- adj.
- 筋萎縮性の
- ex.
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/06/21 15:18:12」(JST)
wiki en
"ALS" redirects here. For other uses, see ALS (disambiguation).
| Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease) |
|
|---|---|
| Classification and external resources | |
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 neuron disease in British English, is the most common form of the motor neuron diseases. The condition is sometimes called Lou Gehrig's disease in North America, after the New York Yankees baseball player who was diagnosed with the disease in 1939. The disorder is characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and decline in breathing ability.
Contents
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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.
Cognitive function is generally spared for most patients although some (~5%) also have frontotemporal dementia.[1] A higher proportion of patients (~30-50%) 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. Bladder and bowel functions are also rarely affected by ALS.[2]
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 15–45% 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 expressions 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[3], have disease restricted primarily to one limb, and those with primarily upper motor neuron symptoms.[4]. Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disease, respiratory-onset disease, and frontotemporal dementia. [5]
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. [6] The best-known person with ALS, Stephen Hawking, has lived with the disease for more than 50 years, though his is an unusual case.[7]
Cause
For patients without a family history of the disease, which includes ~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. [8]
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 [9], and accounts for some 6% of cases of ALS among white Europeans. [10] 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.[11][12][13] 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. [14]
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.[15] 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
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).[16][17]
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.[18] 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.[19] 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.[12] 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.
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,[20] syphilis[21] and tick-borne encephalitis[22] 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.
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.
Treatment
Slowing progression
Riluzole (Rilutek) as of 2011 is the only treatment that has been found to improve survival but only to a modest extent.[23] 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).[24] 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.[2]
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.[25]
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."[26] Both animal [27] and human research [26][28] 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.[29] 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.[30] 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.[31] Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan.[32][33]
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,[34] three football-playing friends in the south of England,[35] and reports of conjugal (husband and wife) cases in the south of France,[36][37][38][39][40] these are statistically plausible chance events[citation needed]. 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
| Year | Event |
|---|---|
| 1824 | Charles Bell writes a report about ALS.[41] |
| 1850 | English scientist Augustus Waller describes the appearance of shriveled nerve fibers |
| 1869 | French doctor Jean-Martin Charcot first describes ALS in scientific literature[42] |
| 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 célèbre in the United States when baseball legend Lou Gehrig's career—and, two years later, his life—is ended by the disease. He gives his farewell speech on July 4, 1939.[43] |
| 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.
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.[44] The single-enantiomer preparation is essentially inactive at dopamine receptors, is not dose limited by the potent dopaminergic properties of pramipexole.[45] 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.[46] 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.[47]
Talampanel is being tested in ALS by Teva Pharmaceutical Industries; a Phase II trial was completed in April 2010.[48]
See also
- ALS Association
- ALS Society of Canada
- ALS Therapy Development Institute
- Motor Neurone Disease Association
- Muscular Dystrophy Association
References
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- ^ Miller, RG; Mitchell JD, Lyon M, Moore DH, G (2007). Miller, Robert G. ed. "Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)". Cochrane Database of Systematic Reviews (1): CD001447. DOI:10.1002/14651858.CD001447.pub2. PMID 17253460.
- ^ Lewis, M. & Rushanan, S. (2007). "The role of physical therapy and occupational therapy in the treatment of Amyotrophic Lateral Sclerosis". NeuroRehabilitation 22 (6): 451–461. PMID 18198431.
- ^ a b Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ (Jan 1996). "Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death". Am J Clin Nutr. 63 (1): 130–7. PMID 8604660. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=8604660.
- ^ Hamadeh MJ, Rodriguez MC, Kaczor JJ, Tarnopolsky MA (Feb 2005). "Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse". Muscle Nerve 31 (2): 214–20. DOI:10.1002/mus.20255. PMID 15625688.
- ^ Slowie LA, Paige MS, Antel JP (Jul 1983). "Nutritional considerations in the management of patients with amyotrophic lateral sclerosis (ALS)". J Am Diet Assoc 83 (1): 44–7. PMID 6863783.
- ^ Sviri S, Linton DM, Van Heerden PV (Jun 2005). "Non-invasive Mechanical Ventilation Enhances Patient Autonomy in Decision-Making Regarding Chronic Ventilation". Critical Care and Resuscitation 7 (2): 116–118. PMID 16548804.
- ^ "ALS Topic Overview". Archived from the original on 1 May 2008. http://www.webmd.com/brain/tc/Amyotrophic-Lateral-Sclerosis-ALS-Topic-Overview. Retrieved 2008-05-01.
