Multiple Sclerosis
Introduction:
Multiple Sclerosis (MS) is a chronic disorder in which the individual’s immune system attacks itself. This autoimmune disorder damages the myelin sheath that covers and facilitates conduction through the axon of the nerve cells (neurons). This effects both the brain and the spinal cord, resulting in difficulty achieving movements, sensations, and even basic functions. [6][7]
Functional Anatomy:
Neurons are nerve cells that together make up the nervous system. Neurons are responsible for the ability to mentally function including: memory, sense, emotion, thought, movement and more. Although they are located in the brain and spinal cord, their axons reach all over the body. Some are short while others span long distances reaching the limbs. A neuron is composed of:
o Soma: the cell body
o Axon: projection that conduction electrical signal
o Dendrite: branches that allow for communication
Neurons are send and receive electrical signals through action potentials that allow for communication between other neurons. Ultimately these signals reach the necessary organs and results in an action desired by the person. “Myelin is the fatty substance that coats and protects nerve fibers in the brain and spinal cord.” It can be compared to an insulation coat, where electrical conduction propagate faster and with more ease. When this insulation is damaged and the axon is exposed, the electrical conduction or message, is then either blocked or slowed down. Such difficulty in relaying messages can cause disruption/ difficulty in the tasks that an individual might want to perform. [2]



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The dendrite receive neurotransmitters (chemicals) that either meet the threshold requirement or not. If there is an adequate amount of stimulus, the signal will travel through the soma until it gets to the axon hillock, or the initial segment of the axon. This is the trigger zone in which the action potential is generated. As the wave of depolarization travels though it begins to enter and propagate through the axon. The myelin that covers the axon facilitates the speed at which the electrical impulse is traveling and ensures its arrival to the next terminal. Such an action potential is possible because of the voltage gated ion channels. As the voltage reaches threshold, the sodium channels begin to open and the influx of sodium allow for depolarization. As the depolarization continues it will reach the threshold for an action potential. It is the action potential that allows the message to be sent through. As the action potential is reached the sodium channel is closed and the potassium one opens, repolarizing the cell. As it reaches the end of the axon it will then be able to communicate and stimulates the neighboring cell. [6][7]

Input/Output:
As previously mentioned axons are spread throughout the body. As legions are formed on the axon and signaling is deteriorated, actions that were previously fluid and done with ease are now difficult to achieve if at all possible. The central nervous system is composed of the brain and spinal cord, however is responsible for motor, sensory, sight and more. With such disruption MS patients may have difficulty with vision, walking, cognition and overall motor control.

Motor:

  • Corticospinal
    • Responsible for movement and overall control of the skeletal muscles
    • Begins in the precentral gyrus/ primary motor cortex which can either innervate a pathway that will control head and trunk or limbs. It will continue to travel down though the brain stem into the medulla where there are two options present, decussate through the pyramids for limb control, and continue down for head and trunk control. As the fibers leave the brain stem they will separate into either, lateral (limbs) or anterior (head and trunk) pathways. It is at the anterior tract the fibers ultimately decussate into the pyramids. The make there way into the horn. Last projecting into muscles that are bring recruited for the motion
  • Medial
    • Reticulospinal: regulation of reflex
    • Tectospinal: regulation of eye, head, neck and upper limb response to stimuliVestibulospinal: balance and muscle tone
  • Lateral:
    • Rubrospinal: upper limb tone and movement
  • Spinocerebellar
    • Cerebellar
    • Muscle tone and balance


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Sensory:
  • Spinothalamic
    • Anterolateral pathway
    • Nociceptor, mechanoreceptor, thermoreceptor, chemoreceptor
    • A delta III fibers (free nerve endings)-> dorsal ganglion(1st order neuron) -> dorsal root -> dorsal horn-> synapse on the Substantia Gelatinosa->it then exists and crosses over (decussate) through the midline and hooks/ attaches/synapses to the AST->ascends to the ventral posterior lateral nucleus of the thalamus (3rd order neuron)->Primary somatosensory cortex-> into layer 4 located in the post central gyrus

*Lateral is responsible for outer portions of the body


  • Dorsal Column- Medial Lemniscal (DCML):
    • Including Meissner’s, Merkel, Pacinian, Ruffini
    • Touch sensation and proprioception
    • 1a-> dorsal ganglion (1st order neuron) -> dorsal horn-> lumbar cord-> through the caudal (2nd order neuron) where it will either synapse on the Cuneate(T6 and above, upper extremities) or Gracile (T7 and below, lower extremities)->it then exists and crosses over (decussate) through the midline and hooks/ attaches/synapses to the medial meniscal-> ascends to the ventral posterior lateral nucleus of the thalamus (3rd order neuron)->Primary somatosensory cortex-> into layer 4 located in the post central gyrus
*Each area that it innervates or projects into is responsible for a body segment, and each layer is responsible for relaying different information.

