Multiple+Sclerosis+V

= **//Multiple Sclerosis//** =

//Introduction //
toc Multiple Sclerosis is an immune-mediated disease or process that affects the myelin sheaths of neuronal cells within the central nervous system (brain and spinal cord) [1]. This occurs due abnormal behavior of the body's immune system, in which the immune system goes rogue and will attack the oligodendrocytes, myelin sheaths, and axons that the myelin covers within the central nervous system resulting in scar tissue or sclera in multiple areas. This is how multiple sclerosis got its' name. The distinguishing characteristic of MS (Multiple Sclerosis) is that it is symptomatically episodic in nature and each episode can occur months or even years apart from each other [9]. It also can attack anywhere within the CNS making it unpredictable exactly how one individual will be affected. media type="youtube" key="QpUMT-SA75Q" width="341" height="194" align="right" Because MS damages the CNS (central nervous system) and due to the CNS's overwhelming control of the body, function can be adversely effected and symptoms vary over a very wide range. Symptoms include but are not limited to: fatigue, cognitive difficulties, gait difficulties, spasticity, numbness, visual problems, vertigo, and dizziness [1].

The exact cause of MS is unknown because it attacks multiple and different central nervous system structures via a rogue immune system [1]. It is believed however that the cause could be due to underlying environmental, infectious, and/or genetic risk factors. This makes MS difficult to diagnose and the diagnosis procedure itself includes multiple tests. MS is found to be more common in individuals who live farther away from the equator, those who are of Northern European descent, those with a genetic and/or environmental predisposition, those with a family member who has MS, and if the individual is female then she is twice as likely to develop MS [5]. MS is also more likely to be found in individuals who have other illnesses or disease such as but not limited to: diabetes, thyroid disease, or herpes. MS has been shown to be most prevalent or start to affect one's life anywhere in the age range of 20 to 50 years old [9].

There are no cures for MS because we don't know what proteins the rogue immune system cells (T cells specifically) are attacking in the CNS. However, there are various treatments that can improve one's quality of life who has MS. Treatment can occur through medical routes such as using corticosteroids or utilizing plasmapheresis. It has been shown that improved quality of life can also occur by having a healthy diet and exercising daily. Various types of therapy (physical or occupational) have also been shown to improve one's quality of life who has MS. Even though MS can cause complications that affects an individuals' quality of life it doesn't severely affect one's life span. New research has shown that people with MS generally live about 7 years less than the rest of the population due to disease complications. As of 2016, there have been 2.5 million reported cases of MS worldwide and 400,000 of those cases are in the United States alone. Globally, the prevalence rate for MS is about 30 people per 100,000. Each week about 200 new cases of MS are reported and recorded.

//**Central Nervous System Anatomy **//
The Central Nervous system is made up of the brain and spinal cord. From superficial to deep the brain is surrounded by: the skull, meninges(includes the dura, arachnoid, and pia mater), cerebrospinal fluid, and the blood-brain barrier. The outside of the brain is lined with gyri and sulci and deep fissures which all contribute to an increased surface area. The brain is divided sagittally by a longitudinal fissure into left and right cerebral hemispheres and is further divided into 4 lobes: the parietal lobe, the frontal lobe, the occipital lobe, and the temporal lobe. The transverse cerebral fissure divides the cerebrum from the cerebellum. The central sulcus divides the pre-central gyrus (primary motor cortex) and the post-central gyrus (the primary somatosensory cortex). The brain has multiple structures that constitute it as well such as: the cerebellum which is inferior to the occipital lobe and posterior to the brain stem, the thalamus which lies on top of the hypothalamus, and the brain stem which is inferior to the hypothalamus and contains the midbrain, the pons, and the medulla. The brain also has four ventricles containing CSF which functions in providing nutrients and exchanging waste products. Furthermore, the brain is made up of gray and white matter. The cerebral cortex, which is the thin superficial layer of gray matter makes up 40% of the mass of the brain. Within the cerebral cortex are three types of functional areas: motor areas, sensory areas, and association areas. While the internal white matter makes up the other 60% and hosts various neural pathways. At the center of the cerebrum you will find the corpus callosum which connects the left and right cerebral hemispheres via axons crossing over. The Brain is connected to the spinal cord via the brain stem where many neural fibers pass through to synapse on nuclei within the cerebrum, brainstem, and cerebellum. For more information on the brain click [|here].

The Cerebellum is the other major structure within the CNS besides the spinal cord and cerebral cortex. As noted above, it's located inferiorly to the occipital lobe and posterior to the brain stem at the level of the pons. The cerebellum is split into two hemispheres by the vermis. It is then further divided into three lobes: the anterior, posterior, and flocculonodular lobe. The cerebellum is lined with folia which resemble gyri to increase surface area. It also has a outer gray matter and and inner white matter. It is connected to the brainstem via the cerebellar peduncles (a bundling of fibers).

The Spinal Cord begins at the level of the foramen magnum (base of the skull) and ends as the conus medullaris at the L1/L2 vertebra. It is divided to left and right halves by two lengthwise fissures: the ventral median fissure and the dorsal median sulcus. It provides two-way (ascending/descending) communication to and from the brain. It is separated into four different segments based on location: A cervical segment which has 7 cervical vertebrae, a thoracic segment which contains 12 vertebrae, a lumbar segment with 5 lumbar vertebrae, and a sacral segment with 5 sacral vertebrae. Within the spinal cord are 31 pairs of nerves which extend out of each vertebrae into the peripheral nervous system. The spinal cord is surrounded from superficial to deep by bone, meninges (dura, arachnoid, and pia mater) and cerebrospinal fluid. There are denticulate ligaments which are extensions of the pia mater that secure the spinal cord to the dura mater conferring increased protection. The Filum terminale, which lies at the inferior end of the spinal cord has fibrous extensions from the conus medullaris which anchors the spinal cord to the coccyx which also confers protection. The spinal cord is made up of gray and white matter just like the cerebrum. Within the gray matter you will find dorsal horns which contain interneurons that receive somatic and sensory input, ventral horns whose somatic motor neurons exit the cord via the ventral roots, lateral horns which are only found in the lumbar and thoracic segments of the spinal cord, and dorsal root ganglia which contain cel bodies of sensory neurons. The white matter within the spinal cord contains all the ascending and descending spinal tracts. The ascending spinal tracts consist of: the Dorsal column-medial lemniscal (DCML) pathways, the Spinothalamic pathways, and the Spinocerebellar tracts. The DCML and Spinothalamic tracts will terminate in the cerebral cortex while the spinocerebellar tracts will terminate in the cerebellum The descending spinal tracts consists of: the corticospinal tract, the reticulospinal tract, the tectospinal tract, the rubrospinal tract, and the vestibulospinal tract and will terminate on musculature, skin, organs, and joints via the peripheral neural axons.


