Multiple sclerosis adjusted to publish


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This is a comprehensive & updated presentation on Multiple sclerosis. It is intended for healthcare professionals and focuses on pathophysiology. It is very rich in details, diagrams (on every slide), and interactive content when in slide presentation mode. The presentation has also hyperlinks to videos (3 D Patho) and controversial treatments.
It concludes with a case study & follow up. If interested in detailed answers, please email:
Thanks, Ahmad

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  • In areas farther from the equator, MS is known to be more frequent leading some researchers to believe in a causative link with lack of vitamin D. There are notable “MS clusters” in certain areas where environmental and industrial toxin exposures seem to have occurred. Research is being conducted to explore links to virus exposure during childhood, although none have been proven a definite trigger thus far. Genetics appear to play a role as having a first-degree relative with MS increases one’s chances of developing MS. It is possible there is a genetic factor predisposing one to initiate an immune response to an environmental agent.
  • such as interactions with associated adaptor proteins like ZO-1, ZO-2 and ZO-3
  • *This results in disruption of the BBB, causing an increase in barrier permeability due to the degradation of tight junctions which maintain barrier integrity. Inducing the formation of tight junctions can restore BBB integrity and reduces its permeability, which can be used to reduce the damage caused by lymphocyte and monocyte migration across the barrier as restored integrity would restrict their movement.**Activation of macrophages and lymphocytes and their migration across the barrier may result in direct attacks on myelin sheaths within the central nervous system, leading to the characteristic demyelination event observed in MS. After demyelination has occurred, the degraded myelin sheath components, such as myelin basic proteins and Myelin oligodendrocyteglycoproteins, are then used as identifying factors to facilitate further immune activity upon myelin sheaths. Further activation of cytokines is also induced by macrophage and lymphocyte activity, promoting inflammatory activity as well continued activation of proteins such as matrix metalloproteinases, which have detrimental effect on BBB integrity
  • Early in the course of the disease, more oligodendrogliocytes are preserved in the plaque; thus some degree of remyelination remains possible. In other patients, there is a complete loss of oligodendrogliocytes. In this group of patients, possibility of remyelination is dramatically decreased. These observations may also imply that heterogeneous mechanisms are responsible for the disease induction in different patents.
  • A number of T-cell receptors and their recognition of antigens combined with Major Histocompatibility Complex Class II molecules (Trimolecular Complex) have been studied.
  • A number of T-cell receptors and their recognition of antigens combined with Major Histocompatibility Complex Class II molecules (Trimolecular Complex) have been studied.
  • There is a considerable interest in a theory that exposure to a virus may lead to immunopathologic condition resulting in MS.
  • There is a considerable interest in a theory that exposure to a virus may lead to immunopathologic condition resulting in MS.*A recent investigation suggests that HHV6 (Roseola virus) is associated with areas of demyelination in MS patients.
  • NAWM (Normal appearing White Matter) border with the lesion: These areas contained activated microglia, antibodies binding to astrocytes, axons, oligodendrocytes and dendritic cells along blood vessels. No T or B cells are present.Lesion external layer: Number of oligodendrocyte cell bodies decreases. Remaining oligodendrocytes are sometimes swollen or dying. Myelin sheaths are still intact but swollen. Small increase in microglia and T cells.Active layer:Phagocyticdemyelinating areas: There is myelin debris taken up by local microglia and phagocytes entering from the bloodstream. More T cells in these areas, and in the space adjacent to blood vessels.Recently demyelinated tissue: Tissues were full of myelin-containing phagocytes. Signs of early remyelination together with small numbers of oligodendrocytes. Large numbers of T cells, B cells, and other immune cells concentrated around blood vessels.Inactive layer: Again activated microglia and dendritic cells were also found around blood vessels.
  • The diagnosis of Multiple Sclerosis (MS) requires evidence of at least two different regions of the central white matter that have been affected at different times. It cannot be based on any single symptom or sign, but on a total clinical picture that indicates involvement of different parts of the central nervous system at different times. (Greenberg 2012, p 237).
  • *(oligoclonalIgG bands different from any in the serum or elevated IgG index)
  • Polyphenols and carotenoids, polyunsaturated fatty acids and DHA, have all been found to decrease the production of inflammatory molecules associated with MS. Limiting saturated fats of animal origin have been reported to induce “remission of the disease and produces beneficial effects in MS patients” (Swank & Goodwin, 2003, p. 161)
  • *MSIF is an international body linking the activities of national multiple sclerosis societies around the world. MSIF seeks to work in worldwide partnership with member societies and the international scientific community to eliminate multiple sclerosis and its consequences, and to speak out globally on behalf of those affected by multiple sclerosis. MSIF works to achieve this through the following key priorities: international research; development of new and existing societies; exchange of information; advocacy.
  • * provides timely, evidencebased information about emerging therapies for people affected by multiple sclerosis and healthcare professionals.The Collaborative’s goal is to promote optimal, personalized treatment by facilitating effective doctor-patient communication and collaborative decision-making.
