Multiple SclerosisBy Kelsey Walker

Topics to Discuss…

•Definition of MS•Statistics•Types of MS•Being Diagnosed with MS•Signs & Symptoms•Treatment Options•Scientific Progression•Living with MS

~Multiple Sclerosis~• Number (multiple) + Condition (sclerosis):

Greek “scarring/hardening” • Chronic neurological disorder affecting the

CNS • Possible autoimmune disorder

Scientifically….What’s Happening??

• Inflammation in white matter of CNS called plaques

• Myelin (fatty insulation of nerve cell fibers in brain & spinal cord) are destroyed

• Neurological transmission of impulses are slowed or blocked

• Results in lost function

White Matter

• Myelinated axon bundles and glial cells in CNS

• AKA: bundle, fasciculus, lemniscus

• PNS: collection of axons “nerve”

Demyelinating Lesions

• 51 y/o Pt• 2 yr. Hx of

Rheumatoid Arthritis• Developed lesion

Post taking

Etanercept

Importance of Myelin• Insulating sheath surrounds nerve cell

axons

• Consists of two protein layers (20% protein, 80% lipid- phospholipids, glycolipids, and cholesterol )

• Facilitates smooth high speed transmission of electrochemical messages

• Produced by oligodendrocytes in CNS and Schwann cells in PNS

Myelin Images

Causes of MS????• Exact cause unknown…studies

constantly being conducted AutoImmune: own immune system launches defensive attack on own tissues

Environmental: viral, toxic, nutritional, previous trauma injury

Genetically Inherited: races develop MS differently

Geographically: climate element

AutoImmune …Healthy Immune System: antigens trigger a response. Body stores few cells for each antigen. T Cells: patrol for antigens, surface carries receptor molecules to detect.

Regulatory T Cells (assist in making antibodies)

Helper T Cells (activate the defense)

Killer T Cells (attack disease or damaged cell by binding and inducing cytokines)

AutoImmune Continued• In MS, immune system is unable to properly identify

its T Cells. The myelin is unrecognizable and begins to be destroyed.

• Studies: myelin basic protein (component of myelin) when injected into lab animals, can develop experimental allergic encephalomyelitis (EAE), a brain and spinal cord disease similar to MS.

• Studies: BBB, possible immune system components pass barrier and result in NS damage

• Studies: Viral infections, produce gamma interferon (naturally occurring chemical) worsens MS. Possible viral infections may lead to MS?

Nat’l MS Society Discovery• Molecule aryl hydrocarbon receptor (AHR)

responsible in aiding the immune system to respond to environmental toxins regulates balance between inflammatory and anti-inflammatory cells in mice with diseases similar to MS.

• TH(helper)17 cells cause inflammation• TReg Cells suppress attack• MS TR cells fail• AHR are located on surface of these TH17 & TR

cells• Discovery is Key in understanding why different

chemicals affect AHR and apply this to therapies for autoimmune diseases

Genetics…• Ethnicity: Gypsies, Eskimos, Bantus show no case of

developing MS• Native Indians in North and South America,

Japanese, Asians indicate low incident rates• Chance of developing MS is less than a tenth of one

percent. • Family: First degree relatives have 1-3% chance of

getting MS. Identical Twins 30% if one twin has MS, fraternal 4%

• Studies: human leukocyte antigen (HLA) “major histocompatibility complex” on chromosome 6 (genetically determined proteins influencing immune system)

HLA…support that MS is result of several factors

• HLA Patterns differ in patients with MS• Research in northern Europe and America

revealed 3 HLAs more prevalant in MS Pts. • Exhibit the 3 HLAs in combinations….MS Pts

have more than one of those possibilities. • Different combinations may result in various

disease severity and progression• Comparing mice with EAE & humans with MS

reveal susceptibility to disease on Chromosome 5, and regions on 2,3,7,11,17,19,X

Chromosome 6• Sept 28, 2005 San Diego article claims

“most comprehensive genetic study to date of MS has pinpointed a cluster of genes on chromosome 6 as playing the major role in causing the disorder”

Geographically• More common at northern and southern latitudes

versus around the equator. • Possible environmental exposure prior in life plays a

role in triggering MS. • Five times more prevalent in temperate climates

(northern U.S., Canada, Europe) than tropical regions.