 * Visual System:** The optic system is made up of the eyes and the structures within it, the nerves that innervates the ocular musculature, the neural tracts that process the information coming into the eyes, the various nuclei, and the occipital lobe or visual cortex.


 * Blood Brain Barrier:** The blood brain barrier is located within and surrounds the cerebrum. It is made up of continuous endothelium of capillary walls, a basal lamina, and feet of astrocytes which provide signals to the endothelium for the formation of tight junctions which aid in helping maintain a stable environment for the brain and separation of neurons from blood-borne substances.


 * Oligodendrocytes:** Oligodendrocytes are a type of neuroglia within the central nervous system. They provide support to neurons and and axons and insulate the axons as well. They have a central nucleus and projections that extend onto axons that form the myelin sheaths.

They conduct electrical impulses to other target cells such as other neurons and muscle cells.
 * axons:** Axons are long and thin projections that originate from a neuron cell body or soma.

surrounds axons and neural cells. These sheaths form an electrical insulating layer that surrounds the axons to increase speed of conduction [3]. In the central nervous system, myelin is made by oligodendrocytes while in the peripheral nervous system myelin is made by Schwann cells.
 * Myelin:** is a fatty white substance or sheath that

//Multiple Sclerosis' Effects on the Central Nervous System Structures //
Multiple Sclerosis affects everyone differently. This is due to MS being sporadic and unpredictable in nature. No two peoples symptoms are the same usually due to MS presenting or affecting different areas within each patient. Here, we will be describing what functions will be impaired depending on what area within the CNS is affected.

**__//Motor areas//__**
1. **Primary motor cortex**: Damage or sclerosis of the primary motor cortex will result in dysfunctions in precise, skilled, voluntary movements such as reaching for a pencil or picking up an object [24]. Depending on where the damage occurs, the dysfunction can occur anywhere within the body. It can even result in paralysis of the corresponding limb of the damaged area. In most cases though spasticity results.

2. **Premotor cortex**: Damage to the premotor cortex will result in dysfunctions in repetitious, or patterned motor skills such as walking or running [24]. It also will result in impairments of coordinated, sequential actions like throwing a ball. The premotor cortex is also involved in the planning of movements based on sensory feedback. So the effected individual may have problems in preparing for perturbations or reacting properly to perturbations in their environment

3. **Broca's area**: Broca's area functions in the movement of the tongue muscles and is active before one begins to speak. Thus, damage to Broca's area, would affect one's ability to speak. It also affects ones' ability to understand speech.

4. **Frontal eye fields**: Damage to the frontal eye fields would result in dysfunctions in eye movements which could include: nystagmus, optic neuritis, and a myriad of other eye conditions depending on how the damage occurred or where it took place within the frontal eye field itself [11].

5. **Supplementary Motor Areas**: The Supplementary Motor areas lies on top of the premotor cortex and anterior to the primary motor cortex. It's responsible for the preparation of movements in the proximal and axial musculature [24]. It also controls both the contralateral and ipsilateral muscles within the aforementioned sections of the body. The neurons here are activated before and after movement but not during the movement itself. Damage results in muscle weakness, postural instability, and speech problems to even speech arrest.

__**//Sensory areas//**__
1. **Primary somatosensory cortex**: The primary somatosensory cortex receives sensory information from the skin, skeletal muscles, and joints. It receives cutaneous input from Merkel's discs, Meisnner's Corpuscles, Raffini endings, and Pacinian Corpuscles and it receives musculature and proprioceptive input from the golgi tendon organs and muscle spindles within the joint capsules and musculature [24]. So depending on where within the somatosensory cortex the damage occurred, dysfunction of interpretation of sensory information will occur. An example of this would be that if the area that holds the hand somatotopically is affected. Cutaneous and proprioceptive information would not be processed or felt by the individual. They would not be able to tell if they had actually touched an object with their hand or not. They also would not be able to feel or perceive pain or temperature information coming from the hand.

2. **Somatosensory association cortex**: The somatosensory association cortex helps with the integration of sensory input which comes from the primary somatosensory cortex [24]. It helps determine the size, texture, and the individual characteristics that make up the object or item being perceived by an individual. Damage to this area would then affect how an individual perceives or feels an object. They would have a hard time distinguishing what something felt like. They may not be able to tell you if a ball feels smooth or if the surface of a rock is either smooth or bumpy and coarse for example because they are not able to process the information coming from the cutaneous receptors.

3. **Visual areas**: If damage to the visual cortex occurs due to sclerosis vision becomes impaired. It's primary role is the interpretation of incoming visual information [24]. The primary visual cortex innervates the retina of the eye. Depending on where the damage is within the visual cortex, it will be as though damage also occurred in the corresponding retinal area being innervated by said damaged area. Thus a local blindness occurs where you will have a spot of your visual field blacked out essentially.

4. The **visual association area** surrounds the primary visual cortex and helps interpret color, form, and movement of an object based on past visual experiences [24]. Damage to the visual association area will result in difficulty perceiving the shape of an object and bordered of that object, tracking an objects movement, and seeing changes in location of the object.

5. **Auditory areas**: The auditory areas are responsible for interpreting information coming from the inner ear. This information includes pitch, loudness, and location of a sound. If damage occurs on the primary auditory cortex then partial or even complete deafness can occur. If damage to the auditory association area occurs then interpretation and memory of a sound will be lost.

6. **Olfactory cortex**: The olfactory cortex is responsible for the perception of smells and odors. Damage here then would influence ones' ability to recognize or interpret something they smell.

7. **Gustatory cortex**: The gustatory cortex is responsible for perceiving what we taste so damage here would result in a loss of the perception of taste.

8. **Visceral Sensory cortex**: The visceral sensory cortex is responsible for helping us feel if we have a full stomach or a full bladder. Damage here then would result in the loss of sensation of these feelings.

9. **Vestibular cortex**: Damage to the vestibular cortex can impair movement drastically. The vestibular cortex is responsible for awareness of balance and determining where our head is in space.