  • Multiple sclerosis adjusted to publish

    1. 1. Presented by: Ahmad Amirdash, BBA, BSN, CCRN 1
    2. 2.  Anatomy and Physiology  Common Etiology  Pathophysiology  Prevalence & Morbidity  Clinical Manifestations  Diagnostics  Classification & Prognosis  Treatment (current and experimental)  Nutrition  Psychosocial issues and resources available  Case Study  References 2 Presentation Outline
    3. 3. Anatomy and Physiology  In the normal nerve fiber, the central core of the fiber (axon) conducts the action potential for cell movement.  This large fiber is surrounded by a myelin sheath, made up of lipoproteins. 3Hall & Guyton, 2011
    4. 4. Anatomy and Physiology The sheath insulates the fiber for better nerve cell transmission.  There are two types of myelin:  central nervous system myelin: coats the nerve fibers of the “white matter” in the brain and is produced by oligodendrocytes.  Peripheral nervous system myelin: coats the motor neuron fibers and is produced by Schwann cells. 4Hall & Guyton, 2011
    5. 5. Anatomy and Physiology 5
    6. 6. Anatomy and Physiology 6
    7. 7. Anatomy and Physiology  The myelin sheath is so thick that almost no ions can flow through it. They must be transmitted through nodes of Ranvier, which occur once every 1-3 mm along the sheath.  These nodes create “saltatory conduction” which allows the nerve impulse to jump along the fiber in succession, leading to transmission of the impulse. 7 (, n.d.)
    8. 8. Anatomy and Physiology  This “saltatory conduction” increases the velocity of myelinated fiber transmission as much as 5-50 fold. 8(Hall & Guyton, 2011) (, n.d.)
    9. 9. Anatomy and Physiology  Small unmyelinated nerve fibers have as little velocity as 0.25 m/sec while large mylinated fibers transmit at velocities reaching 100 m/sec which is approximately the length of a football field in one second. 9Hall & Guyton, 2011
    10. 10. Anatomy and Physiology with MS  In patients with multiple sclerosis, the myelin sheath is attacked by an immune response.  Specifically, CD4 T cells, macrophages and microglial cells initiate an attack on the sheath after passing through the blood-brain barrier 10(Rolak, 2003) (Riccio et al, 2010)
    11. 11. Anatomy and Physiology with MS  The attacks leave holes in the myelin, causing the axon to be exposed, decreasing conduction of the nerve impulses in the CNS and the PNS.  This leads to a slowing of conduction or complete failure of the impulse to reach its destination. 11(Rolak, 2003) (Riccio et al, 2010) (, n.d.)
    12. 12. 12
    13. 13. Anatomy and Physiology with MS  Demyelination can also lead to “cross-talk” of nerve fibers, allowing nerves to transmit signals inappropriately causing confusion of the impulse. 13(Rolak, 2003) (Riccio et al, 2010) (Mayo Clinic, nd)
    14. 14. Common Etiology  The exact cause of Multiple Sclerosis is unknown but it is widely believed it is an immune-mediated process.  In areas farther from the equator, MS is known to be more frequent. Lack of vitamin D  MS clusters: Environmental and industrial toxin exposures  Genetics: first-degree relative with MS  Smoking has also been shown to be an independent risk factor  Stress may be a risk factor although the evidence to support this is weak. 14("National Multiple Sclerosis Society," n.d.)
    15. 15. Pathophysiology Pathology and Distribution:  Pathological Hallmarks of Multiple Sclerosis are perivascular inflammation and demyelination evidenced on histological sections.  Disseminated white matter lesions or plaques which can occur anywhere within the white matter of the CNS.  The most frequently affected sites are the optic nerves, the brainstem, the cerebellum and the spinal cord. 15Lectures: Pathology (n.d.)
    16. 16. Pathophysiology  In the cerebral hemispheres periventricular distribution of plaques is often seen.  Plaques located nearby the gray matter may rarely spread into the gray matter, including deep nuclei and the cortex  There often is axon sparing within the plaque. 16Lectures: Pathology (n.d.)
    17. 17. Pathophysiology: Crossing the BBB Mechanisms of Plaque Evolution: • The blood-brain barrier (BBB) is disrupted at the onset of symptoms. • At the onset of symptoms, is not known yet whether demyelination precedes or is secondary to inflammation. 17Lectures: Pathology (n.d.)
    18. 18. 18Schematic sketch showing constitution of blood vessels inside the brain
    19. 19. 19 Part of a network of capillaries supplying brain cells A cortical microvessel stained for blood– brain barrier protein ZO-1
    20. 20. Pathophysiology Mechanisms of Plaque Evolution: • Lymphocytes contribute to pathologic processes by means of antibody- and cell-mediated immunity (direct mechanism) or by secretion of lymphokines and cytokines (indirect mechanism.) • The macrophages in those lesions contain myelin fragments or myelin breakdown products. 20Lectures: Pathology (n.d.)
    21. 21. 21 The astrocytes type 1 surrounding capillaries in the brain
    22. 22. Blood–brain barrier disruption  The BBB is composed of endothelial cells which line the blood vessel walls of the central nervous system.  Compared to normal endothelial cells, the cells lining the BBB are connected by occludin and claudin which form tight junctions in order to create a barrier to keep out larger molecules such as proteins.  In order to pass through, molecules must be taken in by transport proteins or an alteration in the BBB permeability must occur* 22 (Minagar & Alexander, 2003) (Correale, & Villa , 2007)
    23. 23. Blood–brain barrier disruption  BBB disruption is the moment in which penetration of the barrier by lymphocytes occur and has been considered one of the early problems in MS lesions.  The BBB is compromised due to active recruitment of lymphocytes and monocytes and their migration across the barrier.  Release of chemokines allow for the activation of adhesion molecules on the lymphocytes and monocytes, resulting in an interaction with the endothelial cells of the BBB which then activate the expression of matrix metalloproteinases to degrade the barrier 23(Correale, & Villa , 2007)
    24. 24. Blood–brain barrier disruption  Increase in barrier permeability due to the degradation of tight junctions which maintain barrier integrity. *  Activation of macrophages and lymphocytes causes direct attacks on myelin sheaths in the CNS  After demyelination, degraded myelin sheath components become identifying factors to facilitate further immune activity  Further activation of cytokines by macrophages and lymphocytes to mount further inflammatory activity.  Continued activation of proteins such as matrix metalloproteinases leads to more BBB disruption ** 24(Cristante et al, 2013) (Correale, & Villa , 2007)
    25. 25. 25
    26. 26. 26
    27. 27. Pathophysiology Ultrastructural Characteristics of plaques:  separation of the outer lamellae of the myelin sheath.  degenerative changes in myelin.  infiltration with macrophages or microglia with phagocytosis of myelin.  preservation of axons.  CNS lesions in MS are classified as early active, inactive, early remyelinating, and late remyelinating. 27Lectures: Pathology (n.d.)
