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Multiple sclerosis

A healthy neuron with myelin sheath around the long, thin axon.
Symptoms of multiple sclerosis

Multiple sclerosis (MS) is a serious health condition that gets worse over time. In this disease, the body’s natural guard against illness (the immune system) damages fatty coverings called myelin sheaths around the nerve cells (neurons) in the central nervous system (CNS).[1] The disease has different effects in different people, and can make people’s bodies, eyesight, speech, and minds work poorly.[2] People with MS do not normally live as long as healthy people.[1]

In healthy people, myelin sheaths help neurons work.[3] Electric signals in neurons move quickly through long, narrow axons like electricity in a wire.[3] The myelin is like the insulator around the wire that keeps the signal strong by keeping it from moving out of the wire before the end.[3] In people with MS, infiltration of immune cells causes inflammation within the CNS resulting in the loss of the protective insulator, called "demyelination." The progressive loss of the myelin sheath, as well as the loss of myelin-producing cells, impair the ability of the body to regrow its myelin.[2] Without the protective covering, the signals between neurons do not travel well.[2] Because of this, the mind and body cannot work like they normally do.[2]

Possible causes

Scientists and doctors do not know for certain the cause of MS, but they think some things put some people at a higher risk for MS:[2]

Research about the causes of MS is still incomplete. Some scientists think that a relatively unknown pathogen called Chlamydia pneumoniae may cause MS.[8][9] Also, some viruses can cause myelin damage, there are other viruses that have been shown to make people more likely to get MS.[1][8][10] Even though scientists and doctors have theories, no one has found one cause that explains every case of the disease.

Symptoms

 
Four graphs showing how the severity of MS symptoms can increase and decrease in different ways over time.

Quite a few forms of MS exist, which can create difficulty in deciding how to manage the illness.[11] The disease damages myelin. Sometimes, the body can do limited repairs to myelin. When this happens, symptoms (the problems caused by the disease) go away for a short time. This is called remission.[12] When the body attacks the myelin again, the symptoms return and this is called relapse.[12] The type of MS that has remissions and relapses is called Remitting-Relapsing MS.[11] In less common cases, the body continues attacking myelin and the symptoms get worse rapidly, a form called "Primary Progressive MS".[11] Sometimes a combination of the two types of disease can occur simultaneously.[11]

People with MS have many problems. Their muscles are usually weak, they may shake uncontrollably, they have trouble moving, and they have trouble balancing. People with MS often feel a great amount of pain and tire easily. Their speech and sight sometimes become very poor. Thinking and solving problems is more difficult for people with MS than for healthy people.[1]

Inside the body, MS causes damage that cannot be seen or measured without special medical equipment. The immune system attacks either the fatty parts of the myelin or the protein parts of the myelin.[2][13] The body may also attack the cells that produce the myelin sheath, called glial cells.[2] When myelin is damaged or missing, large areas of axons affected by the damage are visible as scars or lesions in the central nervous system tissue that build up with repeated repair attempts by the body over time.[2] Lesions appear in different areas of the central nervous system depending on what form of MS a person has.[14]

Inflammation is an important part of MS symptoms. Inflammation occurs whenever an injury or illness is detected by the body. It is the first part of an immune system response. In MS patients, inflammation against myelin causes swelling and other harmful effects in the nervous system.[2] Inflammation can happen due to infection by Chlamydia Pneumoniae.

People with MS

The people who get MS are usually between 20 and 40 years old, although it can happen to older or, very rarely, younger people too.[1] MS is significantly more common in areas of the world that are far away from the equator.[1][15] Areas far from the equator get less sunlight than areas near the equator, and the human body requires sunlight to make vitamin D for itself. This observation supports the idea that MS is caused partly by too little vitamin D. People who move from one part of the world to another when they are children are more likely to develop MS than people who do not move long distances until later in life or who never move long distances.[1][5]

Diagnosis

To diagnose MS, or to tell if a person has it, a doctor will determine what kind of symptoms are present and how often they occur. The most common guidelines used for this are called the McDonald criteria, which define the symptoms of MS and how often they must occur in order to make a diagnosis.[1] A doctor can also order tests to be done by a laboratory, which can determine how active the immune system is in the patient.[16][17] A special machine called an MRI can photograph the inside of the central nervous system to show if the person has lesions from damaged myelin.[16][18] Certain types of neurons can be checked to see how responsive they are. Neurons with damaged myelin around their axons will respond more slowly than normal neurons.[19]

Treatment

Once a person is diagnosed with MS, a doctor can help ease the symptoms. Scientists have not yet found a way to cure MS, or take it away entirely. The form of MS that comes and goes regularly can be treated more easily than other forms.[20] Some treatments are used only during attacks to make the attacks easier on the patient or to help recovery after the attacks are over.[1][21] Other treatments are used all the time to help make attacks happen less often. These kinds of treatments are usually injections or infusions directly into veins, but newer treatments can be taken daily by mouth instead.[22][23][24][25][26] Some people seek other treatments outside of usual medicine, but these have not been shown in scientific studies to be effective.[27]

Multiple Sclerosis Media

  • HLA region of chromosome 6: Changes in this area increase the probability of getting MS.