__**//Multimodal Association areas//**__
The multimodal association areas are responsible for reaching and sending output to and from multiple sensory areas. It also sends information to the premotor cortex. The multimodal association areas perceive information and store it into our memories so we are able to compare the information we receive with a past experience or with a future experience [24]. The areas give meaning to information which allows us to decide on a course of action to take in response to whatever we may perceive. There are three sectors that make up the multimodal association areas: the Anterior and posterior association area, and the Limbic area.

1. **Anterior association area**: The anterior association area functions in intelligence, cognition, recall, and personality [24]. It holds the structures used for working memory needed for judgement, reasoning, persistence, and conscience - Pearson. Thus damage here would result in misjudgments, an inability to remember, and difficulty in reasoning. 2. **Posterior association area**: The posterior association area is involved in recognizing patterns and faces and processing where we are in space [24]. It also contains Wernicke's area which functions in understanding written and spoken language. So damage here will result in deficits of these functions. Someone with damage here may not be able to recognize or process a person's facial features. They also may not be able to process what someone has said or written. 3. **Limbic system**: The limbic system contains the hypothalamus, hippocampus, and amygdala. Damage here results in inappropriate responses to the processing of information. In other words, damage can result in a disconnect from what a person sees and what a person does. This is because the Limbic system is the the communications network between the interpretation of objective and subjective information and the actual doing of or action you take based on that information.

//Brainstem//
The brainstem is the bridge between the brain and the spinal cord. It contains fiber tracts which connect the cerebrum to the spinal cord. It also is associated with 10 of the 12 pairs of cranial nerves. Damage here can be widespread and detrimental depending on where the damage is in the brainstem if it occurs.

//Cerebellum//
The cerebellum has three functional regions: the vestibulocerebellum, the spinocerebellum, and the cerebrocerebellum [24]. Symptoms of damage to the cerebellum include: asynergia, dysmetria, adiadochokinesia, intension tremors, and an ataxic gait [19].

1. The //Vesitublocerebellum// functions in the control of axial musculature in equilibrium control [24]. It's also active in coordinating head, eye, and body movements so damage here would result in an impairment of these functions. Symptoms would include ataxic and wide based gait with an excessive postural sway, and nystagmus [19].

2. The //Spinocerebellum// functions in the ongoing regulation of movement [24]. It corrects for deviations from the intended movement by comparing input feedback from the spinal cord with the intended movement command. It also functions to modulate muscle tone. Thus deficits from damage to this area would result in hypotonia and a loss of coordination of motor movement [19].

3. The //Cerebrocerebellum// functions in higher level functions including motor and non-motor skills [24]. It's involved in the preparation of an intended movement and it has a role in planning and timing voluntary movements. It is also involved in learned and skillful movements. One with damage to the cerebrocerebellum may not be able to perform the wanted movement even if they know what if feels like or looks like [19].

**//Prefrontal Cortex//**
The Prefrontal cortex is located in the anterior portion of the brain anterior to the frontal eye fields. The prefrontal cortex is involved in inhibiting inappropriate behaviors, decision making, and planning [20]. Damage to the prefrontal cortex leads to symptoms such as: an inability to plan or behave in a socially acceptable way. For example, someone may not be able to stop eating food when they're hungry so they may even take food off of someone else plate. Damage to this area can also result in the affected individual lacking empathy for others [20].

**//The Ascending and Descending Pathways//**


The ascending and descending pathways carry all the information we receive subjectively (from our own body) and objectively (all the information our body takes in from the environment) [21]. These pathways line the spinal cord and carry information to and from the cerebrum, cerebellum, and the various nuclei interspersed throughout the brain [24]. //__**Ascending Pathways**:__// The ascending pathways are made up of three primary tracts: the Dorsal Column Medial Leminiscal Tract (DCML), the Anterolateral Tract, and the Spinocerebellar Tract. The ascending pathways are primarily responsible for carrying information from the body to the brain to be processed. Damage to these pathways influences the information coming from below and at the site of the lesion.

1. **The Dorsal Column Medial Leminiscal Tract (DCML)**: The DCML conveys information to the higher brain centers and the primary somatosensory cortex from muscle and joint receptors and from touch and pressure receptors related to discriminative touch conveyed from the skin [21]. Depending on the level of the lesion, conscious perception of proprioception and fine touch may be lost partially or fully [21]. If the lesion occurs within the spinal cord the loss of sense will occur ipsilaterally whereas if it occurs after decussation in the medulla then loss of sensation will occur contra-laterally.

2. **The Anterolateral Tracts:** The Anterolateral tracts conveys information related to pain, temperature, and light touch to the thalamus via a-delta and C-fibers [24]. Lesions occurring at the spinal level below the point of decussation will cause a loss of pain and temperature sensations ipsilaterally [21]. However, the anterolateral tracts decussate immediately after entering the dorsal horn of the spinal cord so most sensational loss occurs contra-laterally of the effected side.

3. **The Spinocerebellar Tract**: The Spinocerebellar tracts convey information related to proprioception, balance, gait, stance information, and vibrations and discriminative touch. These tracts play a large roll in the coordination of movement [21]. In contrast to the anterolateral tracts and DCML, the spinocerebrellar tracts terminate in the cerebellum. Lesions to the spinocerebellar tracts result in ipsilateral loss of sensation at the site of lesion. Deficits will occur in gait and there will be a loss of knowledge of a body part in space [21]. However, this all depends on the size of the lesion and the area affected within the spinal cord.

__//**Descending Pathways**://__ The descending pathways are made up five primary tracts: the Corticospinal tract, the Rubrospinal tract, the Reticulospinal tract, the Tectospinal tract, and the Vestibulospinal tract.

1. **The Corticospinal Tract** (lateral and ventral) originates in the cerebral cortex and has two components that compromise it: the ventral and lateral corticospinal tracts. The ventral corticospinal tract carries information pertaining to balance and control of posture [24]. It also carries information concerned with performing synergistic whole-limb movements and is involved in coordination of movement of the head and body [22]. The lateral corticospinal tract helps with the control of fine movement of the distal extremities like the elbows and hands. Symptoms of corticopsinal tract lesions include: a positive babinski sign, muscle spasticity, absence of superficial abdominal reflexes, and loss of fine skilled movements depending on where the lesion site occurs [22].