    28. 28. Pathophysiology  The severity of demyelination may be assessed by relative preservation or destruction of oligodendrogliocytes.  Loss of myelin results in one or all of the following: • conduction block at the site of lesion • slower conduction time along the affected nerve • increased subjective feeling of fatigue secondary to compensation for neurologic deficits 28Lectures: Pathology (n.d.)
    29. 29. Pathophysiology  The inflammatory response in MS consists of predominantly lymphocytic and mononuclear cells.  the response of T- lymphocytes from patients with MS for reactivity with Myelin Basic Protein (MBP).  No specific oligoclonality was found to help differentiate patients with MS. 29Lectures: Pathology (n.d.)
    30. 30. Pathophysiology  it remains possible that other myelin proteins such as myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG), and others may also play a role in pathogenesis of MS. 30Lectures: Pathology (n.d.)
    31. 31. Pathophysiology  MS also has been associated with certain Human Leukocyte Antigen (HLA).  Different HLA associations are reported within ethnic groups and some associations remain very stable in patients with MS. 31Lectures: Pathology (n.d.)
    32. 32. Pathophysiology  It is confirmed that MHC molecules may contribute to genetic susceptibility to the disease.  DR2, DR(1*1501), DQ(1*602), DQA102 and the DW2 haplotype are frequently associated with multiple sclerosis. 32Lectures: Pathology (n.d.)
    33. 33. Pathophysiology  Virus exposure: • One possible explanation for this is molecular mimicry between viral and CNS proteins so that antiviral response is mediated against myelin. • "Molecular mimicry" means shared molecular homology between viral proteins and some normal human proteins. In MS, homology between viral peptides and myelin antigens is established. 33Lectures: Pathology (n.d.)
    34. 34. Pathophysiology • Viral persistency, latency and periodic inactivation could be of possible significance.* • Viral infections also are known to provoke relapses of the disease. 34Lectures: Pathology (n.d.)
    35. 35. Pathophysiology  Another possibility is that autoimmunity results from super antigenic stimulation of T-cells by viral or bacterial proteins.  Super antigens may bind to specific T-cell receptor proteins, producing non-specific stimulation of a large number of T-cells.  This may result in clonal expansion of T-cells reactive to myelin or oligodendrogliocyte antigens. 35Lectures: Pathology (n.d.)
    36. 36. Pathophysiology 36
    37. 37. Pathophysiology 37
    38. 38. Pathophysiology 38
    39. 39. Pathophysiology 39
    40. 40. 40 The traditional neuropathological view of MS (A) highlights CNS injury as a consequence of an autoimmune response. An alternative hypothesis (B) proposes that activation of autoimmune cells occurs as a consequence of toxic insults to CNS cells. Infections, for example, may be asymptomatic but cause cytophatic effects to target cells in the course of an antiviral response. The prolonged release of neural antigens may then induce inflammatory responses. Models of Disease Pathogenesis in MS (Hauser & Oksenberg, 2006)
    41. 41. 41 Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion. Original scale 1:100 Photomicrograph of a demyelinating MS-Lesion. Immunohistochemical staining for CD68 highlights numerous macrophages (brown)
    42. 42. 42 Demyelinization by MS. The Klüver-Barrera colored tissue show a clear decoloration in the area of the lesion Photomicrograph of a demyelinating MS-Lesion. Klüver-Barerra-Stain. Original Magnification 10x
    43. 43. 43 lesions typical of MS 1-NAWM border with the lesion 2-Lesion external layer 3-Active layer 4-Recently demyelinated tissue 5-Inactive layer Henderson et. al According with the most recent research, an active lesion is composed of different layers:
    44. 44. Pathophysiology  This is a short movie (1:58) that animates the process of demyelination; it can be very helpful.  I strongly encourage you to watch it.  If you are in slide show mode, click on this hyperlink: Or you can right click it & you will be directed there: MS pathophysiology-BBB disruption If it does not work, copy v& paste this web address: 44 This is a screenshot only and will not play the video
    45. 45. 45 HD MS animation: this is a different short animation video (2:12) with high quality graphics Click below to play the video if using slide show or (right click & select Open Hyperlink): HD MS patho video OR paste to your web address:
    46. 46. Prevalence & Morbidity  Currently 350,000 to 500,000 people in the U.S. have been diagnosed  200 people are diagnosed every week  As of 2008, 2-2.5 million people worldwide are affected  At this time, the Center for Disease Control and Prevention does not require physicians to report new cases and symptoms of the disease can go unrecognized for some time, these numbers are only estimates. 46National Multiple Sclerosis Society (n.d.)
    47. 47. Prevalence & Morbidity  Symptoms can start between 10 and 80 years of age but usually begin between the ages of 20 and 40 (mean age of 32)  Affects more women than men (almost 2 to1)  Affects Caucasians more than Hispanics or African Americans, less common in Asians  Increases the farther one travels from the equator in either hemisphere 47National Multiple Sclerosis Society (n.d.)