- ^ Reed D, Labarthe D, Chen KM, Stallones R (Jan 1987). "A cohort study of amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and Rota". Am J Epidemiol. 125 (1): 92–100. PMID 3788958. http://aje.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=3788958.
- ^ S. Kuzuhara, Y. Kokubo P3-146Marked increase of parkinsonism-dementia (P-D) phenotypes in the high incidence amyotrophic lateral sclerosis (ALS) focus in the Kii peninsula of Japan. Alzheimer's and Dementia, Volume 2, Issue 3, Pages S417-S417
- ^ Spencer PS, Palmer VS, Ludolph AC (Aug 2005). "On the decline and etiology of high-incidence motor system disease in West Papua (southwest New Guinea)". Mov. Disord. 20 (Suppl 12): S119–26. DOI:10.1002/mds.20552. PMID 16092101.
- ^ "Sla, indagini nei club. Pesticidi nel mirino". Archived from the original on 3 October 2008. http://www.corriere.it/sport/08_ottobre_03/sla_indagine_pesticidi_fd04f986-911c-11dd-9f28-00144f02aabc.shtml. Retrieved 2008-10-02.
- ^ Wicks P, Abrahams S, Masi D, Hejda-Forde S, Leigh PN & Goldstein LH (2005) The Prevalence of Depression and Anxiety in MND, Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders, Volume 6, Supplement 1, p. 147
- ^ Rachele MG, Mascia V, Tacconi P, Dessi N, Marrosu F (April 1998). "Conjugal amyotrophic lateral sclerosis: a report on a couple from Sardinia, Italy". Ital J Neurol Sci. 19 (2): 97–100. DOI:10.1007/BF02427565. PMID 10935845.
- ^ Poloni M, Micheli A, Facchetti D, Mai R, Ceriani F (April 1997). "Conjugal amyotrophic lateral sclerosis: toxic clustering or change?". Ital J Neurol Sci. 18 (2): 109–12. DOI:10.1007/BF01999572. PMID 9239532.
- ^ Camu W, Cadilhac J, Billiard M. (March 1994). "Conjugal amyotrophic lateral sclerosis: a report on two couples from southern France". Neurology 44 (3 Pt 1): 547–8. PMID 8145930.
- ^ Cornblath DR, Kurland LT, Boylan KB, Morrison L, Radhakrishnan K, Montgomery M. (November 1993). "Conjugal amyotrophic lateral sclerosis: report of a young married couple". Neurology 43 (11): 2378–80. PMID 8232960.
- ^ Corcia P, Jafari-Schluep HF, Lardillier D, Mazyad H, Giraud P, Clavelou P, Pouget J, Camu W (November 2003). "A clustering of conjugal amyotrophic lateral sclerosis in southeastern France". Neurol. 60 (4): 553–7. DOI:10.1001/archneur.60.4.553. PMID 12707069.
- ^ Tyler HR, Shefner J. Amyotrophic lateral sclerosis. Handb Clin Neurol. 1991;15:169-215. Serial publication.
- ^ Rowland LP (March 2001). "How amyotrophic lateral sclerosis got its name: the clinical-pathologic genius of Jean-Martin Charcot". Arch. Neurol. 58 (3): 512–5. DOI:10.1001/archneur.58.3.512. PMID 11255459. http://archneur.ama-assn.org/cgi/content/extract/58/3/512.
- ^ "Farewell Speech". lougehrig.com. July 4, 1939. Archived from the original on 12 April 2008. http://www.lougehrig.com/about/speech.htm. Retrieved April 16, 2008.
- ^ Abramova NA et al. Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death induced by methylpyridinium ion or beta amyloid peptide in SH-SY5Y neuroblastoma. J Neurosci Res. 2002 Feb 15;67(4):494-500.
- ^ Gribkoff V and Bozik M. KNS-760704 [(6R)-4,5,6,7-tetrahydro-N6-propyl-2, 6-benzothiazole-diamine dihydrochloride monohydrate] for the treatment of amyotrophic lateral sclerosis. CNS Neurosci Ther. 2008 Fall;14(3):215-26.
- ^ http://journals.lww.com/neurotodayonline/Fulltext/2010/07010/New_Als_Drug_Shows_Dose_Dependent_Efficacy_in.2.aspx
- ^ Cudkowicz M., et al. (2011). "The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis". Nature Medicine 17: 1652–1656.