  • Multiple Sclerosis. See a full animation of this medical topic.

  • Demyelination in MS: On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated.

  • Animation showing dissemination of brain lesions in time and space as demonstrated by monthly MRI studies along a year

  • Multiple sclerosis as seen on MRI

  • Irritation zone after injection of glatiramer acetate.

  • Deaths from multiple sclerosis per million persons in 2012
         0     1     2     3–5     6–12     13–25

  • Detail of Carswell's drawing of MS lesions in the brain stem and spinal cord (1838)

  • Photographic study of locomotion of a woman with MS with walking difficulties created in 1887 by Muybridge

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Compston, Alastair; Coles, Alasdair (Oct 25, 2008). "Multiple sclerosis". Lancet. 372 (9648): 1502–17. doi:10.1016/S0140-6736(08)61620-7. PMID 18970977. S2CID 195686659.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Compston, Alastair; Coles, Alasdair (Apr 6, 2002). "Multiple sclerosis". Lancet. 359 (9313): 1221–31. doi:10.1016/S0140-6736(02)08220-X. PMID 11955556. S2CID 14207583.
  3. ↑ 3.0 3.1 3.2 al.], Neil R. Carlson ... [et (2010). Psychology : the science of behavior (7th ed.). Boston: Allyn & Bacon. ISBN 978-0-205-54786-9.
  4. ↑ Dyment, David A.; Ebers, George C.; Dessa Sadovnick, A. (Feb 2004). "Genetics of multiple sclerosis". Lancet Neurology. 3 (2): 104–10. doi:10.1016/s1474-4422(03)00663-x. PMID 14747002. S2CID 16707321.
  5. ↑ 5.0 5.1 5.2 Marrie, RA (Dec 2004). "Environmental risk factors in multiple sclerosis aetiology". Lancet Neurology. 3 (12): 709–18. doi:10.1016/S1474-4422(04)00933-0. PMID 15556803. S2CID 175786.
  6. ↑ 6.0 6.1 Ascherio, Alberto; Munger, Kassandra L. (Jun 2007). "Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors". Annals of Neurology. 61 (6): 504–13. doi:10.1002/ana.21141. PMID 17492755. S2CID 36999504.
  7. ↑ Ascherio, Alberto; Munger, Kassandra L.; Simon, K Claire (Jun 2010). "Vitamin D and multiple sclerosis". Lancet Neurology. 9 (6): 599–612. doi:10.1016/S1474-4422(10)70086-7. PMID 20494325. S2CID 12802790.
  8. ↑ 8.0 8.1 Ascherio, Alberto; Munger, Kassandra L. (Apr 2007). "Environmental risk factors for multiple sclerosis. Part I: the role of infection". Annals of Neurology. 61 (4): 288–99. doi:10.1002/ana.21117. PMID 17444504. S2CID 7682774.
  9. ↑ Kurtzke, JF (Oct 1993). "Epidemiologic evidence for multiple sclerosis as an infection". Clinical Microbiology Reviews. 6 (4): 382–427. doi:10.1128/CMR.6.4.382. PMC 358295. PMID 8269393.
  10. ↑ Gilden, DH (Mar 2005). "Infectious causes of multiple sclerosis". Lancet Neurology. 4 (3): 195–202. doi:10.1016/S1474-4422(05)01017-3. PMC 7129502. PMID 15721830.
  11. ↑ 11.0 11.1 11.2 11.3 Lublin, F. D.; Reingold, S. C. (Apr 1996). "Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis". Neurology. 46 (4): 907–11. doi:10.1212/wnl.46.4.907. PMID 8780061. S2CID 40213123.
  12. ↑ 12.0 12.1 Bramow, Stephan; Frischer, Josa M.; Lassmann, Hans; Koch-Henriksen, Nils; Lucchinetti, Claudia F.; Sørensen, Per S.; Laursen, Henning (20 September 2010). "Demyelination versus remyelination in progressive multiple sclerosis". Brain. 133 (10): 2983–2998. doi:10.1093/brain/awq250. PMID 20855416.
  13. ↑ Ho, Peggy P.; Kanter, Jennifer L.; Johnson, Amanda M.; Srinagesh, Hrishikesh K.; Chang, Eun-Ju; Purdy, Timothy M.; Van Haren, Keith; Wikoff, William R.; Kind, Tobias; Khademi, Mohsen; Matloff, Laura Y.; Narayana, Sirisha; Hur, Eun Mi; Lindstrom, Tamsin M.; He, Zhigang; Fiehn, Oliver; Olsson, Tomas; Han, Xianlin; Han, May H.; Steinman, Lawrence; Robinson, William H. (2012). "Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation". Science Translational Medicine. 4 (137): 137–73. doi:10.1126/scitranslmed.3003831. PMC 3953135. PMID 22674551.