    48. 48. Prevalence & Morbidity  Medications used to treat MS while modestly effective can have adverse effects and be poorly tolerated. Many people pursue alternative treatments, despite a lack of evidence.  MS was first described in 1868 by Jean-Martin Charcot (1825-1893)  A number of new treatments and diagnostic methods are under development. 48National Multiple Sclerosis Society (n.d.)
    49. 49. Prevalence & Morbidity  Roughly 85% of people with MS have a relapsing- remitting course  The condition begins in 85% of cases as a clinically isolated syndrome over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 20% have more than one of the previous difficulties. 49 (National Multiple Sclerosis Society , n.d.) (Noonan (Tsang & Macdonell)
    50. 50. Prevalence 50
    51. 51. Clinical Manifestations  MS can affect any area of the brain, optic nerve, or spinal cord, causing almost any neurologic symptom.  A classic MS sign: Uthoff’s phenomenon is a worsening of symptoms in the heat.  Symptoms of relapse tend to: • Develop over a few days • Stabilize for a few weeks • Improve over weeks or months • Be followed by a period of stability (a remission) 51National Multiple Sclerosis Society (n.d.)
    52. 52. Clinical Manifestations: Signs & Symptoms Consistent with Demyelinating Disease  Visual 1. Blurred vision 2. Unilateral loss of vision 3. Oscillopsia 4. Diplopia  Motor 1. Trunk/limb weakness 2. Spascity 3. Hyperreflexia 4. Gait disturbance 5. Balance problems  Sensory 1. Numbness 2. Paresthesias 3. Dysesthesias 4. L’Hermitte’s sign (electrical sensations run down the spine when the patient bends her head forward) 5. “MS Hug” (tightening around the chest) 6. Trigeminal neuralgia 7. Proprioception deficits National Multiple Sclerosis Society (n.d.) 52
    53. 53. Clinical Manifestations: Signs & Symptoms Consistent with Demyelinating Disease  Cerebellar 1. Tremor 2. Ataxia  Genitourinary 1. Urgency/Frequency/ Retention 2. Incontinence 3. Frequent UTI 4. Constipation 5. Impotence 6. Dyspareunia  Neuropsychiatric 1. Impairment of memory, concentration, attention 2. Depression 3. Irritability 4. Anxiety  Intractable fatigue with no other cause. National Multiple Sclerosis Society (n.d.) 53
    54. 54. Diagnostics  There is not a definitive diagnostic examination to diagnose Multiple Sclerosis.  Evidence of at least two affected different regions of the central white matter affected at different times  It cannot be based on any single symptom or sign, but on a total clinical picture.  MRI (Magnetic Resonance Imaging) is used in diagnosing Multiple Sclerosis, but it should not be used as the only diagnostic test. 54(Greenberg 2012, p 237)
    55. 55. 55
    56. 56. Diagnostics  MRI evidence can take the place of clinical evidence of dissemination of lesions in both time and space.  Imaging is used to show dissemination in time if there is a gadolinium-enhancing lesion at least 3 months after the onset of the initial clinical event.  Obtaining objective evidence of dissemination of lesions in time and space is essential for the diagnosis. 56(Greenberg 2012, p 237)
    57. 57. Diagnostics 57(, n.d.)
    58. 58. Diagnostics 58(, n.d.)
    59. 59. Diagnostics 59(, n.d.)
    60. 60. Diagnostics 60(, n.d.)
    61. 61. Diagnostics 61(, n.d.)
    62. 62. Diagnostics: Dawson's Fingers appearing on an MRI scan 62 •"Dawson's Fingers" is the name for the lesions around the ventricle-based brain veins of patients with MS •The condition is thought to be the result of inflammation or mechanical damage by blood pressure around long axis of medular veins. •Dawson's fingers spread along, and from, large periventricular collecting veins, and are attributed to perivenular inflammation
    63. 63. Diagnostics  Other useful tests include cerebrospinal fluid via spinal tap or lumbar puncture. It commonly shows a mild lymphycytosis or a slightly increased protein. CSF protein electrophoresis shows the presence of discrete bands in the immunoglobulin G (IGG) region (oligoclonal bands).  For a diagnosis of primary progressive MS, an abnormal CSF finding with evidence of inflammation and immune abnormality is necessary* 63(Greenberg 2012, p 237) ((McDonald 2001)
    64. 64. Diagnostics  evidence of dissemination in space (using MRI or visual evoked potentials) and in time (using MRI or continued progression of disability for 1 year) is required. 64(McDonald 2001) (, n.d.)
    65. 65. Diagnostics  Patients are classified as having MS or not having MS; subcategories that depend on the types of study in the diagnostic workup ("clinically definite", "laboratory-supported") are unnecessary.  Draw a Vitamin D Level, as there is growing evidence that shows a low Vitamin D level may increase the risk of developing Multiple Sclerosis. The evidence suggests that Vitamin D has immunomodulatory effects on T lymphocytes similar to interferon-beta. 65(McDonald 2001) (Pierrot-Deseilligny, 2013).
    66. 66. Classification & Prognosis  MS is classified into 4 types: 1-Benign Multiple Sclerosis : • Mild infrequent sensory exacerbations with full recovery. 2-Relapsing Remitting Multiple Sclerosis: • Episodes of exacerbations and remissions during which not all symptoms resolve completely. The patient may be left with permanent disability which may vary in severity. relapses are often more severe than in the previous group. Relapses also become more severe with time. 66(, n.d.)