2. **The Rubrospinal Tract** originates in the Midbrain and helps with the control of fine movements of the distal extremities [24]. It also is involved in muscle tone of flexor muscle groups especially in the upper extremity musculature. Rubrospinal lesions result in a temporary slowness of movement [23].

[[image:descendingpathwayspic.png width="517" height="414" align="right" caption="Figure 12: The Descending Pathways "]]
3. **The Reticulospinal Tract** originates in the Pons and is regulates the sensitivity of flexor responses to ensure that only noxious stimuli elicit the responses [24]. Damage to the reticulospinal tact cants cause harmless stimuli, such as gentle touches, to elicit a flexor reflex [23].

4. **The Tectospinal Tract** originates in the Midbrain and functions in balance and control of posture [24]. It too, is involved in synergistic whole-limb movements and coordination of movement of the axial musculature and head. It also helps in coordinating head and neck reactions to visual stimuli. Tectospinal lesions may result in dyskinesias or involuntary movements [23].

5. **The Vestibulospinal Tract** originates in the Pons is involved in in balance and control of posture. It is made up of the lateral and medial vestibulospinal tracts. It uses the information from the Vestibular system, visual system, and cerebellum to produce proper movement. The lateral vestibulospinal tract activates extensor limb muscles that support posture and resistance to falling while the medial vestibulospinal tract causes contraction of the neck muscles that tend to keep the head stable by opposing head movements ([|Vestibulocolic reflex]) [23]. Vestibulospinal lesions result in gait ataxia and postural instability [23].

//Pathophysiology //
MS has been incorrectly named as an autoimmune disease when in reality it is an immune-mediated disease. It is an immune mediated disease because we do not know the exact antigen that the immune system attacks or becomes sensitized to. If we knew what the antigen was then we could classify it as an autoimmune disease.

The exact cause of MS is unknown but what does occur is that the immune system goes rogue. This starts with T cells, which are a type of lymphocyte within the immune system, becoming sensitized to an unknown CNS protein which produces and signals for an infiltration of inflammatory cells. These inflammatory cells enter the central nervous system via the circulatory system and this results in damaging inflammation, myelin degradation, oligodendrocyte destruction, and axon degradation as well. The T cells are able to enter the central nervous system via the Blood Brain Barrier (BBB) by having the proper ligand or surface molecule that adheres to the proper receptor on the BBB. Once inside the CNS, the T cell is activated or triggered by an unknown neural protein and starts to attack the neural structures. Once activated, the T cell also influences the media type="youtube" key="yzH8ul5PSZ8" width="303" height="202" align="right" BBB to express more receptors to for the entry of more immune cells. The T cells also releases cytokines (i.e. Interleukin-1, Interleukin-6, TNF, INF) which dilate blood vessels and allows for the passage of even more immune cells such as B cells and macrophages to flood the CNS [12]. Once inside, the B cells release antibodies that tags the myelin sheaths, created by the oligodendrocytes, and the macrophages engulf and destroy the oligodendrocytes. This also results in the destruction of the myelin surrounding the axons of the neurons leaving behind plaque or sclera. When the myelin is attacked and destroyed the myelin sheaths form scar tissue (sclerosis) and thus hardens. This hardening of the myelin sheath and damaging of nerve fibers results in inadequate impulse transmission of signals.The destruction of these various neural structures not only results in scar tissue and inadequate impulse transmission, but it also results in reactive Astrogliosis. [|Reactive astrogliosis] is an increase in the activity of astrocytes in the presence of central nervous system damage or compromise [15]. These astrocytes serve a homeostatic function within the central nervous system and to the neural structures within it [15]. The damage within the CNS can impair neural, cognitive, andmechanical functions within the body and resultsin a wide range of dysfunctions depending on the area affected. Attacks on the CNS occur in bouts and this is due to regulatory T cells inhibiting the rest of the immune cells and thus reduces inflammation within the CNS. The video above gives a good presentation and representation of the Pathophysiology of MS [17].

//Signs and symptoms //
Because MS is sporadic in nature relative to where attacks can occur within the CNS, signs and symptoms can vary widely. Cognitive, neural, and mechanical or motor dysfunctions can result from MS attacks. MS is a very unique condition as no two people's symptoms are identical but some symptoms of MS are more common than others. Fatigue is found in 80% of MS cases and is the most prominent complaint among patients. Cognitive difficulties is the third most (50%) prominent complaint among patients behind pain (55%). Those with cognitive difficulties may struggle with processing information, learning and remembering new information, organizing, problem solving, and focusing. Other signs and symptoms include gait difficulties, spasticity, numbness, visual problems (optic neuritis), and vertigo or dizziness.

**//Risk factors //**
It's been reported that everyone has at least a 0.1% chance of developing MS. Your chance of developing MS can depend on three factors: where you live, the state of your health, and your genetic makeup. It also depends on other factors such as lifestyle and diet but the three listed above are the main factors we'll be covering.


 * Environmental factors**

Various environmental factors have been proven to play a role in the risk of developing MS. It's been shown that where you live even plays a role in risk of developing MS. This is based on how far an individual lives from the [|equator] [18]. In the northern United States (Separated by the 37th parallel) there's about 110-140 cases of MS per 100,000 people whereas in the southern United States there's about 57-78 cases per 100,000 people. If you go to countries closer to the equator such as Ecuador or Argentina you'll see reports of 18 cases of MS per 100,000 or even only 1.5 cases per 100,000 which was reported by Bolivia. But countries like Canada, Sweden, and Denmark, which are far away from equator reported 291 cases per 100,000 (Canada), 189 per 100,000 (Sweden), and 227 per 100,000 (Denmark) [2]. Studies have shown this may be due to Vitamin D deficiency which influences every cell in our body, providing nutrients for them [2]. It was reported that out of a survey of those with MS, 48% of the population were vitamin D deficient and only 14% of the population were above normal levels which is about 40 ng/mL [11].


 * Infectious, disease, and viral factors**

Various immune compromising factors can influence ones' chance of developing MS. People with type 1 diabetes, thyroid disease, or inflammatory bowel disease are at increased risk of developing MS [1]. Those who are vitamin D deficient are also at risk [11]. Those with Epstein-Barr syndrome, herpes, or Varicella-Zoster are at increased risk of developing MS [1]. Various bacteria, microbes, or viruses can all lead to demyelination or inflammation of myelin, so it's possible that any immune system compromising pathogen or health deficit can trigger the development of MS [6].