Visual:
  • Cone/Rods-> Bipolar cells-> Ganglion axon leads to and forms the optic nerve ( where the myelin can be damaged and vision becomes impaired)-> optic chiasm-> optic tract-> LGN of the thalamus-> primary visual areas located in the occipital lobe.
*Lesion at the MLF (eye movement) would cause nystagmus
*Main cranial nerves affected include the 2nd and 3rd cranial nerve, with supplementary effects from 4th and 6th.

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Multiple Sclerosis Overview:
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MS is a progressive disease, slowly demolishing the central nervous system. Myelin is helpful in the conduction of action potentials (electrical signals). When this conductive layer is damaged communication is cut, resulting in poor interconnection between the CNS and the rest of the body. MS greatly effects an individual’s vision, balance, strength, sensation, coordination and bodily functions. Myelin is a component of the nervous system that is disrupted in multiple sclerosis, resulting in neuro-axonal degeneration. Nerve damage is caused by inflammation, causing an attack on the body’s own nerves. Myelin is made of up lipids(fatty substances) and proteins. In addition to protecting the axon, it also helps nerve signals travel quickly from one part of the body to another, or to the brain. When destruction occurs signals that are sent travel more slowly and less efficiently. MS attacks myelin, breaking it down and interrupting nerve signals. Because of the damagedmyelin, scar tissue is formed, increasing the difficulty in communication. The common age where symptoms become evident is between 20 and 40 years old. However some can present symptoms as early as 15 and as late as 60 years old. Women are twice as likely to develop MS compared to men. Descendants of northern European ancestry are the population most affected. It is also more prevalent in North America and Europe, some suggest it is due to the lack of vitamin d, due to the reduced sun exposure in colder months [4]



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Causes:

The exact explanation has yet to be discovered as to why the body’s own immune system is responsible. The immune cells (T-cells) attack the myelin, which serves to insulate and facilitate communication. The myelin functions to increase the speed of transmission of the nerves impulses. It is also responsible for preventing the interruption of one cells signal from another. The afflicted area is plagued with plaque, as the number of plaque filled areas increases the more progressive/ worse the symptoms become. However there is no set rate or predictable progression of MS, meaning and individuals experience is unpredictable.
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Some contributing factors that are thought to play a role in MS’s trigger include: environment, infection, genes and immunologic. Environmental factors: effects of migration. The risk one has is dependent on early environmental factors. This might cause a change in the individual’s immune response, increasing susceptibility. Viral infections that occurred earlier in life might be a factor that triggers the disorder, a slow and progressive transition. There is no clear answer at this point in time, only suggestions or hypothesis of what could potentially be the cause. There are two main theories:
  1. The immune system is attacking a virus, which results in the damage of the myelin as a consequence.
  2. There is a thought that the individual’s immune system mistakes the myelin for a viral protein. This could have been a protein that had previously infected the individual. This results in the autoimmune response. [6][7]

Symptoms:
MS effects each person differently, each person having a unique experience. There are multiple symptoms of which can be mixed and displaying different levels of severity. Those with multiple sclerosis are at risk for greater complications that can great difficult life including muscle stiffness, paralysis, mental changes, and more. [2] MS is divided into 4 types:
  • Relapsing remitting multiple sclerosis (RRMS): this is the most commonly occurring pattern. The individual has periods of attacks followed by a recovery stage where there is a complete or majority improvement. The period of time between attacks can occur annually or as the disorder progresses, within a couple of months of the last bout. (75 % of the MS population have this form of MS)
  • Primary progressive (PPMS): MS progresses with little to no periods of improvement.
  • Secondary Progression (SPMS): they begin with RRMS and progress into worsening symptoms.
Most people have a set of symptoms and its severity which stay consistent throughout their life. However some, like those with progressive relapsing multiple sclerosis continuously experience worsening symptoms. There is a range of symptoms because of the wide area where the plaque can form which will effect different areas/functions.