    67. 67. Classification & Prognosis 3-Secondary Chronic Progressive • Condition of patients with relapsing/remitting disease begins to gradually worsen over time with resulting accumulation of neurologic signs and symptoms. In this form of the disease, relapses become more severe while remissions are less complete, shorter in duration, and eventually non-existent. The course of MS becomes steadily progressive. 67(, n.d.)
    68. 68. Classification & Prognosis 4-Primary Progressive • There is no history of relapse in these patients. Disease begins with a slow progression of neurologic deficits. Problems appear and gradually worsen over time. Common problems include spastic paraparesis, cerebellar ataxia, urinary incontinence. 68(, n.d.) Click me (18 seconds long)
    69. 69. 69 (, n.d.)
    70. 70. Classification & Prognosis  Prognosis of MS: Early Onset MS vs. Adult Onset : • Early Onset MS (EOMS) seems to have a worse prognosis based upon cognitive studies & MRI results • Cerebellar/brainstem & spinal involvement were significantly higher in EOMS, compared to Adult Onset MS (AOMS) 70(Osakbas et. al, 2012) This is an interactive MRI. Watch it for 5 sec
    71. 71. Classification & Prognosis  Prognosis of MS: Early Onset MS vs. Adult Onset : • The most significant findings were the differences in the Paced Auditory Serial Addition Test (PASAT). • PASAT measures the number T1 hypointense lesions. In a 5 year study, T1 hypointense lesions were significantly higher than baseline in EOMS compared to AOMS 71(Osakbas et. al, 2012) MRI brain scan produced using a Gradient-echo phase sequence showing an iron deposite in a white matter lesion (inside green box in the middle of the image; enhanced and marked by red arrow top-left corner Disease biomarkers
    72. 72. Classification & Prognosis Good Prognosis Poor Prognosis  Optic Neuritis  Isolated sensory symptoms  Long interval to second relapse  No evidence of disability after 5 years  Female gender  ‘Multifocal’ Clinically Isolated Syndrome  Efferent (motor/cerebellar) systems  High relapse rate in 5 years  Substantial disability after 5 years  Abnormal MRI with heavy lesion load  Male gender Hassan-Smith, & Douglas 72 Prognostic Factors in Patients with Multiple Sclerosis
    73. 73. Classification & Prognosis Mortality Rates for Multiple Sclerosis  The average life span of an individual with MS is 25-35 years after initial diagnosis.  Most MS patients live into the 7th decade  Studies have shown that individuals with MS die around 10 years earlier than the general population 73 (Overcoming Multiple Sclerosis, n.d.) (Multiple Sclerosis: Prognosis. n.d.) Disability-adjusted life year for multiple sclerosis per 100,000 inhabitants in 2004
    74. 74. Classification & Prognosis  Mortality Rates for Multiple Sclerosis  -Studies have indicated that MS is not a cause of death, whereas deaths occur as a result of other chronic complications resulting from immobility, chronic urinary tract infections, dypsnea, dysphagia, aspiration & bacterial pneumonia 74(Osakbas et. al, 2012)
    75. 75. Treatments  There are several disease modifying therapies for relapsing forms of Multiple Sclerosis (Relapsing and remitting MS, Secondary progressive MS with exacerbations) available in the United States (Hauser, 2006)  Some therapies are FDA approved while some are still experimental  Some unconventional treatment modalities are based on etiologies that are not recognized by the medical community as a whole and thus are controversial 75
    76. 76. Treatments 76 FDA-Approved Disease-Modifying Agents: Aubagio (teriflunomide) Avonex (interferon beta-1a) Betaseron (interferon beta-1b) Copaxone (glatirmer acetate) Extavia (interferon beta -1b) Gilenya (fingolimod) Novantrone (mitoxantrone) Rebif (interferon beta -1a) Tecfidera(dimethylfumarate) Tysabri (natalizumab) (MS Society, 2013)
    77. 77. Treatments  For an acute episode of Multiple Sclerosis including relapse the treatment of choice is steroids. Methylprednisolone 1 Gram may be administered intravenous for 3 to 5 days.  Other treatment choices include Prednisone 1000mg daily for 3 to 5 days or Dexamethasone 160mg daily for 3 to 5 days oral administration. 77(Greenberg, 2012)
    78. 78. Treatments  For Relapse Prevention, first line treatment choices include: Interferon Beta 1a ( Rebif) 44 mcg subcutaneous (s/q) three times per week Beta 1a (Avonex ) 30mcg Intramuscular once weekly Beta 1b is (Betaseron, Extavia 0.25 mg) (s/q) every other day, Glatiramer acetate (Copaxone 20 mcg) (s/q) daily or Fingolimod (Gylenya) 0.5 mg PO daily 78(Greenberg, 2012) Irritation zone after injection of glatiramer acetate
    79. 79. Treatments  Other treatment choices for relapse prevention despite use of first line treatment include: Natalizumab (Tysabri) 300mg IV monthly Fingolimod 0.5mg daily orally Mitoxantrone 12mg every 3 months. For enhancing lesions the best treatment of choice is Natalizumab (Tysabri) 300 mg IV monthly. Alemtuzumab (Campath, under development as Lemtrada) used under clinical trial protocols 79(Greenberg, 2012) Chemical structure of alemtuzumab
    80. 80. Treatments Adjuvant Therapy:  As per Pierrot-Deseilligny (2013) Vitamin D supplementation may attenuate the progression of MS or Vitamin D supplementation may prevent the development of MS and/or attenuate its progression.  Provigil 200mg daily for energy  Modafinil 200 mg daily produced significant improvement in fatigue. 80(Greenberg, 2012)