• People who move to different climates after age 15 maintain the risk in which they grew up in.

• Indicate possible infection with long latency period during puberty, contact with unknown protective agent, or an ethnic susceptibility factor.

Interesting Fact!!Reports of MS “clusters”, most famous epidemic…Faeroe Islands north of Scotland following the arrival of British troops during WWII.

Resulted in 32 cases of MS from 1943 until 1973

Statistics• Most symptoms occur between 20 and 40 years of age• Diagnosis is often delayed, MS may go asymptomatic for

several years• Symptoms rarely begin before age 15 and after age 60;

however, there are exceptions• Whites are twice as likely to develop MS• Women develop MS almost twice the rate of men• About 250,000-350,000 people in U.S. have been

diagnosed with MS by a physician.• Known cases 50,000 in Canada, 130,000 in Germany,

85,000 in UK, 75,000 in France, 50,000 in Italy, and 11,000 in Switzerland.

• Approximately 200 new cases are diagnosed each week.

Science…A Lifelong discovery

•1946 Nat’l MS Society; 1947 Society sponsored by first 3 research projects. Today over $600 million investment has been put into research.

•In 2008, 136 clinical trials were initiated

The Myelin Project for Research & Education in Demyelinating

Diseases• Est. 1989, goal of funding research to find a cure for

demyelinating diseases. • Founded by Augusto Odone and wife Michaela. Son

Lorenzo suffers from X-linked adrenoleukodystrophy. • Film “Lorenzo’s Oil” released 1992 tells the Odone’s

struggles. • Branches in Germany, Italy, Canada, UK, and

partnership with European Lekodystrophy Association in France. Board members are all volunteer.

• Funds targeted towards orienting experiments• “We are not here to stay, but are working very hard to

put ourselves out of business and demolish the project as soon as possible” Myelin Project.

Diagnosing MS• Tools in assisting physicians: MRI (IV

gadolinium helps ID brain plaques), electro-physiological test (examine impulses traveling through nerves), CSF (ID abnormal chemicals)

• Requires clinical (Hx & Neurological exam) & a paraclinical (MRI, Spinal Tap) for evidence

• Hx surgeries, illnesses, allergies, family Hx, geographic living locations, medications, substance abuse, temperature influence symptoms

Diagnosis• Neurological exaggerated reflexes,

Babinski’s (upward movement of big toe once sole of foot is stimulated), eye exam (optic nerve damage)

• Must find lesion or plaques in at least two distinct areas of CNS white matter

• Rule out other possibilities

• Diagnosis is correct only 90-95% of the time…

What Diagnosis Test Results Indicate

• MRI: locates CNS lesions. Gadolinium contrast can distinguish new from old plaques.

• MRS (spectroscopy): measure brain chemical N-acetyl aspartate. Decreased levels indicate nerve damage.

• MTI (magnetization transfer imaging): white matter abnormalities. Calculates free water in tissues. Damaged nerves and demyelination show increased levels

Diagnostic Tests Continued

• DT-MRI (diffusion-tensor): measures motion of water molecules by mapping the diffusion to produce 3-D images revealing size/location of demyelinated areas.

• Functional MRI: measures physical changes in brain (blood flow) and mental function using radio waves

• VEP (visual evoked potential): measure speed of brain response to visual stimuli

• CSF: indicates cellular/chemical abnormalities, such as increased WBC count and amount of protein (myelin basic protein & immunoglobulin G antibody)

Possible Diseases Mistaken for MS

• Polyarteritis, lupus erythematosus, syringomyelia, tropical spastic paraparesis, cancers, tumors compressing brainstem/spinal cord (mimic lesions of white matter)

• Progressive multifocal leukoencephalopathy (mimic acute stage)

• R/O stroke, neurosyphilis, spinocerebellar ataxias, pernicious anemia, diabetes, Sjogren’s disease, Vit B12 deficiency

• Possible infection of Epstein-Barr/ Herpes simplex B virus

So…What are the Symptoms?• Visual Disturbances (color desaturation or monocular blindness)