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List of symptoms:
  • Muscle weakness which results in difficulty walking
  • Imbalance/ lack of coordination
  • Numbness
  • Distorted visions (blurred or double )
  • Fatigue
  • Tremors
  • Paralysis
  • Pain : chronic, usually sharp commonly on facial, neck and throughout the back
  • Dizziness
  • Difficulty in completely simple everyday tasks
Double vision or eye tremor (nystagmus) indicates that the nerve pathways controlling the eyes muscles have been impacted. Involvement with the ocular nerve may result in blind spots.
Pain is associated with multiple sclerosis can come in two types primary pain and secondary pain. Primary pain comes in bursts, randomly afflicting the individual and is caused by the disease itself. Secondary pain is associated with side effects of other symptoms that have developed as a result of the disorder.

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Because the CNS is affected in the disorder, cognitive changes can occur. One’s memory, mood, personality are commonly affected. Such circumstances increases the rate of depression within the MS population. It can become severe enough to required treatment. For the majority of the population MS will not affect the patient’s life expectancy, rather the quality of life is affected. [3][6][7]Diagnosis:
As previously mentioned, there is yet to be a single clear answer as to what cases and what determines MS. There are a list of symptoms that can be used to diagnose the patients, but no test can actually confirm. A patient must undergo multiple tests and observation over time. Medical history and neurological exams are widely used. A patient with a detailed history will be able to more clearly indicate if the individual has MS. [6][7] The type of MS the patient has is important to track as well. As previously mentioned there is no clear origin of MS, but among the suggestions is a viral infection. Epstein-Barr virus (EBV) currently provides the strongest evidence for viral trigger of MS. Along with the viral infection theory studies suggest that an environmental factor that could potentially lead to the development, or evolvement of MS is the lack of vitamin D, sun exposure. Because vitamin D has an important immune function, the lack of it may result in a weakened system thus making one more susceptible to develop the disorder.




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A neurological exam will be performed by the physician when diagnosing. The physician will be check one’s reflexes, visions including light reactions, eye movement, balance and ability to walk with stability, and other tests to determine the competence of the nervous system.
Tests:

  • MRI of the brain can reveal plaque on the brain and spinal cord. With the addition of Gadolinium is able to indicate whether a plaque is older or new, which can help with determining when new symptoms emerge.
  • Based on the patient’s immune system protein level obtained from a spinal tap when elevated indicates MS.[6][7]
  • Visual pathway: optic neuritis is common among those who are diagnosed with Multiple Sclerosis. A test is performed to examine the electrical responses when there is a visual stimulus, Visual Evoked Potential. [3]
  • Limb Pathway: Somatosensory Evoked Potential is a test performed to indicate whether this is a disturbance in the pathways that innervate the limbs. An electrical stimulus is given and it will determine whether there is a disturbance with its conduction.[3]
  • An individual’s prognosis is dependent on their MS type and the amount of repeated relapse, progression, and severity of these. May MS patients will still be able to function independently after 25 years.[3]
Treatment:
There is no cure for multiple sclerosis as of today, however there are many therapies that can facilitate an individual’s life, reducing the numerous symptoms. Drugs aid in the slowing of the progression. With care drug therapy can help treat the symptoms and even avoid further complications associated with MS. Drugs are to be administered on a patient to patient basis, however no two cases are exactly the same. Along with drug therapy one should be involved in a rehabilitative therapy. Strengthening weakened muscles is key. The goal is to maintain the range in motion, and flexibility. Exercise is important to maintain the individual’s functional capacity. The patient should be able to adapt to his or her environment. [6][7]
Though attacks are unpredictable and there is yet no cure there are many steps one can take to prevent or minimize the onset of an attack. These include a well-balanced and nutrition diet, getting adequate rest, living an active lifestyle, and being tobacco free.

Summary:
Multiple sclerosis is a disorder that affects the brain and spinal cord, through the damaging of the myelin that covers the axon. The myelin is responsible for surrounding, protecting and assisting in the conduction of the axon. Damages result in a slower or impeded electrical signal communication. This results in muscle weakness, pain, vision troubles, and more. The exact cause has yet to be narrowed down but studies suggest that the autoimmune disorder is caused by environmental, genetic, immunological trends. Though there is no cure yet there are many options including drugs and therapy. With care, symptoms can be relieved and progression can be delayed.
Key terms:
Myelin: fatty tissue that insulates the axon, assists with conduction and relaying of massages.
Plaque: lesions or scar tissue that develop on the axon
Relapse: when the symptoms worsen for a period of time caused by inflammation.
Progression: when symptoms begin to accumulate, they never fully disappeared.
Soma: the cell body
Axon: projection that conduction electrical signal
Dendrite: branches that allow for communication
Axon hillock: initial action potential, trigger zone
Voltage gated: An appropriate voltage is required in order to generate movement
Threshold: specific voltage needed in order for message to be sent