    81. 81. Non-FDA approved & Experimental Treatments:  Juicing raw organic vegetables and fruits.  An experimental treatment that involves injecting multiple-sclerosis (MS) patients with their own white blood cells has been shown to be safe, according to a new study. The study also provided some evidence that the treatment was effective in modifying the immune system. "What we are doing is essentially tricking the immune system," into thinking myelin is no longer a threat, said study researcher Stephen Miller, a professor of microbiology and immunology at Northwestern University Feinberg School of Medicine in Chicago. (Gholipour, 2013) 81
    82. 82. Non-FDA approved & Experimental Treatments:  Chronic Cerebrospinal Venous Insufficiency (CCSVI) is when portions of the venous system (the body's network of large and small veins) in the head and neck are narrowed or blocked and therefore unable to efficiently remove blood from the brain and spinal cord (central nervous system). 82
    83. 83. Non-FDA approved & Experimental Treatments:  Dr. Zamboni's initial hypothesis suggested that because these compensatory blood vessels don't have the same wall integrity as larger veins, they tend to leak blood into the adjacent tissue, depositing iron in the central nervous system and thereby triggering an immune response associated with multiple sclerosis. 83(Fankhauser, 2013)
    84. 84. Non-FDA approved & Experimental Treatments: 84
    85. 85. Non-FDA approved & Experimental Treatments:  Controversy over findings 85
    86. 86. Non-FDA approved & Experimental Treatments:  Confirmation by radiology: 86
    87. 87. Non-FDA approved & Experimental Treatments: 87(Zamboni et. al, 2009)
    88. 88. Non-FDA approved & Experimental Treatments: 88(Zamboni et. al, 2009)
    89. 89. Non-FDA approved & Experimental Treatments: 89(Zamboni et. al, 2009)
    90. 90. Non-FDA approved & Experimental Treatments: 90(Zamboni et. al, 2009)
    91. 91. Non-FDA approved & Experimental Treatments: The Chlamydia Pneumoniae debate: Theory Opponents  According to Fainardi et. Al (2008), “there is no current evidence supporting a causal role of C. pneumoniae in MS since, while some studies suggest a role of C. pneumoniae only as a CNS innocent bystander epiphenomenon promoted by overactive chronic inflammation operating in MS”. 91(Fainardi et. al, 2008)
    92. 92. Non-FDA approved & Experimental Treatments:  Others indicate a role of C. pneumoniae as a cofactor in development and progression of the disease in a subset of MS patients.  “Excluding a potential role of C. pneumoniae in MS pathogenesis may be an oversimplification since direct evidence of CNS C. pneumoniae infection is difficult to demonstrate”.  The actual involvement of C. pneumoniae in MS still inconclusive. More studies are needed 92 (Fainardi et. al, 2008)
    93. 93. Non-FDA approved & Experimental Treatments: Theory Advocates:  A controversial expose was broadcasted on ABC news (UK)  It is a bit long (14:o9) but is very amusing. It shows an infectious disease Dr. who cured his wife’s MS?  Treating with antibiotics? He presents a very convincing theory. You have to see it for yourself before you judge. 93
    94. 94. Non-FDA approved & Experimental Treatments:  To watch “MS cure?” Click here: MS Cure? Or Paste this in your window: 94 These are just screenshots & will not open the video
    95. 95. Resources Available 95 In 2006, Ohio declared March MS Awareness Month. Now each year at this time they come together to celebrate their accomplishments and to recognize the challenges faced. This is a video (2:43) for MS Awareness month. It is presented in a drawing/cartoon format and is easy to comprehend by the general public. Use the Hyperlink: MS Oversimplified OR Paste this link:
    96. 96. Nutrition and Supplements  A main focus for MS patients is intake of foods that lower inflammation, not aggravate it. • Polyphenols (including flavonoids and nonflavonoids) and carotenoids: vegetables, fruits, wine, spices, and herbs • Polyunsaturated fats , omega-3 fatty acids and DHA: olive oil, oily fish, fish oil.  Limiting saturated fats of animal origin  limit caffeine consumption to decrease bone mineralization loss 96(Swank & Goodwin, 2003) (Riccio et al, 2010)
    97. 97. Nutrition and Supplements  Vitamin B12 deficits is associated with demyelination of nerve fibers so supplementation of Vitamin B12 and Vitamin B complex assists in prevention.  Calcium supplementation is important as the incidence of osteoporosis , related to decreased mobility, is higher in MS patients.  vitamin D, selenium, and zinc have all been found to decrease the production of inflammatory molecules associated with MS as well. 97(Riccio et al, 2010)
    98. 98. Social Stigma  The amount of stigma associated with chronic neurological illness is determined by two separate and distinct components: the attribution of responsibility for the stigmatizing illness and the degree to which it creates discomfort in social interactions. (WHO, 2002) 98
    99. 99. Social Stigma  The socially structured stigma indicates that individuals who are chronically ill will have less “social value” than healthy individuals. 99