- ^ http://clinicaltrials.gov/ct2/show/NCT00696332?term=ALS&rank=2
Further reading
- "ALS Hope Foundation". Archived from the original on 12 May 2008. http://www.alshopefoundation.org/. Retrieved 2008-06-21. "Dedicated to the care and cure of people with Lou Gehrig's Disease. (from site page us.php)"
- "Lou Gehrig: The Official Web Site". CMG Worldwide. Archived from the original on 9 May 2008. http://www.lougehrig.com. Retrieved 2008-06-21. "The Official Web site of Lou Gehrig is an informational Web site intended to honor the life, the legend and the career of Lou Gehrig. (from site page siteinfo/index.htm)"
- Patrick Aebischer; Ann C. Kato (November 2007). "Playing defense against Lou Gehrig's Disease" (Paper). Scientific American (Verlagsgruppe Georg von Holtzbrinck): pp. 86–93. http://www.sciam.com/article.cfm?id=playing-defense-against-l. Retrieved 2008-06-21. "Researchers have proposed potential therapies for a paralyzing disorder once thought to be untreatable (sub-title)"
External links
- Medline Plus article on ALS
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UpToDate Contents
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- 1. 筋萎縮性側索硬化症およびその他の運動ニューロン疾患の臨床的特徴 clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease
- 2. 筋萎縮性側索硬化症およびその他の運動ニューロン疾患の診断 diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease
- 3. 筋萎縮性側索硬化症の疫学および病因 epidemiology and pathogenesis of amyotrophic lateral sclerosis
- 4. 筋萎縮性側索硬化症の病態修飾療法 disease modifying treatment of amyotrophic lateral sclerosis
- 5. 家族性筋萎縮性側索硬化症 familial amyotrophic lateral sclerosis
English Journal
- Viral vectors for gene delivery to the central nervous system.
- Lentz TB, Gray SJ, Samulski RJ.AbstractThe potential benefits of gene therapy for neurological diseases such as Parkinson's, Amyotrophic Lateral Sclerosis (ALS), Epilepsy, and Alzheimer's are enormous. Even a delay in the onset of severe symptoms would be invaluable to patients suffering from these and other diseases. Significant effort has been placed in developing vectors capable of delivering therapeutic genes to the CNS in order to treat neurological disorders. At the forefront of potential vectors, viral systems have evolved to efficiently deliver their genetic material to a cell. The biology of different viruses offers unique solutions to the challenges of gene therapy, such as cell targeting, transgene expression and vector production. It is important to consider the natural biology of a vector when deciding whether it will be the most effective for a specific therapeutic function. In this review, we outline desired features of the ideal vector for gene delivery to the CNS and discuss how well available viral vectors compare to this model. Adeno-associated virus, retrovirus, adenovirus and herpesvirus vectors are covered. Focus is placed on features of the natural biology that have made these viruses effective tools for gene delivery with emphasis on their application in the CNS. Our goal is to provide insight into features of the optimal vector and which viral vectors can provide these features.
- Neurobiology of disease.Neurobiol Dis.2012 Nov;48(2):179-88. Epub 2011 Oct 7.
- The potential benefits of gene therapy for neurological diseases such as Parkinson's, Amyotrophic Lateral Sclerosis (ALS), Epilepsy, and Alzheimer's are enormous. Even a delay in the onset of severe symptoms would be invaluable to patients suffering from these and other diseases. Significant effort
- PMID 22001604
- Gene therapy for amyotrophic lateral sclerosis.
- Federici T, Boulis NM.AbstractGene therapy continues to be a potential option for amyotrophic lateral sclerosis (ALS). This chapter will inform the reader about promising therapeutic transgenes and proof-of-principle studies in transgenic rodent models of ALS. Challenges regarding the disease targets and time for therapeutic intervention will be also discussed. Finally, restorative therapy for ALS, as well as gene therapy for other motor neuron diseases will be briefly reviewed.
- Neurobiology of disease.Neurobiol Dis.2012 Nov;48(2):236-42. Epub 2011 Aug 25.
- Gene therapy continues to be a potential option for amyotrophic lateral sclerosis (ALS). This chapter will inform the reader about promising therapeutic transgenes and proof-of-principle studies in transgenic rodent models of ALS. Challenges regarding the disease targets and time for therapeutic int
- PMID 21889591
Japanese Journal
- ロクロニウムの至適投与量決定に筋弛緩モニタリング装置が有用であった筋萎縮性側索硬化症患者の麻酔経験
- 脇本 将寛,永田 博文,熊谷 基 [他]
- 麻酔 61(6), 599-601, 2012-06
- NAID 40019341783
- 愛知県下筋萎縮性側索硬化症患者の在宅療養実態に関する検討
- 市川 由布子,角田 由華,西川 智子 [他]
- 臨床神経学 52(5), 320-328, 2012-05
- NAID 40019325344
Related Links
- 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 ...