 * Genetic and Gender Factors**

Studies show your family, gender, age, and race all play a role in your risk of developing MS. However, MS is not classified as a hereditary disease. Those who are of Northern European or Canadian descent have been shown to have the highest risk of developing MS while those of Native American, African, or Asian descent have the lowest chance of developing MS [1]. If an individual's family member has MS that individuals risk of developing MS raises by about 1-3% [1]. If said individual has an identical twin, this raises the risk of developing MS by 30% [11]. Studies have also shown that 15% of individuals with MS have one or more family members or relatives with MS as well. MS can affect anyone at any age but is most commonly seen to develop anywhere in the age range of 20-50 years old.

Gender is a big factor in the development of MS. Studies show that women are twice as likely as men to develop MS [1]. This may be due to a blood brain barrier protein also known as S1PR2. S1PR2 controls the permeability of the blood brain barrier and is more prevalent in women and those with MS [5]. This is because women and those with MS produce much more amount of this protein [5]. Essentially, S1PR2 causes junctional proteins to unzip, allowing immune cells to pass through. Once across the blood brain barrier, the immune cells are free to damage the myelin coating the nerves in the brain and spinal cord. It's also been shown that sex hormones and history of pregnancy can even affect a women's chance of developing MS [7].

//Diagnosis //
The diagnosis of MS is a multistep and complicated process that requires multiple tests. It's difficult to test because there are no symptoms, physical findings, or laboratory tests that, on their own, can determine if someone has MS. It takes many tests being used together to rule out or make a positive diagnosis of MS. The diagnosis of MS requires blood tests, MRI, Cerebrospinal fluid testing, and evoked potential testing [8]. To positively diagnose MS a physician must find evidence of damage in at least 2 areas of the CNS and see MRI and spinal fluid changes, find evidence that each separate damaged site was created at least 1 month apart from the last, and finally, the physician must be able to rule out all other possible diagnoses.

Because diagnosis of MS uses many tests there is usually no reason to doubt an individual has MS after testing is concluded [8]. However, doubt can arise from rogue [|erythrocyte sedimentation rates] (ESR), an atypical MRI scan, or an unexpected sign or symptom such as fever, rash, headaches, or fits [8].


 * Blood test**: Blood tests can rule out other conditions that cause symptoms similar to those of MS, including Lyme disease, a group of diseases known as collagen-vascular diseases, certain rare hereditary disorders, and AIDS.


 * MRI**: MRI can be utilized for imaging the brain and spinal cord to determine where lesions sites are if they are present [12].


 * Cerebrospinal fluid testing** (CSF): A positive CSF test will show elevated levels of IgG antibodies as well as a specific group of proteins called oligoclonal bands and occasionally there are proteins that are the products of the breakdown of myelin. However, a positive CSF test cannot rule out or determine a diagnosis of MS as CSF abnormalities present themselves in other autoimmune/immune-mediated diseases. Studies have show that 10-15% of people with MS do not show CSF irregularities.


 * Evoked potential testing (EP)**: EP tests measure the electrical activity of the brain in response to stimulation of specific sensory nerve pathways. They are able to detect the slowing of electrical conduction caused by damage (demyelination) along these pathways even when the change is too subtle to be noticed by the person or to show up on neurologic examination. Because the diagnosis of MS requires evidence of demyelination in two distinct areas of the central nervous system, EP testing can help confirm the diagnosis by enabling the physician to identify a second demyelinating event that caused no clinical symptoms or was not otherwise apparent.

There are various syndromes, disease, and disorders that can be mistaken for MS. Such disease include: optic neuritis, devic disease (also known as neuromyelitis optica), Transverse myelitis, Foix-Alajouanine Syndrome (AV malformation), Acute disseminated encephalomyelitis, Marburg disease, Schilder's diffuse sclerosis, Balt's concentric sclerosis, and lyme disease [8]. Usually, genetic and MRI testing can diagnose these and help a physician tell them apart from MS.

//Multiple Sclerosis phenotypes //
There are four types of MS described by the United States [|National Multiple Sclerosis Society] and the [|Multiple Sclerosis International Federation]: Relapsing-Remitting MS, Primary-Progressive MS, Secondary-Progressive MS, and Clinically Isolated Syndrome [1].

1. //Relapsing-Remitting Multiple Sclerosis// (RRMS): RRMS is the most common disease course or type of MS. Initially, about 85% of people with MS are diagnosed with RRMS [6]. It is characterized by attacks which create new or increasing neurological symptoms and then are followed by periods of partial or complete recovery. It is also defined by inflammatory attack on the myelin as well as the nerve fibers themselves. RRMS is different from the other 3 types because: people with RRMS are more likely to have brain lesions, there are 3 times as many women effected with RRMS whereas the ratio of men to women is about the same, and RRMS has been found to be diagnosed earlier in life in the age range of 20 to 30 years old whereas PPMS's age range is 40 to 50 years old. The most common symptom of RRMS includes epsodic bouts of fatigue, visual problems, spasticity or stiffness, and cognitive problems. This type has 4 stages: Active, Not Active, Worsening, and Not Worsening.This type also affects women more often than men.

2. //Primary-Progressive Multiple Sclerosis// (PPMS): PPMS is characterized by worsening neurologic function (increase of disability) from the onset of symptoms, without early relapses or remission. About 15% of people diagnosed with MS are diagnosed with PPMS and men and women are effected almost equally in this disease course. With PPMS, individuals tend to This type also has 4 different stages: active, not active, with progression, and without progression.

3. //Secondary-Progressive Multiple Sclerosis// (SPMS): SPMS follows the same disease course as RRMS but eventually will transfer to a SPMS course in which there is a progressive worsening of function over time. It has the same stages as PPMS except the only difference is whether or not SPMS was preceded by RRMS.

4. //Clinically Isolated Syndrome// (CIS): CIS (not pictured above) is the least common form of MS. It's characterized by a first episode which must last 24 hours which presents the same qualities (inflammation and demyelination) as MS [10]. However, CIS does not meet the full criteria to be full-blown MS. Someone who is affected by CIS has a 20-80% chance of developing MS. The individual has a 20% chance of developing MS if it is accompanied by MRI evidence of no lesions and they have a 60-80% chance if it is accompanied by MRI evidence of positive lesions sites.