• Muscle weakness• Balance/Coordination difficulty• Muscle spasm, stiffness, fatigue, numbness, prickling pain• Loss of sensation, speech impediment (articulation), tremors, dizzy• 50% Pt experience mental changes• Decreased concentration, attention deficits, memory loss, impaired

judgment, inability to perform sequential tasks• Depression (manic depression, paranoia), uncontrollable laugh/weep

(demyelination of brainstem controlling facial expression and emotions seen in severe cases)

• Sexual dysfunction• Loss of bowel/bladder control• Heat increases severity of symptoms in 60% of Pts • Optic neuritis in 55% of Pts, 1st symptom in 15% of Pts • Hearing loss • Lhermitte’s Sign (shooting electrical sensation down back of body in neck

flexion) • Symptoms Depend on area in which lesion has developed, may be

mild/severe, short/long duration depending on part of NS affected

Types of MS• Relapsing-remitting (RR) MS = series of

attacks followed by complete/partial remission, symptoms return after a period of stability.

• Primary Progressive (PP) MS = gradual clinical decline with no remission, may be temporary relief from symptoms.

• Secondary-Progressive (SP) MS = relapsing-remitting course followed by primary-progressive course.

• Chronic Progressive MS = PP,SP, PR together

Course of MS• 21% of MS Pts have benign form

(symptoms show little to no progression after initial attack)

• Malignant MS (gradual decline causing significant disability or death post disease onset)

• Development of lesions throughout the disease does not always cause symptoms. Scientists are able to estimate age of lesions through MRI

Course of MS• MRI = bright spots on T2 MRI indicate

lesions

• BBB breakdown is believed to be first step in developing lesions

• Injection of gadolinium (chemical contrast) shouldn’t cross BBB. T1 Scan revealing bright areas indicates recent disease activity

Treatment Options• Disease modifying Drugs/Interferons• Chemotherapy Drugs• Plasmapheresis• Bone marrow transplantation • Symptomatic Therapies• Immunoglobulins• Steroids• Homeopathy• Traditional Chinese Medicine• Acupuncture• Chiropractic Treatment• Energy, Vedic Medicine• Apitherapy• Diet

Disease Modifying Drugs…• Regulates the immune system. Been used since

1993 for MS known as interferons• Believed to inhibit gamma interferon and supress

the immune system, decreasing myelin destruction

• Pts have less relapses/longer interval between relapses

• Possible S/E– flu like symptoms, fever, tiredness, weakness, headaches, abnormal liver tests, injection site reaction

• Regular liver tests and blood counts is recommended if on medication

• Types: Avonex beta 1a (IM 1x/wk), Rebif beta 1a (SQ 3x/wk), Betaseron beta 1b (SQ q 2days)

Monoclonal antibodies• Alter Pt immune response, specific for a

single antigen

• Tysabri (natalizumab) reduces number of attacks with relapsing forms

• In 2004, drug was linked to PML (progressive multifocal leukoencephalopathy) (a neurological disease) and was removed from market. In 2006 FDA approved for the sale of the drug under strict guidelines.

Steroids• Solumedrol, Decadron, Prednisone,

adrenocorticotropic hormones (IV/PO)

• Shorten duration, reduce severity of attack

• Believed to restore BBB

• SE– acne, weight gain, seizures, psychosis

Chemotherapeutics• Clycophosphamide (Cytoxan),

methotrexate (Matrex), mitoxantrone (Novantrone)

• Used in severe forms of MS

• May slow down progression

Plasmapheresis

• Blood is removed and plasma separated that may contain antibodies/immunoglobulins, replaced with an artificial plasma. Plasma is then transfused back into patient

• Still an experimental treatment

• Used for secondary progressive MS

Bone Marrow Transplantation

• Infusions of own bone marrow that’s extracted and treated.

