Download Multiple Sclerosis - faculty at Chemeketa

Multiple Sclerosis
By 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 antiinflammatory 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 = relapsingremitting course followed by primaryprogressive 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-multiplesclerosis/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>