Questions:

Multiple Choice:

1) Which vitamin deficiency is thought to trigger MS?
a. Vitamin A
b. Vitamin C
c. Vitamin D
d. It is actually a deficiency of a mineral, magnesium

2) An action potential initiates:
a. Axon Hillock
b. Soma
c. Dendrite
d. Axon Terminal

3) All of the following are symptoms of MS with the exception of:
a. Muscle weakness
b. Imbalance
c. Numbness
d. Neuromyelitis Optica

4) Pathway(s) that is/are effected by MS:
a. Spinal
b. Vestibular
c. Ocular
d. None of the above
e. All of the above

T/F:

1) Multiple Sclerosis is twice as likely to affect men.

2) Majority diagnosed with MS are expected to have a shortened lifespan and suffer debilitating regression.

3) MS is an autoimmune disorder that damages the myelin sheath of an axon.

4) Magnetic resonance imaging is the only definitive exam capable of diagnosing multiple sclerosis.

5) Those from a northern European descent are more likely to develop MS.

Short answer/Essay

1) Explain the steps of how a neuron sends an action potential

2) Explain the differences between the types of multiple sclerosis

3) For what reason(s) would multiple sclerosis present different symptoms doe each patient?

Answers

MC:

  1. 1. C 2.A 3.D 4.E

T/F:
1. F 2.F 3.T 4. F 5. T

Reading:

All of the references sited below give detailed information about this sidorder. However for a simple layout with dense yet concise content I recommend reading the information on the following site : https://msfocus.org/Get-Educated/Common-Questions#What is Multiple Sclerosis


References:
  1. Lerner, K. Lee, and Christine Miner Minderovic. "Neuron." The Gale Encyclopedia of Science, edited by K. Lee Lerner and Brenda Wilmoth Lerner, 5th ed., vol. 6, Gale, 2014, pp. 2996-2999. Gale Virtual Reference Library, proxy2.noblenet.org/login?url=http://go.galegroup.com/ps/i.do?p=GVRL&sw=w&u=mlin_n_gordon&v=2.1&it=r&id=GALE%7CCX3727801669&asid=1e11a5ee0d826f1f680921e9147b3c56. Accessed 30 Nov. 2016.
  2. Mayo Clinic Staff Print. "Multiple Sclerosis." Overview - Multiple Sclerosis - Mayo Clinic. N.p., 01 Oct. 2015. Web. 21 Nov. 2016.
  3. "Multiple Sclerosis Foundation - Common Questions." Multiple Sclerosis Foundation - Common Questions. MS Focus Staff, n.d. Web. 22 Nov. 2016.
  4. "Multiple Sclerosis: MedlinePlus Medical Encyclopedia." MedlinePlus Medical Encyclopedia. N.p., n.d. Web. 29 Nov. 2016.
  5. "What Is MS?" National Multiple Sclerosis Society. N.p., n.d. Web. 23 Nov. 2016.
  6. Slomski, Genevieve T., PhD, and Emily R. Larson, PhD. "Multiple Sclerosis." The Gale Encyclopedia of Genetic Disorders, edited by Tracie Moy and Laura Avery, 4th ed., vol. 2, Gale, 2016, pp. 1215-1220. Gale Virtual Reference Library, proxy2.noblenet.org/login?url=http://go.galegroup.com/ps/i.do?p=GVRL&sw=w&u=mlin_n_gordon&v=2.1&it=r&id=GALE%7CCX3630400350&asid=ae43b9cb6199db412130b06e1d80585e. Accessed 28 Nov. 2016.
  7. Slomski, Genevieve T., and Tish Davidson. "Multiple Sclerosis." The Gale Encyclopedia of Medicine, edited by Jacqueline L. Longe, 5th ed., vol. 5, Gale, 2015, pp. 3446-3452. Gale Virtual Reference Library,proxy2.noblenet.org/login?url=http://go.galegroup.com/ps/i.do?p=GVRL&sw=w&u=mlin_n_gordon&v=2.1&it=r&id=GALE%7CCX3623301234&asid=09262cdf0914d6e7126170b30822013c. Accessed 28 Nov. 2016.
*Class notes were also used