Multiple+Sclerosis

= Multiple Sclerosis =

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Multiple Sclerosis (MS) is a degenerative disease of the central nervous system (CNS). The cause of degeneration is not fully understood, but inflammation and the body's immune response play large roles. MS is characterized by inflammation and deterioration of the myelin sheaths that provide insulation to the axons found in the brain, spinal cord, and optic nerves [1,7]. This destruction of myelin results in lesions throughout the CNS, which is why the disease got its name meaning "multiple scars". The symptoms of MS vary greatly between individuals depending upon the locations and severity of the lesions. =====

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Myelin is found surrounding the axons of most neurons in both the central and the peripheral nervous systems [7]. It is composed of lipids and proteins that act as insulation, allowing a signal to pass down the axon more quickly and efficiently. Between each myelin sheath, the axon is exposed at areas called nodes of Ranvier. During saltatory conduction, the action potential that is initially propagated at the axon hillock travels through the internodal myelinated region to the first node. At this node, voltage gated sodium ion channels are opened, allowing for an influx of sodium. This influx renews the action potential, making the voltage change strong enough to travel to the next node along the axon where a subsequent influx of sodium takes place. This "leaping" from node to node continues along the length of the axon, allowing for the transmittance of an action potential. =====

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For individuals with MS, the myelin sheaths of the central nervous system, which are produced by cells called oligodendrocytes, are destroyed as a result of an immune reaction. When the myelin is destroyed, areas of the axon other than the nodes of Ranvier are initially exposed and are later covered over with scar tissue. Saltatory conduction is unable to occur as it should because internodal areas, which are normally insulated, have lost that insulation and are exposed. These newly exposed areas are also unable to aid in the renewal of the action potential because there are no ion channels in these internodal regions. Because of the loss of insulation, the transduction of the action potential is much slower than usual and the axon itself is much more susceptible to damage. Eventually, after attempting to pass along signal without the help of myelin sheaths, the axon becomes damaged enough that scar tissue forms where the myelin used to be. This scar tissue hinders the passage of the signal even further, sometimes completely preventing it from =====

reaching the terminal ending of axon. [2]
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The question of “which came first, the degeneration or the inflammation?” has not been definitively answered at this point [7]. Researchers have developed two opposing theories in attempts at finding the answer. The first, known as the inside-out model, claims that cytodegeneration initiates the immune response that characterizes MS [3]. The outside-in model, on the other hand, argues for the reverse. This model theorizes that inflammation leads to an immune response, causing the body to attack its own myelin, leading to cytodegeneration. [3] =====

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Regardless of what initiates this disease, it is known that the deterioration of the myelin, and eventually the axons themselves, disrupts the pathway that an action potential would typically follow [8]. Because of this, signals between the central and peripheral nervous systems may be hindered in reaching their destination. This interruption leads to the various symptoms of MS, which include: =====



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It has been found that the incidence of MS is low near the equator, but gradually increases with distance. It has been hypothesized that the amount of sun exposure and resulting vitamin D levels may play a role in the disease. Since regions farther north and south of the equator receive minimal sunlight for most of the year, the average vitamin D levels for people living in those regions are also lower. This is detrimental to a person's health for many reasons, but the most relevant to MS is vitamin D's role in regulating the immune system. One study found that individuals with MS have overall low levels of vitamin D. A correlation between low levels of vitamin D preceding high lesion activity and high levels of vitamin D prefacing low lesion activity [4]. This same study used data from two large prospective cohorts to determine if high vitamin D intake could reduce the risk of MS. A 40% reduction in risk of MS was found among women who ingested supplemental vitamin D compared to women who did not use supplements [4]. Although these findings are not definitive, further studies could prove that vitamin D deficiency plays a major role in the development and onset of multiple sclerosis. =====

