintaining respirators, and home care nurses are available not only to provide medical care but also to teach caregivers about giving tube feedings and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.

What research is being done?



The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is the Federal Government's leading supporter of biomedical research on ALS. The goals of this research are to find the cause or causes of ALS, understand the mechanisms involved in the progression of the disease, and develop effective treatment.

Scientists are seeking to understand the mechanisms that trigger selective motor neurons to degenerate in ALS and to find effective approaches to halt the processes leading to cell death. This work includes studies in animals to identify the means by which SOD1 mutations lead to the destruction of neurons. The excessive accumulation of free radicals, which has been implicated in a number of neurodegenerative diseases including ALS, is also being closely studied. In addition, researchers are examining how the loss of neurotrophic factors may be involved in ALS. Neurotrophic factors are chemicals found in the brain and spinal cord that play a vital role in the development, specification, maintenance, and protection of neurons. Studying how these factors may be lost and how such a loss may contribute to motor neuron degeneration may lead to a greater understanding of ALS and the development of neuroprotective strategies. By exploring these and other possible factors, researchers hope to find the cause or causes of motor neuron degeneration in ALS and develop therapies to slow the progression of the disease.

Researchers are also conducting investigations to increase their understanding of the role of programmed cell death or apoptosis in ALS. In normal physiological processes, apoptosis acts as a means to rid the body of cells that are no longer needed by prompting the cells to commit "cell suicide." The critical balance between necessary cell death and the maintenance of essential cells is thought to be controlled by trophic factors. In addition to ALS, apoptosis is pervasive in other chronic neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease and is thought to be a major cause of the secondary brain damage seen after stroke and trauma. Discovering what triggers apoptosis may eventually lead to therapeutic interventions for ALS and other neurological diseases.

Scientists have not yet identified a reliable biological marker for ALSa biochemical abnormality shared by all patients with the disease. Once such a biomarker is discovered and tests are developed to detect the marker in patients, allowing early detection and diagnosis of ALS, physicians will have a valuable tool to help them follow the effects of new therapies and monitor disease progression.

NINDS-supported researchers are studying families with ALS who lack the SOD1 mutation to locate additional genes that cause the disease. Identification of additional ALS genes will allow genetic testing useful for diagnostic confirmation of ALS and prenatal screening for the disease. This work with familial ALS could lead to a greater understanding of sporadic ALS as well. Because familial ALS is virtually indistinguishable from sporadic ALS clinically, some researchers believe that familial ALS genes may also be involved in the manifestations of the more common sporadic form of ALS. Scientists also hope to identify genetic risk factors that predispose people to sporadic ALS.

Potential therapies for ALS are being investigated in animal models. Some of this work involves experimental treatments with normal SOD1 and other antioxidants. In addition, neurotrophic factors are being studied for their potential to protect motor neurons from pathological degeneration. Investigators are optimistic that these and other basic research studies will eventually lead to treatments for ALS.

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