• Common for cancers in conjunction with chemotherapy

• Have showed good results in less severe MS cases; however, few have died

Homeopathy• First introduced several hundred years

ago. Two centuries ago, German physician experimented with remedies

• Discovered smaller substance doses were more effective than large doses

Traditional Chinese Medicine

• Using mostly natural origin remedies in which every patient is treated differently even if they may have the same condition

• Preparations contain several components at different ratios

• Case of concern– preparation containing ephedrine which can cause heart palpitations

Acupuncture & Chiropractic

• Acupuncture… insertion of fine needles along lines of “chi” (energy flow in the body)

• Chiropractic… relieving pain/dysfunction of misaligned vertebrae. Mostly symptomatic relief

Energy, Vedic , & Apitherapy Medicine

• Energy– reiki, craniosacral therapy, reflexology.

• No studies prove effective

• Vedic– natural medicine to balance health and relieve symptoms. Oldest medical system beginning in India. Vary from dietary, exercise, meditation, herbs, oils

• Apitherapy– Stung by bees or injected with venom

Symptomatic Relief• Spasticity- muscle relaxants(Baclofen,

Tizanidine, Diazepam, Clonazepam, Dantrolene)

• Optic Neuritis- (Oral steroids, Solu-Medrol) • Fatigue- (antidepressants, Amantadine,

Pemoline) • Pain- (ASA, antidepressants, codeine)• Trigeminal neuralgia- intense pain

(Carbamazepine, anticonvulsant)• Sexual Dysfunction- (papaverine injections)

vasodilator

Common Medication Usages

• Fatigue• Constipation• Erectile Dysfunction• N/V, dizziness• Paroxysmal itching• UTI• Disease modifying • Depression, Pain• Urinary Frequency• Acute exacerbations• Spasticity• Bladder dysfunction• Tremors

Natural Treatments• Swank Diet: reducing saturated fat intake due to

a study of populations diet• MacDougall Diet: anti-inflammatory, avoiding

alcohol, sugar, processed foods, dairy, wheat, glutinous grains, animal products and eating fresh vegetables and plenty of water

• Keep in mind there are several treatment options to reduce symptoms and slow progression of MS, but there is still NO cure for the demyelinating disease

In Conclusion• There are several research projects being

conducted in hopes of finding a treatment to stop the progression of MS.

• Science is constantly evolving• YOU can make a difference!

References• Accelerated Cure Project for MS Committee. “So You Have MS…What’s

Next?” December 2005. 18 December 2008. http://www.acceleratedcure.org• Health Communities. “Multiple Sclerosis: Natural Treatments.” 2000. 18

December 2008. http://www.neurologychannel.com• Laino, Charlene. “Multiple Sclerosis Gene Cluster Pinpointed.” WebMD Health

News. 28 September 2005. 18 December 2008. http://www.webmd.com/multiple_sclerosis

• MS Focus. “How MS is Diagnosed.” 18 December 2008. http://www.msfacts.org/info_diagnosed.php

• “Multiple Sclerosis Causes, Types, Symptoms, Diagnosis, Treatment and Prognosis Information.” 19 November 2007. 18 December 2008. http://www.medicinenet.com

• National Multiple Sclerosis Society. “How Far We’ve Come.” 18 December 2008. http://www.nationalmssociety.org

• National Multiple Sclerosis Society. “Medications Used in MS.” 18 December 2008. http://www.nationalmssociety.org/about-multiple-sclerosis/treatments/medications/index

• National Institute of Neurological Disorder & Stroke. “MS: Hope Through Research.” September 1996. 18 December 2008. <http://www.ninds.nih.gov/disorders/multiple_sclerosis>

References• News Detail. National Multiple Sclerosis Society. “Molecule Strikes Balance

in Immune System and May Be Key to Autoimmune Attack in MS.” 19 June 2008. 18 December 2008. <http://www.nationalmssociety.org>

• Ringold, Sarah M.D. “Multiple Sclerosis.” JAMA. Volume 296, No.23. 20 December 2006. 18 December 2008. http://www.jama.com

• Saladin, Ken. “Anatomy and Physiology: The Unity of Form and Function.” Fourth Edition. McGraw-Hill Companies. New York, 2007.

• The Myelin Project for Research & Education in Demyelinating Diseases. “The Myelin Project.” 18 December 2008. http://www.myelin.org

• Wolinsky, Jerry M.D. National Multiple Sclerosis Society. “Can Progressive MS Be Treated?” 18 December 2008. <http://www.nationalmssociety.org>