__**Treatments**__

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There is no cure for MS, but medication can be used to manage the symptoms. These medications are sometimes able to modify the course of the disease, treat attacks, and improve function and safety [1]. Physical therapists can also aid in maintaining strength and stretching muscles, while occupational therapists can teach new strategies for going about everyday tasks [7]. Emotional support from family and friends, as well as a professional, may also be helpful in coping with the disease. =====

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Multiple sclerosis is not isolated to specific pathways withing the CNS. Lesions can form anywhere within the brain or spinal cord. Because of this, MS manifests in a very broad range of symptoms, including visual, somatosensory, and motor deficits. =====

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Optic neuritis, or inflammation of the optic nerve, is a common indicator of a person being at risk for developing MS. It occurs in acute attacks lasting approximately 30 days. In the first 10 days, the individual experiences gradual loss of vision and onset of pain during eye movement. Once the level of impairment stabilizes, however, it is typical for recovery to begin within 30 days. Many MS patients with optic neuritis also experience positive visual symptoms, including flashing lights and seeing colors, during recovery. Those who experience acute optic neuritis most often regain their vision without a problem. [5] =====

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It is often perplexing as to why MS causes visual impairments because the eyes are not part of the central nervous system [5]. It is important to remember, however, that they eyes are only just the beginning of vision. Once the light enters the eye and the image is projected onto the retina, the eye's role in vision is complete. Processing and conscious awareness of the image take place within the brain. Depending upon the visual stimulus, the signal will either follow the dorsal or ventral pathway to the visual cortex in the occipital lobe. =====



Somatosensory deficits are caused by lesions in the somatosensory cortices, where integration and processing of sensory information takes place:

 * ===== Primary Somatosensory Cortex =====
 * =====Secondary Somatosensory Cortex =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Sensory Association Area =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Multimodal Association Area [2] =====

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<span style="font-family: Verdana,Geneva,sans-serif;">The ascending pathways that carry the information, which are located in the dorsal and lateral regions of the spinal cord, may also be affected. These pathways include: =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Dorsal Column Medial Lemniscal (DCML) Pathway - relays information about proprioception and some aspects of touch =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;"> Anterolateral Pathway - carries information about both fast and slow pain =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Spinocerebellar Pathway - sends signals regarding proprioception [2] =====

<span style="font-family: Verdana,Geneva,sans-serif;">Similarly, motor deficits are caused by lesions in the motor cortices, where the planning and execution of movement takes place:

 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Primary Motor Cortex =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Premotor Cortex =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Supplementary Motor Area =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Frontal Eye Fields =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Visuomotor [2] =====

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<span style="font-family: Verdana,Geneva,sans-serif;">The descending pathways that care the motor commands, which are located in the ventral, medial, and lateral portions of the spinal cord, may also be affected. These pathways include: =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Lateral and Ventral Corticospinal Tracts - voluntary movements =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Rubrospinal Tract - flexion of upper limbs =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Tectospinal Tract - coordination of head and eye movement =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Pontine and Medullary Reticulospinal Tracts - aid in rhythmic movements such as locomotion =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">Lateral and Medial Vestibulospinal Tracts - vestibular reflexes, balance [2] =====



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<span style="font-family: Verdana,Geneva,sans-serif;">The most prevalent form of multiple sclerosis, relapsing-remitting MS (RRMS), affects roughly 85% of newly diagnosed patients. It is twice as likely to affect women than men and the average age of onset is 30 years. RRMS is characterized by periods of neurological symptoms as a result of lesion formation and inflammation lasting anywhere from weeks to months followed by periods of remission. During remission, the person can either make a substantial recovery or suffer from chronic disability as a result of the attacks. [3,6,10] =====

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<span style="font-family: Verdana,Geneva,sans-serif;">Within 10 years of initial diagnosis, the majority of individuals with RRMS will transition into secondary progressive MS (SPMS). SPMS is characterized by slowly progressing neurological deficit and CNS damage. Although acute attacks may occur with SPMS, they are less frequent and the individual is less likely to make a recovery following the attacks. Worsening function and progressive disability are seen both during and between attacks. [3,6,10] =====