It should be said that Progressive-Relapsing Multiple Sclerosis(PRMS) has been included into the Primary-Progressive phenotype by the National Multiple Sclerosis Society.

Medications


When someone has an MS attack two main treatments are used: Corticosteroids and a Plasma exchange or Plasmapheresis [10]. Corticosteroids help reduce nerve inflammation so healing can occur. Plasmapheresis is a process where your blood plasma is removed from the circulatory system and then mixed with an albumin solution. After the mixing they then put the plasma back into your body. There are about 13 medications to help improve the quality of life for those with MS as well.7 are via injection, 3 are oral, and 3 are infused. Beta interferons are most commonly prescribed and they reduce the frequency of relapses. Glatiramer Acetate (Copaxone) can also be prescribed to help block or interfere with the immune systems attack on myelin. Other medications such as Dimethyl Fumarate or FIngolimod can be prescribed to help reduce relapse rate as well. Baclofen and tizanidine has also been prescribed to help reduce those with muscle spasticity. Lemtrada is given via IV infusion and is the only medication approved for patients who have taken two other therapies that have been ineffective

Lifestyle
Your lifestyle can impact your lifespan and your chances of developing MS. Your chances of developing MS are affected by lifestyle choices such as exercise and diet. Exercise has shown to improve overall health of someone diagnosed with MS as well as help counter MS symptoms such as fatigue, bladder and bowel dysfunction, mobility deficits and mood deficits [24]. Diet is important in overall health. While no diet has been proven to cure or alter the course of MS, maintaining a healthy diet (especially one in high in fiber and low in fat) can improve overall quality of life. Those who have MS must manage their stress level and find specific avenues to direct their energy towards as well in order to improve their overall quality of life.

Rehabilitation
Various forms of rehab are also used to help improve ones' quality of life who has MS. The overall goal of rehab is to just maintain and improve function. Physical therapy can help maintain motor functioning and prevent unnecessary complications such as muscle weakness, lack of mobility, atrophy, and other spasticity related conditions. Occupational therapy can be utilized to help enhance ones' independence, productivity, and safety in daily life activities. Cognitive rehab is used to evaluate and improve a person's ability to think, reason, concentrate or remember various activities and information [24]. Finally, vocational rehab is used to improve a person's ability to function in a work environment or regain necessary function to return to the work force. These all contribute and help those affected by MS improve their quality of life.

//Life expectancy //
Though MS is a life-long disease with no cure once diagnosed, MS does not significantly impact or alter the life expectancy of its' victims. New research has shown that those with MS generally live about 7 years less than the rest of the population due to disease complications.

//Conclusion //
Multiple Sclerosis affects approximately 10,000 new people each year and about 2.5 million people live with this immune-mediated disease today. MS is unpredictable in nature and the exact cause of MS is still unknown. We have made much progress in figuring out how to positively impact the quality of life for individuals who have MS but there is still much more to uncover about this sporadic disease and there is still much progress to be made in the medical field concerning treatment for this disease.

Ocrelizumab
A new drug in development, Ocrelizumab, has shown to significantly reduce new attacks in patients with relapsing MS, as well as slow the progression of symptoms caused by primary progressive MS (PPMS) [4]. Patients given Ocrelizumab presented with fewer brain lesions and brain volume loss [4]. Researchers also found that the risk of disability progression was reduced after 12 weeks and 24 weeks and the number of brain lesions during that time period was reduced [4]. However, more studies need to be done on Ocrelizumab to determine if it is safe long-term.

Gut Bacteria
Researchers are now saying bad gut bacteria or an insufficient amount of good bacteria may have a direct link to MS. They said that people who have MS have distinctly different gut biome versus a healthy individual. They found this through micro biome studies on control subjects and subjects with MS.

//Glossary of terms //

 * 1) **Immune-Mediated Disease** - Is a disease that lacks a definitive antigen or etiology triggered by a dysregulation of the immune system.
 * 2) **Autoimmune Disease** - A condition in which your immune system mistakenly attacks your body.
 * 3) **Oligodendrocyte** - A type of Central neural cell that functions in providing and supporting axons, and creating the myelin that encircles the axons.
 * 4) **Myelin** - A fatty white substance that surrounds the axons of some nerve cells which forms an insulating layer for faster conduction of electrical impulses
 * 5) **Central Nervous System** - The part of the nervous system consisting of the brain and spinal cord
 * 6) **T cells** - A type of white blood cell that plays a role in cell-mediated immunity.
 * 7) **Macrophage** - A large phagocytic cell which functions in eating pathogens usually at the site of an infection
 * 8) **B cells** - A lymphocyte created from bone cells that is responsible for producing antibodies
 * 9) **Meninges** - The three layers of protective tissue that surrounds the brain and spinal cord.
 * 10) **Cerebrospinal fluid** - A clear and colorless fluid that fills and surrounds the brain and spinal cord. It functions in providing a mechanical barrier against shock.
 * 11) **White Matter** - Type of tissue within the CNS which contains axons and neural cells surrounded by myelin.
 * 12) **Gray Matter** - A type of tissue within the CNS that contains neural cell bodies.
 * 13) **Motor Areas** - The functional areas within the brain concerned with the processing and action-phase of movement
 * 14) **Sensory Areas** - The functional areas within the brain concerned with processing sensory input and sending output of the processed information to the rest of the cortex.
 * 15) **Association Areas** - The region within the cortex that connects sensory and motor areas and is concerned with higher mental activities.
 * 16) **Cerebellum** - Also known as the "little brain". the cerebellum functions in balance and the coordinating and regulation of muscular activity
 * 17) **Brainstem** - Joins the brain and spinal cord and includes the midbrain, pons, and medulla oblongata.
 * 18) **Foramen Magnum** - The hole at the base of the skull through which the spinal cord passes
 * 19) **Ascending Spinal Tracts** - The spinal tracts that deliver information from the body to the brain.
 * 20) **Descending Spinal Tracts** - The spinal tracts that deliver cerebral output/commands to the rest of the body
 * 21) **Blood Brain Barrier** - A highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the CNS
 * 22) **Sclerosis** - An abnormal hardening of body tissue or scarring.
 * 23) **Ataxia** - A neurological deficit in which the affected individual has a lack of voluntary muscle coordination
 * 24) **Optic Neuritis** - Inflammation of the optic nerve which causes damage to the optic nerve itself.
 * 25) **Vertigo** - A sensation of whirling and loss of balance
 * 26) **Spasticity** - Is a muscular condition in which certain muscles are continuously contracted. This i usually due to damage within the brain or spinal cord.
 * 27) **Equator** - An imaginary line on the surface which is equidistant from the North and South poles splitting the Earth into Northern and Southern hemispheres.