    100. 100. Social Stigma  Stigmatized individuals are often rejected by neighbors and the community, and as a result suffer loneliness and depression. “The psychological effect of stigma is a general feeling of unease or of “not fitting in”, loss of confidence, increasing self-doubt leading to depreciated self- esteem, and a general alienation from the society.” (Guilbert, 2003) 100
    101. 101. Social Stigma  Multiple sclerosis has a profound impact on patients’ social roles and the well-being of their families. Varying degrees of functional decline typically accompany MS. Because the onset is usually at about 30 years of age, the loss in productivity of people with MS can be substantial. 101
    102. 102. Social Stigma  Functional decline will often interfere with the opportunities for people with MS to perform their customary roles. 102
    103. 103. Social Stigma  Physical disability: complicated by fatigue & depression  Possibly cognitive impairment: contributes to an unemployment rate as high as 70% among people with MS  To replace lost earnings, they frequently collect disability benefits and social welfare. 103
    104. 104. Social Stigma  People with MS: - Use more health-care resources than the general population. - Bear a financial burden related to home and transport modifications and the need for additional personal services. 104
    105. 105. Social Stigma  The ability to continue in gainful employment or to maintain social contacts and leisure activities correlates with the course and severity of the disease and cognitive function. 105
    106. 106. Social Stigma  MS will usually have a substantial adverse effect on a person’s quality of life. Improving quality of life should be a key goal of people with MS.  The following is a very touching clip that was put together by an MS patient showing the burden of MS (slides & music) “This is how I experience MS”  MS Society stated “We like this video! Simple but effective and powerful”  Paste this link in your window: 106
    107. 107. Resources Available 107 •MS One to One •MS ActiveSource® | •Betaseron •Shared Solutions •Gilenya •Rebif/MS LifeLines | •MS ActiveSource •Tysabri
    108. 108. Resources Available 108 •Multiple Sclerosis International Federation (MSIF)* website: • For information on patient assistance programs, visit
    109. 109. Resources Available 109 The Multiple Sclerosis Emerging Therapies Collaborative —which includes the MS Coalition, the American Academy of Neurology, the VA Multiple Sclerosis Centers of Excellence East and West, and ACTRIMS * Visit their Website at:
    110. 110. Case Study (word doc. Will be posted as well) 110 Lisa is a 33 year old white female who resides in the Faroe Islands. She works as an IT network engineer and spends hours in front of a computer. She began to notice that she was having blurred vision, and brushed it off as eye strain. She reports that she has been working very hard which left her under a lot of stress. She got sick with a flu and her neurologic condition worsened. A few weeks passed and she began to experience numbness and tingling in her right arm. She had no idea what was causing this sensation, but attributed it to possibly doing some heavy lifting at the gym. The next morning, Lisa tried to open the door to her office, but weakness in her right arm prevented her from doing so. She also noticed that she was having difficulty maintaining her balance when walking that did not resolve. As weeks went by, her symptoms began to get worse. Lisa finally decided to make an appointment with her doctor for further evaluation.
    111. 111. Past Medical & Surgical History 111 Significant for mumps and chicken pox as a child, and anemia and allergies with hives later in life. She also had a tubal ligation. The patient relates that for many years she had noticed some transient but significant changes in neurologic functions, particularly heat intolerance precipitating a stumbling gait and a tendency to fall, which she would attribute to long term sun exposure & dehydration. She is sexually active and reports frequent UTIs
    112. 112. Physical Exam and Laboratory Findings 112 -Neurological Exam is performed. Mild paraparesis is noted in both arms, without severe spacicity. -Cranial Nerves III, IV, & VI: Decreased hearing is noted on the right. The Weber test reveals greater conductance on the left. Swallow reflex is absent. -Sensory exam reveals a decreased sensation to pins on the left foot. Gait is mildly unstable. -Upon examination of the back of the eyes with an opthalmoscope, the optic disk appears to be irritated, indicating inflammation of the optic nerve. -Magnetic Resonance Imaging (MRI) detects multifocal white matter disease and areas of increased T2 signal in both cerebral hemispheres. -Following Lumbar Puncture (LP), the protein content of the fluid is higher than normal, CSF protein electrophoresis analysis pending
    113. 113. Points To Ponder 113 P.T.P. 1- In the light of any risk factors present (list these), what is the probable diagnosis of Lisa & why? PTP 2: Describe the process of blood-Brain disruption in MS briefly PTP 3:What are the most common signs & symptoms that appear early in the course of MS? PTP 4: What general recommendations would you give to this patient? Suppose that this patient is considering having a child. How would you counsel her for or against another pregnancy?