  14. ↑ Pittock, S. J.; Lucchinetti, C. F. (Mar 2007). "The pathology of MS: new insights and potential clinical applications". The Neurologist. 13 (2): 45–56. doi:10.1097/01.nrl.0000253065.31662.37. PMID 17351524. S2CID 2993523.
  15. ↑ Alonso, A.; Hernan, M. A. (Jul 8, 2008). "Temporal trends in the incidence of multiple sclerosis: a systematic review". Neurology. 71 (2): 129–35. doi:10.1212/01.wnl.0000316802.35974.34. PMC 4109189. PMID 18606967.
  16. ↑ 16.0 16.1 McDonald, W. Ian; Compston, Alistair; Edan, Gilles; Goodkin, Donald; Hartung, Hans-Peter; Lublin, Fred D.; McFarland, Henry F.; Paty, Donald W.; Polman, Chris H.; Reingold, Stephen C.; Sandberg-Wollheim, Magnhild; Sibley, William; Thompson, Alan; Van Den Noort, Stanley; Weinshenker, Brian Y.; Wolinsky, Jerry S. (Jul 2001). "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis". Annals of Neurology. 50 (1): 121–7. doi:10.1002/ana.1032. PMID 11456302. S2CID 13870943.
  17. ↑ Link, Hans; Huang, Yu-Min (Nov 2006). "Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness". Journal of Neuroimmunology. 180 (1–2): 17–28. doi:10.1016/j.jneuroim.2006.07.006. PMID 16945427. S2CID 22724352.
  18. ↑ Rashid, Waqar; Miller, David (Feb 2008). "Recent advances in neuroimaging of multiple sclerosis". Seminars in Neurology. 28 (1): 46–55. doi:10.1055/s-2007-1019127. PMID 18256986.
  19. ↑ Gronseth, G. S.; Ashman, E. J. (May 9, 2000). "Practice parameter: the usefulness of evoked potentials in identifying clinically silent lesions in patients with suspected multiple sclerosis (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology". Neurology. 54 (9): 1720–5. doi:10.1212/wnl.54.9.1720. PMID 10802774. S2CID 9635808.
  20. ↑ Skrzipek, Sabine; Vogelgesang, Antje; Bröker, Barbara M.; Dressel, Alexander (24 October 2011). "Differential effects of interferon-ss1b on cytokine patterns of CD4+ and CD8+ T cells derived from RRMS and PPMS patients". Multiple Sclerosis Journal. 18 (5): 674–678. doi:10.1177/1352458511427317. PMID 22025329. S2CID 206698737.
  21. ↑ Burton, Jodie M.; O'Connor, Paul W.; Hohol, Marika; Beyene, Joseph (2012-12-12). "Oral versus intravenous steroids for treatment of relapses in multiple sclerosis". Cochrane Database of Systematic Reviews (Online). 12: CD006921. doi:10.1002/14651858.CD006921.pub3. PMID 23235634.
  22. ↑ "Natalizumab Injection". US National Library of Medicine (Medline). 2012-05-15. Retrieved 31 March 2013.
  23. ↑ Marriott, J. J.; Miyasaki, J. M.; Gronseth, G.; O'Connor, P. W.; Therapeutics Technology Assessment Subcommittee of the American Academy of Neurology (2010-05-04). "Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 74 (18): 1463–70. doi:10.1212/WNL.0b013e3181dc1ae0. PMC 2871006. PMID 20439849.
  24. ↑ Kappos, Ludwig; Bates, David; Edan, Gilles; Eraksoy, Mefkûre; Garcia-Merino, Antonio; Grigoriadis, Nikolaos; Hartung, Hans-Peter; Havrdová, Eva; Hillert, Jan; Hohlfeld, Reinhard; Kremenchutzky, Marcelo; Lyon-Caen, Olivier; Miller, Ariel; Pozzilli, Carlo; Ravnborg, Mads; Saida, Takahiko; Sindic, Christian; Vass, Karl; Clifford, David B.; Hauser, Stephen; Major, Eugene O.; O'Connor, Paul W.; Weiner, Howard L.; Clanet, Michel; Gold, Ralf; Hirsch, Hans H.; Radü, Ernst-Wilhelm; Sørensen, Per Soelberg; King, John (Aug 2011). "Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring". Lancet Neurology. 10 (8): 745–58. doi:10.1016/S1474-4422(11)70149-1. PMID 21777829. S2CID 15639613.
  25. ↑ "FDA approves new multiple sclerosis treatment (Press release)". US FDA. 12 September 2012. Retrieved 31 March 2013.
  26. ↑ "Gylenya medication guide" (PDF). Novartis Pharmaceuticals Corporation. May 2012. p. 2. Retrieved 31 March 2013.
  27. ↑ Olsen, SA (2009). "A review of complementary and alternative medicine (CAM) by people with multiple sclerosis". Occupational Therapy International. 16 (1): 57–70. doi:10.1002/oti.266. PMID 19222053.

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