**//List of relevant links or suggested readings (provide brief description)//**
//Paula and MS// media type="youtube" key="YWnnBHx_G3c" width="329" height="190"media type="youtube" key="Zxyl96aQnQA" width="308" height="190" These videos provide an in depth look at the life of Paula, who has MS, and how she has struggled and succeeded in her life with MS.

//Ocrelizumab// [|https://www.sciencedaily.com/releases/2017/01/1...113809.htm] This study shows the breakthrough of a new drug, Ocrelizumab, which reduces new attacks/symptoms and their progression in patients.

//Viruses and Multiple Sclerosis// https://www.ncbi.nlm.nih.gov/books/NBK2494/ This article gives a detailed look at how viral agents play a role in the chances of developing MS in an individual.

//Helper T Cells and// //Lymphocyte Activation// https://www.ncbi.nlm.nih.gov/books/NBK26827/ This article provides a detailed description about T cells and their function in adaptive immunity.

//The role of MRI in the diagnosis of Multiple Sclerosis// https://www.ncbi.nlm.nih.gov/books/NBK26827/ This article discusses the role MRI has in diagnosing MS

//Quiz //

 * 1) Which Immune system cell initially starts the process of myelin degradation in MS?
 * 2) B cells
 * 3) T cells
 * 4) Macrophages
 * 5) Eosinophils
 * 6) What is the most common reported symptom of MS?
 * 7) Fatigue
 * 8) Pain
 * 9) Muscle Spasticity
 * 10) Cognitive difficulties
 * 11) What is the most commonly reported phenotype of MS?
 * 12) PPMS
 * 13) SPMS
 * 14) RRMS
 * 15) CIS
 * 16) Which spinal tract is responsible for delivering the proprioceptive and fine touch information to the brain?
 * 17) Spinocerebellar tract
 * 18) Reticulospinal tract
 * 19) DCML
 * 20) Corticospinal tract
 * 21) Which test measures the electrical activity of the brain in response to stimulation of specific sensory nerve pathways?
 * 22) MRI
 * 23) CAT scan
 * 24) Evoked Potential Test
 * 25) Blood test
 * 26) Which protein is found more often in women and contributes to MS being twice as likely in women than men?
 * 27) S5RD2
 * 28) GB45F
 * 29) CB1JG
 * 30) S1PR2
 * 31) Who is the most likely to develop MS?
 * 32) A 30 year old man with diabetes
 * 33) A 35 year old woman without diabetes
 * 34) A 25 year old man without diabetes
 * 35) A 40 year old woman with diabetes

True or False

 * 1) MS is a fatal disease
 * 2) MS affects men more than women
 * 3) MS is linked to optic neuritis
 * 4) A T cell stops and starts the process of attacking the central nervous system
 * 5) It's been found that the farther you live from the equator, the less chance you have of developing MS.
 * 6) MS is very easy to diagnose and does not need multiple tests to diagnose
 * 7) Those affected with MS usually don't present with fatigue or pain
 * 8) Those affected with MS have a drastically shortened life span compared to those not affected with MS.

Short Answer

 * 1) Please give three different types of therapy an individual affected with MS can utilize to improve their quality of life and give a definition of what each therapy type does.
 * 2) Please explain why MS is sporadic in nature and what factors (very general) contribute to the development of MS.
 * 3) Please define "sclerosis"

Essay
Please describe the process or pathophysiology by which the immune system attack the central nervous system in MS, be specific

//References //
[1] “Multiple Sclerosis.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 4 Aug. 2017, www.mayoclinic.org/diseases-conditions/multiple-sclerosis/home/ovc-20131882. [] [2] “A Visual Look at New Worldwide Multiple Sclerosis Data .” Vitamin-D-Council, www.bing.comfwww.vitamindcouncil.org%2fa-visual-look-at-new-worldwide-multiple-sclerosis-prevalence-data%2f&p=DevEx,5065.1. [] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> [3] <span class="citation_text">“National Multiple Sclerosis Society: A Guide for Caregivers.” //AHRQ Innovations Exchange: Innovations and Tools to Improve Quality and Reduce Disparities//, innovations.ahrq.gov/qualitytools/national-multiple-sclerosis-society-guide-caregivers. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[4] ScienceDaily, ScienceDaily, www.sciencedaily.com/releases/2017/01/170109113809.htm. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[5] “Study Explains Why MS Is More Common in Women than in Men.” Healthline, Healthline Media, www.healthline.com/health-news/why-do-more-women-than-men-get-ms-051414. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[6] Donati, Donatella. “Viruses and Multiple Sclerosis.” Polymicrobial Diseases., U.S. National Library of Medicine, 1 Jan. 1970, www.ncbi.nlm.nih.gov/books/NBK2494/. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[7] “Women and Autoimmune Disorders.” EverydayHealth.com, 20 Dec. 2012, www.everydayhealth.com/autoimmune-disorders/understanding/women-and-autoimmune-diseases.aspx. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[8] Scolding, Neil. “The Differential Diagnosis of Multiple Sclerosis .” Jnnp.bmj.com. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[|http://][|jnnp.bmj.com/content/71/suppl_2/ii9.full] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[9] Rejdak, Konrad, et al. “Multiple Sclerosis: a Practical Overview for Clinicians | British Medical Bulletin | Oxford Academic.” OUP Academic, Oxford University Press, 4 July 2010, academic.oup.com/bmb/article/95/1/79/269828/Multiple-sclerosis-a-practical-overview-for. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[10] “Multiple Sclerosis.” Practice Essentials, Background, Pathophysiology, 27 Oct. 2017, emedicine.medscape.com/article/1146199-overview#a1. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[|http://emedicine.medscape.com/article/1146199-overview#a1] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[11] Mercola. “Vitamin D Is Better than ANY Vaccine.” Mercola.com, articles.mercola.com/sites/articles/archive/2012/01/04/why-this-vitamin-is-better-than-any-vaccine-and-improves-your-immune-system-by-35-times.aspx. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[12] Alberts, Bruce. “Helper T Cells and Lymphocyte Activation.” Molecular Biology of the Cell. 4th Edition., U.S. National Library of Medicine, 1 Jan. 1970, www.ncbi.nlm.nih.gov/books/NBK26827/. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[13] Traboulsee, A L, and D K Li. “The Role of MRI in the Diagnosis of Multiple Sclerosis.” Advances in Neurology., U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/pubmed/16400831. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[|://][|www.ncbi.nlm.nih.gov/pubmed/16400831] <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[14] “Women and Autoimmune Disorders.” EverydayHealth.com, 20 Dec. 2012, www.everydayhealth.com/autoimmune-disorders/understanding/women-and-autoimmune-diseases.aspx. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">[|http://][|www.everydayhealth.com/autoimmune-disorders/understanding/women-and-autoimmune-diseases.aspx] [15] “Astrogliosis.” Wikipedia, Wikimedia Foundation, 16 Oct. 2017, en.wikipedia.org/wiki/Astrogliosis. [|://en.wikipedia.org/wiki/Astrogliosis] [16] https://upload.wikimedia.org/wikipedia/commons/f/f1/Multiple_sclerosis.webm [17] https://www.youtube.com/watch?v=QpUMT-SA75Q video [18] Rosenberg, Matt. “Can You Name the 13 Countries That Lie on the Earth's Equator?” ThoughtCo, www.thoughtco.com/countries-that-lie-on-the-equator-1435319. https://www.thoughtco.com/countries-that-lie-on-the-equator-1435319 [19] “Cerebellum.” Centre for Neuro Skills Brain Injury Rehabilitation Programs, www.neuroskills.com/brain-injury/cerebellum.php. https://www.neuroskills.com/brain-injury/cerebellum.php [20] “What Is the Difference between the Prefrontal Cortex and Frontal Lobe? | Socratic.” Socratic.org, socratic.org/questions/what-is-the-difference-between-the-prefrontal-cortex-and-frontal-lobe. https://socratic.org/questions/what-is-the-difference-between-the-prefrontal-cortex-and-frontal-lobe [21] “The Ascending Tracts.” TeachMeAnatomy, 21 Oct. 2017, teachmeanatomy.info/neuro/pathways/ascending-tracts-sensory/. http://teachmeanatomy.info/neuro/pathways/ascending-tracts-sensory/ [22] https://www.slideshare.net/khadija7iqbal2/descending-pathways-drkhadija-1 [23] Spinal Reflexes and Descending Motor Pathways (Section 3, Chapter 2) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston, nba.uth.tmc.edu/neuroscience/s3/chapter02.html. http://nba.uth.tmc.edu/neuroscience/s3/chapter02.html [24] Class Notes