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<span style="font-family: Verdana,Geneva,sans-serif;">Roughly 10% of individuals will be diagnosed with primary progressive MS (PPMS) at the onset of the disease. PPMS is characterized by steady progression of the disease and disability from the onset. Inflammation and acute attacks are not typical for an individual with PPMS, but temporary periods of remission or recovery can be seen. [3,6,10] =====

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<span style="font-family: Verdana,Geneva,sans-serif;">The least common form, progressive-relapsing MS (PRMS), appears in 5% of individuals diagnosed with MS. PRMS is characterized by a steady progression of disability scattered with acute inflammatory attacks. [3,6,10] =====

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<span style="font-family: Verdana,Geneva,sans-serif;">Multiple Sclerosis is a demyelinating immune-mediated disorder with no known cause or cure. It is very unpredictable and can follow various courses of progression. It manifests in incredible diverse neurological symptoms, leading to a wide range of ability. Research continues to be done in an effort to discover a cure for this debilitating disease. In the meantime, it is important for individuals with MS and their loved ones to keep fighting for a cure. =====

<span style="font-family: Verdana,Geneva,sans-serif;">Glossary

 * =====<span style="font-family: Verdana,Geneva,sans-serif;">lesion - a region in an organ or tissue that has suffered damage through injury or disease; area at which demyelination has taken place =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">autoimmune - immune system attacks normally occurring antigens in the body, not proven to occur in MS =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">immune-mediated disease - the immune system attacks the body (myelin), but no normal antigen has been found to cause the attacks =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">central nervous system - brain, spinal cord, and optic nerves =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">myelin - fatty sheath surrounding the axon of a neuron =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">oligodendrocytes - cells that produce the myelin found in the CNS =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">cytodegeneration - break down of cells that causes the release of antigens =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">saltatory conduction - movement of an action potential down an axon, passing from one Node of Ranvier to the next =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">remission - reduction in severity of the disease =====
 * =====<span style="font-family: Verdana,Geneva,sans-serif;">somatosensory - the detection of any sensation on/in the body =====

__**<span style="font-family: Verdana,Geneva,sans-serif;">True/False - if false, provide correction **__

 * 1) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** Schwann cells form the myelin in the central nervous system. =====
 * 2) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** The most prevalent type of MS is relapsing-remitting. =====
 * 3) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** High levels of vitamin D have been implicated in causing MS. =====
 * 4) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** There is a definitive cause of MS. =====
 * 5) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** There are 4 main forms of MS. =====
 * 6) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** The DCML is a somatosensory pathway. =====
 * 7) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** The tectospinal pathway carries motor commands. =====
 * 8) =====<span style="font-family: Verdana,Geneva,sans-serif;">**T/F** Primary progressive is the least common form of MS. =====

__**<span style="font-family: Verdana,Geneva,sans-serif;">Short Answer **__
 * 1) =====<span style="font-family: Verdana,Geneva,sans-serif;">Describe saltatory conduction. Why is it unable to occur in certain neurons in people with MS? =====
 * 2) =====<span style="font-family: Verdana,Geneva,sans-serif;">What is the most common indicator of MS? Why is this unexpected? =====
 * 3) =====<span style="font-family: Verdana,Geneva,sans-serif;">Why is MS incurable as of right now? =====

<span style="font-family: Verdana,Geneva,sans-serif;">Suggested Reading
<span style="font-family: Verdana,Geneva,sans-serif;">Breakthrough offers first direct measurement of spinal cord myelin in multiple sclerosis

