Multiple sclerosis adjusted to publish

Presented by:
Ahmad
Amirdash, BBA, BSN, CCRN
1

 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

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

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.

 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
(med.utah.edu, n.d.)

 This “saltatory conduction” increases the velocity of
myelinated fiber transmission as much as 5-50 fold.
8(Hall & Guyton, 2011) (med.utah.edu, n.d.)

 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.

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)

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) (med.utah.edu, n.d.)

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)

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.)

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.)

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.

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.

18Schematic sketch showing constitution of blood vessels inside the brain

19
Part of a network of capillaries supplying
brain cells
A cortical microvessel stained for blood–
brain barrier protein ZO-1

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.

21
The astrocytes type 1 surrounding capillaries in the brain

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)

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)

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)

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.

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

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.

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.

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.

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.

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.

Pathophysiology
• Viral persistency,
latency and periodic
inactivation could be
of possible
significance.*
• Viral infections also
are known to
provoke relapses of
the disease.

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.

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
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
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
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:

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:
http://www.youtube.com/watch?v=K8R5N7ZMlNk
44
This is a screenshot only and will not play the video

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:
http://www.polygonmedical.com/neurology.html

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.)

 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

 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.

 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 et.al) (Tsang & Macdonell)

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)

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

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

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)

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)

Diagnostics
57(med.utah.edu, n.d.)

Diagnostics

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

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)

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) (med.utah.edu, n.d.)

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).

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.

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.

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.
Click me (18 seconds long)

 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

 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
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

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

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

 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

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

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)

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)

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

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

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)

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

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

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)

Treatments:
84

Treatments:
 Controversy over findings
85

Treatments:
 Confirmation by radiology:
86

Treatments:
87(Zamboni et. al, 2009)

Treatments:

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)

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)

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

Treatments:
 To watch “MS cure?” Click here: MS Cure?
Or Paste this in your window:
http://www.abc.net.au/catalyst/stories/3572695.htm
94
These are just screenshots & will not open the video

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:
http://www.youtube.com/watch?v=Naecv3h868c

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)

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)

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

Social Stigma
 The socially
structured stigma
indicates that
individuals who
are chronically ill
will have less
“social value” than
healthy
individuals.
99

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

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

Social Stigma
 Functional decline
will often interfere
with the
opportunities for
people with MS to
perform their
customary roles.
102

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

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

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

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:
http://www.youtube.com/watch?v=PtmuaSVHYLM
106

Resources Available
107
•MS One to One
MSOnetoOne.com
•MS ActiveSource®
avonex.com |
msactivesource.com
•Betaseron
betaseron.com
•Shared Solutions
sharedsolutions.com
•Gilenya
gilenya.com
•Rebif/MS LifeLines
rebif.com | mslifelines.com
•MS ActiveSource
msactivesource.com
•Tysabri
tysabri.com

Resources Available
108
•Multiple Sclerosis International Federation (MSIF)*
website: http://www.msif.org
•nationalMSsociety.org/AssistancePrograms
For information on patient assistance programs, visit
needymeds.org.

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:
ms-coalition.org/EmergingTherapies.

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.

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

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

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?

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
http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-
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

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 http://www.huffingtonpost.com/2013/06/06/multiple-
sclerosis-treatment-immune-system-_n_3397059.html
115

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
http://ezproxy.twu.edu:2048/login?url=http://search.ebscohost.com/login.aspx?
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

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
http://library.med.utah.edu/kw/ms/path.html#6
117

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
http://www.nationalmssociety.org/about-the-society/ms-prevalence/index.aspx
19. Multiple sclerosis: answers at your fingertips (2010). Practice Nurse 39(7); 27-9.
Retrieved from http://web.ebscohost.com/ehost/detail?sid=580ab0c1-7cb3-454c-
b1faf4866de3b498%40sessionmgr4&vid=10&hid=9&bdata=JnNpdGU9ZWhvc3QtbGl
2ZSZzY29wZT1zaXRl#db=rzh&AN=2010638609
118

20. Multiple Sclerosis: Prognosis. (n.d.). Retrieved July 8, 2013, from
http://library.med.utah.edu/kw/ms/prognosis.html
21. National Multiple Sclerosis Society, General Information. (2013). The MS Disease
Modifying Medications. Retrieved from nationalMSsociety.org/DMD
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
http://www.cdc.gov/pcd/issues/2010/jan/08_0241.htm
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 http://www.overcomingmultiplesclerosis.org/About-MS/Types-of-
MS/Course-and-Prognosis/
119

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
http://ezproxy.twu.edu:2048/login?url=http://search.ebscohost.com/login.aspx?
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). http://dx.doi.org/10.4061/2010/249842
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. http://dx.doi.org/10.3121/cmr.1.1.57
120

29. Signs & Symptoms Consistent With Demyelinating Disease (n.d.). Retrieved July 6,
2013, from http://www.nationalmssociety.org/ms-clinical-care-network/clinical-
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
http://www.ncbi.nlm.nih.gov/pubmed/12591551/
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

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 aamirdash@mdanderson.org
122

Multiple sclerosis adjusted to publish

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Multiple sclerosis adjusted to publish

Similar to Multiple sclerosis adjusted to publish (20)

Recently uploaded

Recently uploaded (20)

Multiple sclerosis adjusted to publish

Editor's Notes