    114. 114. References: 1. Hall, J. E., & Guyton, A. C. (2011). Textbook of Medical Physiology (12th ed.). Philidelphia, PA: Saunders Elsevier. 2. Correale J, Villa A. The blood-brain-barrier in multiple sclerosis: functional roles and therapeutic targeting. Autoimmunity. 2007 Mar;40(2):148-60. Review. 3. Epidemiology of MS (n.d.). Retrieved July 6, 2013, from ms/who-gets-ms/epidemiology-of-ms/index.aspx 4. Fankhauser, G. T., Stone, W. M., Fu, R., & Money, S. R. (2013). Spiral vein graft for internal jugular bypass in a patient with multiple sclerosis and suspected chronic cerebrospinal venous insufficiency. Annals of Vascular Surgery, 27(5), 673.e5-673.e8. doi:10.1016/j.avsg.2012.05.033 114
    115. 115. 5. Cristante E, McArthur S, Mauro C, Maggioli E, Romero IA, Wylezinska-Arridge M, Couraud PO, Lopez-Tremoleda J, Christian HC, Weksler BB, Malaspina A, Solito E. Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications. Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):832-41. doi: 10.1073/pnas.1209362110. 6. Fainardi E, Castellazzi M, Seraceni S, Granieri E, Contini C. Under the microscope: focus on Chlamydia pneumoniae infection and multiple sclerosis. Curr Neurovasc Res. 2008 Feb;5(1):60-70. Review. DOI: 10.2174/156720208783565609 7. Gholipour,B. 2013 LiveScience: new multiple sclerosis treatment 'tricks' immune system. Retrieved from sclerosis-treatment-immune-system-_n_3397059.html 115
    116. 116. 8. Greenburg, D.A., Aminoff, M.J., & Simon, R.P. (2012). Clinical neurology. Hightstown, NJ: McGraw-Hill. 9. Guilbert, J. (2003). The world health report 2002 - reducing risks, promoting healthy life. Education for Health: Change in Learning & Practice (Taylor & Francis Ltd), 16(2), 230-230. Retrieved from direct=true&db=rzh&AN=2009386717&site=ehost-live&scope=site 10. Gutiérrez J, Linares-Palomino J, Lopez-Espada C, Rodríguez M, Ros E, Piédrola G, del Maroto MC. Chlamydia pneumoniae DNA in the arterial wall of patients with peripheral vascular disease. Infection. 2001 Aug;29(4):196-200. DOI: 10.1007/s15010-001-1180-0 116
    117. 117. 11. Hassan-Smith, G., Douglas, M.R., (2011). Management and prognosis of multiple sclerosis. British Journal of Hospital Medicine, (72) 11, p. M174-M176 12. Hauser, S.L., Josephson,S.A., English,J.D., & Engstrom,J.W. 2006 Harrison’s Neurology in Clinical Medicine Hightstown, NJ: McGraw-Hill. 13. Hauser SL, Oksenberg JR. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron. 2006 Oct 5;52(1):61-76. Review. 14. Henderson AP, Barnett MH, Parratt JD, Prineas JW. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann Neurol. 2009 Dec;66(6):739-53. doi: 10.1002/ana.21800. 15. Lectures: Pathology (n.d.). Retrieved July 9, 2013, from 117
    118. 118. 16. McDonald, W. I., Compston, A., Edan, G., Goodkin, D., Hartung, H.-P., Lublin, F. D., McFarland, H. F., Paty, D. W., Polman, C. H., Reingold, S. C., Sandberg-Wollheim, M., Sibley, W., Thompson, A., Van Den Noort, S., Weinshenker, B. Y. and Wolinsky, J. S. (2001), Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol., 50: 121– 127. doi: 10.1002/ana.1032 17. Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler. 2003 Dec;9(6):540-9. Review. 18. MS prevalence (n.d.). Retrieved July 6, 2013, from 19. Multiple sclerosis: answers at your fingertips (2010). Practice Nurse 39(7); 27-9. Retrieved from b1faf4866de3b498%40sessionmgr4&vid=10&hid=9&bdata=JnNpdGU9ZWhvc3QtbGl 2ZSZzY29wZT1zaXRl#db=rzh&AN=2010638609 118
    119. 119. 20. Multiple Sclerosis: Prognosis. (n.d.). Retrieved July 8, 2013, from 21. National Multiple Sclerosis Society, General Information. (2013). The MS Disease Modifying Medications. Retrieved from 22. Noonan C.W., Williamson, D.M., Henry, J.P., Indian, R., Lynch, S.G., Neuberger, J.S. (2010). The prevalence of multiple sclerosis in 3 US communities. Preventing Chronic Disease, 2010;7(1):A12. Retrieved from 23. Osakbas, S., Kaya, D.. & Idiman, E. (2012). Early onset multiple sclerosis has worse prognosis than adult onset multiple sclerosis based on cognition and magnetic resonance imaging. Autoimmune Diseases, 2012; doi:10.1155/2012/563989 24. Overcoming Multiple Sclerosis. MS course & prognosis. (n.d.). Retrieved July 8, 2013, from MS/Course-and-Prognosis/ 119
    120. 120. 25. Pierrot-Deseilligny, C., & Souberbielle, J. (2013). Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis. Therapeutic Advances In Neurological Disorders, 6(2), 81-116. doi:10.1177/1756285612473513 26. Polman, C. H., Thompson, A. J., Murray, T. J., & McDonald, W. I. (2001). Multiple sclerosis: The guide to treatment and management. New York, New York: Demos Medical Publishing. Retrieved from direct=true&db=rzh&AN=2009273592&site=ehost-live&scope=site 27. Riccio, P., Rossano, R., & Liuzzi, G. M. (2010). May diet and dietary supplements improve the wellness of multiple sclerosis patients? A molecular approach. Autoimmune Diseases, 2010(2010). 28. Rolak, L. A. (2003, January 1). Multiple sclerosis: It’s not the disease you thought it was. Clinical Medicine & Research, 1(1), 57-60. 120
    121. 121. 29. Signs & Symptoms Consistent With Demyelinating Disease (n.d.). Retrieved July 6, 2013, from resources-and-tools/core-curriculum/diagnosing-multiple-sclerosis/signs-symptoms- consistent-with-demyelinating-disease/index.aspx 30. Swank, R., & Goodwin, J. (2003, February). Review of MS patient survival on a Swank low saturated fat diet. Nutrition, 19, 161-162. Retrieved from 31. Tsang BK, Macdonell R. Multiple sclerosis- diagnosis, management and prognosis. Aust Fam Physician. 2011 Dec;40(12):948-55. 32. What causes MS? (n.d.). Retrieved July 3, 2013, from ms/what-causes-ms/index.aspx 121
    122. 122. 33. What we know about MS: Symptoms (n.d.). Retrieved July 6, 2013, from ms/symptoms/index.aspx 34. Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'Ara S, Bartolomei I, Salvi F. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):392-9. doi: 10.1136/jnnp.2008.157164. ------------------------------------------------------------------------------------------------ Too much info? Thank you for your attention & efforts … For answers to the case study, email 122