National MS Society

**__<span style="font-family: Verdana,Geneva,sans-serif;">True/False __**

 * 1) =====<span style="font-family: Verdana,Geneva,sans-serif;">F - Oligodendrocytes are found in the CNS, Schwann cells are in the peripheral nervous system (PNS) =====
 * 2) =====<span style="font-family: Verdana,Geneva,sans-serif;">T =====
 * 3) =====<span style="font-family: Verdana,Geneva,sans-serif;">F - Low levels are implicated in causing MS, higher levels have been shown to decrease risk =====
 * 4) =====<span style="font-family: Verdana,Geneva,sans-serif;">F - The cause of the immune attacks that lead to MS is still unknown =====
 * 5) =====<span style="font-family: Verdana,Geneva,sans-serif;">T =====
 * 6) =====<span style="font-family: Verdana,Geneva,sans-serif;">T =====
 * 7) =====<span style="font-family: Verdana,Geneva,sans-serif;">T =====
 * 8) =====<span style="font-family: Verdana,Geneva,sans-serif;">F - Progressive-relapsing is the least common form =====

<span style="font-family: Verdana,Geneva,sans-serif;">__**Short Answer**__
 * 1) =====<span style="font-family: Verdana,Geneva,sans-serif;">Action potential travels down axon from leaping from one node of Ranvier to the next. It is able to reach the next node because the insulation provided by the myelin. Saltatory conduction is impaired in individuals with MS because they myelin has degenerated so the action potential is unable to reach the next node. =====
 * 2) =====<span style="font-family: Verdana,Geneva,sans-serif;">Optic neuritis - it is unexpected because the optic tract is often not thought of as being a part of the central nervous system. =====
 * 3) =====<span style="font-family: Verdana,Geneva,sans-serif;">MS is incurable because there is no known cause, therefore, it cannot be prevented or cured. =====

<span style="font-family: Verdana,Geneva,sans-serif;">References

 * 1) =====<span style="font-family: Verdana,Geneva,sans-serif;">National Multiple Sclerosis Society. (n.d.). About ms. Retrieved from http://www.nationalmssociety.org/about-multiple-sclerosis/index.aspx =====
 * 2) =====<span style="font-family: Verdana,Geneva,sans-serif;">Neurophysiological Basis of Movement class notes =====
 * 3) =====<span style="font-family: Verdana,Geneva,sans-serif;">Stys, P. K., Zamponi, G. W., van Minnen , J., & Geurts, J. J. G. (2012). Will the real multiple sclerosis please stand up?. Nature, 13, 507-515. =====
 * 4) =====<span style="font-family: Verdana,Geneva,sans-serif;">Munger, K. L., Zhang, S. M., O'Reilly, E., Hernan, M. A., Olek, M. J., Willett, W. C., & Ascherio, A. (2004). Vitamin d intake and incidence of multiple sclerosis. Neurology, 62, 60-65. =====
 * 5) =====<span style="font-family: Verdana,Geneva,sans-serif;">Atkins, E. J. (2009). Optic neuritis and ms. Retrieved from http://www.msfocus.org/article-details.aspx?articleID=380 =====
 * 6) =====<span style="font-family: Verdana,Geneva,sans-serif;">Multiple Sclerosis Association of America. (2013, November 20). Ms overview. Retrieved from http://www.mymsaa.org/about-ms/overview/ =====
 * 7) =====<span style="font-family: Verdana,Geneva,sans-serif;">Mayo Clinic. (2012, December 15). Multiple sclerosis . Retrieved from http://www.mayoclinic.com/health/multiple-sclerosis/DS00188 =====
 * 8) =====<span style="font-family: Verdana,Geneva,sans-serif;">Steinman, L. (2001). Multiple sclerosis: A two stage disease. Nature Immunology, 2, 762-764. Retrieved from http://www.mult-sclerosis.org/news/Sep2001/MSTwoStageDisease.html =====
 * 9) =====<span style="font-family: Verdana,Geneva,sans-serif;">Lassmann, H. (2013). Relapsing-remitting and primary progressing ms have the same cause(s) - the neuropathologist's view: 1. Multiple Sclerosis Journal, 19(3), 266-267. =====
 * 10) =====<span style="font-family: Verdana,Geneva,sans-serif;">Polman, C. H., et al. (2011). Diagnosis criteria for multiple sclerosis: 2010 revisions to the mcdonald criteria. Annals of Neurology, 69(2), 292-302. =====