//<span style="font-family: 'Palatino Linotype','Book Antiqua',Palatino,serif;">Image References //
[1] Figure 1: https://upload.wikimedia.org/wikipedia/commons/b/b2/1205_Somatic_Autonomic_Enteric_StructuresN.jpg Figures [2][3][4[6][7][8][10][12]: Pearson anatomy text book [5] Figure 5: https://qbi.uq.edu.au/files/24323/Axon-neuron-brain-QBI.jpg [9] Figure 9: https://image.slidesharecdn.com/anatomyofcerebellum-100611084355-phpapp01/95/anatomy-of-cerebellum-25-728.jpg?cb=1276245947 [11] Figure 11: https://i.pinimg.com/originals/ea/e4/89/eae48913dfda59804de32ea403bed549.jpg [13]: Figure 13: http://www.assignmentpoint.com/wp-content/uploads/2017/01/Multiple-sclerosis-2.jpg [14] Figure 14: http://pt851.wdfiles.com/local--files/multiple-sclerosis-cell-bio/prevelancemap.JPG [15] Figure 15: https://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/media/medical/hw/h9991221.jpg [16] Figure 16: http://www.msunites.com/wp-content/uploads/Types-Of-MS-e1438507329372.jpg [17] Figure 17: https://www.researchgate.net/profile/Michael_Koss5/publication/26692726/figure/fig1/AS:338571857809409@1457733229972/Fig-1-Schematic-drawing-of-Rheopheresis-double-filtration-plasmapheresis.png [18]: Figure 18: https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2015/04/09/12/14/neuro-ms-physical-therapy-8col.ashx

Answers to Quiz Questions: Multiple Choice: T/F:
 * B
 * A
 * C
 * C
 * C
 * D
 * D
 * F
 * F
 * T
 * T
 * F
 * F
 * F
 * F

Short Answer: Essay:
 * 1) Physical Therapy, Occupational Therapy, and Cognitive rehab. Physical therapy can help motor functioning and Occupational Therapy helps an individual being able to complete daily life tasks. Cognitive rehab helps an individual with problem solving and thinking.
 * 2) MS is sporadic in nature because the exact cause of it is unknown. It can be triggered by multiple factors including: environmental factors, infectious/disease factors, and genetic factors.This makes it unpredictable as to when it will develop and how it will develop.
 * 3) Sclerosis means an abnormal hardening of body tissue or scarring.
 * 1) The attack starts with T cells, which are a type of lymphocyte within the immune system, becoming sensitized to an unknown CNS protein which produces and signals for an infiltration of inflammatory cells. These inflammatory cells enter the central nervous system via the circulatory system and this results in damaging inflammation, myelin degradation, oligodendrocyte destruction, and axon degradation as well. The T cells are able to enter the central nervous system via the Blood Brain Barrier (BBB) by having the proper ligand or surface molecule that adheres to the proper receptor on the BBB. Once inside the CNS, the T cell is activated or triggered by an unknown neural protein and starts to attack the neural structures. Once activated, the T cell also influences the BBB to express more receptors to for the entry of more immune cells. The T cells also releases cytokines (i.e. Interleukin-1, Interleukin-6, TNF, INF) which dilate blood vessels and allows for the passage of even more immune cells such as B cells and macrophages to flood the CNS. Once inside, the B cells release antibodies that tags the myelin sheaths, created by the oligodendrocytes, and the macrophages engulf and destroy the oligodendrocytes. This also results in the destruction of the myelin surrounding the axons of the neurons leaving behind plaque or sclera. When the myelin is attacked and destroyed the myelin sheaths form scar tissue (sclerosis) and thus hardens. This hardening of the myelin sheath and damaging of nerve fibers results in inadequate impulse transmission of signals.The destruction of these various neural structures not only results in scar tissue and inadequate impulse transmission, but it also results in reactive Astrogliosis.