- Symptoms, diagnosis, treatment, and research on ALS, motor neuron disease, or Lou Gehrig's disease from the National Institute of Neurological Disorders and Stroke.
Related Pictures
★リンクテーブル★
| リンク元 | 「筋萎縮性側索硬化症」「筋萎縮性」 |
| 拡張検索 | 「familial amyotrophic lateral sclerosis」「amyotrophic lateral sclerosis」 |
「筋萎縮性側索硬化症」
- amyotrophic
- 英
- amyotrophic lateral sclerosis, ALS
- 同
- シャルコー病 Charcot disease、ゲーリック病、Gehrig病 Gehrig's disease、ルー・ゲーリック病 Lou Gehrig病 Lou Gehrig's disease
- 関
- 運動ニューロン疾患
まとめ
- 上位運動ニューロンと下位ニューロンが障害される運動ニューロン疾患の一つである。多くが孤発性であるが、5-10%に家族性の発症が見られ、発症年齢は20歳と若いが、進行は緩徐である。通常は、40歳以降の発症、特に50歳代が多い。下位ニューロンの障害が先行する。一側上肢遠位の筋萎縮で始まり対側上肢、両下肢に筋萎縮が進行し、球麻痺の出現、呼吸筋萎縮に至る。下位ニューロンの障害により、舌の線維束性攣縮、四肢筋の脱力、萎縮、線維性攣縮(これらは上肢優位、遠位筋優位)、また腱反射消失が見られる。また、上位ニューロンの障害により構音障害、嚥下障害、舌運動障害が認められ、下顎反射亢進が認められる。四肢では痙縮が下肢優位にまた、腱反射の亢進と病的反射が認められる。自律神経、感覚神経、脳の高次機能は障害されないため、他覚的感覚障害、眼球運動障害、膀胱・直腸障害、小脳徴候、錐体外路徴候、認知症、褥瘡は認められない。根治療法はなく、リルゾールでの延命治療、対症療法として、嚥下障害に対して経管栄養、呼吸障害に対して人工呼吸器を用いる。(BET.440)
概念
- 軸索変性をきたす神経変性疾患
- 誘発筋電図上ではM波の振幅の減衰が見られる
- 上位運動ニューロンと下位運動ニューロンが侵される。四肢、呼吸筋が侵される。ついには球麻痺をきたす。
- 自律神経、感覚神経、脳の高次機能は障害されない → (筋萎縮性側索硬化症の陰性症状) (1) 他覚的感覚障害、(2) 眼球運動障害、(3) 膀胱・直腸障害、(4) 小脳徴候、(5) 錐体外路徴候、(6) 認知症、(7) 褥瘡
疫学
- 有病率：4-6人/10万人
- 男女比=1.3:1 (YN.J-130)
- 発症年齢：中年以降。40歳以降でみられ、多くは50歳以降
- 日本では紀伊半島、米国ではグアムで多く見られる。
病因
- 孤発性：90%以上
- 遺伝性：5-10%
病理
- Lwey body-like hyaline inclusions, Hirano bodies, ブニナ体, slein-like inclusions
症状
| 症状 | 上肢 | 下肢 | ||
| 脊髄神経 | 上位運動ニューロン | 錐体路症状(痙性麻痺、腱反射亢進、バビンスキー徴候陽性) | 優勢 | |
| 下位運動ニューロン | 筋力低下、線維束性収縮、筋萎縮、呼吸障害 | 優勢 | ||
| 脳神経 | 上位運動ニューロン | 偽性球麻痺 | ||
| 下位運動ニューロン | 球麻痺(構音障害、嚥下障害、舌の萎縮・線維束性収縮)、顔面神経麻痺 | |||
検査
- 軸索変性を来すので、神経伝導速度の低下は顕著ではない → 筋電図で神経原性変化を見る！！
鑑別診断
- 変形性頚椎症：知覚障害が出現するので鑑別されるが、症状が神経所見がはっきり分からず、診断に難渋することがある、らしい。
| 腱反射 | 病的反射 | クレアチンキナーゼ | 神経伝導検査 | 筋電図 | |
| 筋萎縮性側索硬化症 | ↑↑ | ＋ | 軽度高値 | 正常 | 神経原性変化 |
| 重症筋無力症 | → | － | 正常 | 正常 | waning |
| 多発性筋炎 | → | － | 著明高値 | 正常 | 筋原性変化 |
| ギラン・バレー症候群 | ↓ | － | 正常 | 脱髄/ブロック | 神経原性変化 |
国試
「筋萎縮性」
- 英
- amyotrophic
- 関
- 筋萎縮
「familial amyotrophic lateral sclerosis」
- 関
- FALS