Multiple sclerosis
Faculty of medicine Mansoura university
Semester 4 : abilities and disabilities
PBL 15
Under supervision of : DR / AHMED JUMAH
Prepared by
Student name ID
Salman Mohamed Ali 220110080
Mostafa Mahmoud Abdelghafar 220110033
Yassin Ahmed Hammouda 220110271
Mohamed Tarek Fathi 220110090
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Acknowledgement
First of all, we are deeply grateful to Allah.
We would like to express our sincere thanks and offer our deep gratitude
to our amazing PBL tutor PROF. DR. AHMED JUMAH for his
generous help and marvelous support throughout this amazing journey. It
has been an absolute pleasure working with him.
Our deepest thanks go to Prof. DR. Ahmed Negm. Program director.
And Prof. Dr. Dalia Saleh. Head of anatomy department and our
amazing chief tutor this semester. We also want to show our respects to
Prof. Dr. Adel Bondok. Professor of anatomy and neuroscience.
Mansoura university. Egypt.
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Table of contents
NO content Page/s
1 Abstract 6
2 Introduction of MS 7
3 Aim of work of MS 8
4 Types of MS 9
5 Pathogenesis of MS 10
6 Symptoms of MS 11
7 Diagnosis and Tests for MS 12-13
8 Treatment & management of 14
MS
9 Prognosis of MS 15
10 Conclusion 16
11 References 17
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List of abbreviations
No Abbreviation Definition
1 MS Multiple sclerosis
2 CNS Central nervous system
3 BBB Blood Brain Barrier
4 MRI Magnetic resonance imaging
5 CSF Cerebero-spinal fluid
6 IFN-β Interferon beta
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List of figures
NO Figure Page NO
1 A figure of types of MS 9
A figure of immune cells and
cytokines involved in 10
2 pathogenesis of MS
3 A figure of symptoms of MS 11
4 A figure of brain MRI 12
showing multiples areas of gliosis
5 A figure of Evoked potential test 12
6 A figure of Lumbar Puncture 13
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Abstract
MS is a chronic, progressive, regenerative disorder of the CNS
characterized by disseminated demyelination of nerve fibers of the brain
and spinal cord. Although the cause of MS still unknown, the recent
documents illustrate that the cause of MS if multifactorial, including
family history, genetic predisposition combined with environmental
factors such as smoking, vit D deficiency, and infectious agents such as
EBV, the pathogenesis of MS still unclear, but it’s suspected that the
exposure of these agents produce a cascade of immune reactions leading
to demyelination of CNS nerve fibers.
There are different types of MS including: relapsing remitting (RR), the
commonest, primary progressing (PP), secondary progressive (SP),
Progressive remitting (PR). Overall, it’s important for all internist and
neurologists to be aware about this topic and the current available
information.
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Introduction
Definition :
MS is the commonest non-traumatic disabling disease to affect young adults, MS
has historically been classified as an organ-specific T-cell mediated autoimmune
disease, it is traditionally viewed as a two-stage disease, with early inflammation
responsible for relapsing–remitting disease and delayed neurodegeneration
causing non relapsing progression, i.e. secondary and primary progressive MS.
Etiology :
It is often stated that the cause of MS is unknown; however, this is not quite
correct.
EBV, smoking and vitamin D, combined with an individual’s genetic
background, play important roles in the causal pathway that results in MS
development, Migration studies consistently support MS being secondary to an
environmental exposure.
Adults migrants from low risk countries, such as the West Indies, to Europe are
at low risk of developing MS; however, children born to migrants in Europe are
at high risk.
Being truly EBV negative protects from developing MS.
The observation that organic solvents and smoked tobacco, but not oral tobacco
or snuff, are associated with MS has led to the hypothesis that these agents cause
post-translational modifications via antigen presentation occurring in the lungs
Epidemiology :
MS is increasingly a global disease, it is more common in females, but this has
not always been the case. In case series from the early 1900s the sex ratio was
almost equal. Since then, the sex ratio has steadily been increasing and it is now
close to 3:1 (F:M) in most developed countries.
increased concordance in dizygotic twins compared to siblings indicates that the
intrauterine environment is important in establishing MS risk; it is unclear
whether this is due to common environ mental exposures, or epigenetic
mechanisms, or both.
There is a genetic influence on MS susceptibility; about one in eight
patients have a family history of MS. (1)
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Aim of work
The aim of this essay is to discuss several aspects of MS with extensive focus
on the following subjects:
Pathogenesis of multiple sclerosis
Diagnosis of multiple sclerosis
Treatment and management of multiple sclerosis
Prognosis of multiple sclerosis
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Types of Multiple Sclerosis
1)Relapsing remitting MS:
The most common type, present in about 85% of patients, and RRMS onset
typically occurs in early adulthood, and, within around two decades,
approximately half will go on to develop secondary progressive MS (SPMS).
2) Secondary progressive MS:
It starts as RRMS followed by progression and deterioration in signs and
symptoms.
3) Primary progressive MS:
It affects about 15% from the patients and characterized by rapid progression.
4) Progressive Remitting MS:
The most serious type of MS, it’s characterized by rapid progression with
intermittent relapsing episodes. (2)
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Pathogenesis of MS
Pathogenesis of multiple sclerosis :
1 ) Systemic immune related events :
Macrophages expose myelin to T lymphocytes.
Myelin antigens activate T & B lymphocytes in peripheral lymphoid tissues.
Activated T cells proliferate and differentiate into CD4, CD8 cytotoxic T cells.
2 ) Blood brain barrier related events :
Leucocyte migration through BBB endothelial cells via adhesion molecules.
Then T cells enter the perivascular space through BBB, there is matrix
metalloproteinase which degrade the extracellular matrix of BBB, facilitate this
migration.
3 ) Central nervous system related events :
Within CNS parenchyma, once T cells encounter the specific autoantigen again and
in consequence get reactivated and amplify immune response recruiting
immunocompetent cells. So demyelination is caused by these activated
macrophages. In addition, inflammation is augmented by releasing cytokines,
chemokines reactivated oxygen species including nitric oxide >> all of these make
more destruction Inflammation process may end in sclerosis. (3)
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Symptoms of MS
MS can cause a wide range of symptoms that are often unpredictable. They vary
heavily from person to person and may appear in different combinations
depending on the area of the nervous system affected. Some people's symptoms
develop and worsen steadily over time, while for others they come and go. (4)
Some of the most common symptoms of MS include:
• Fatigue
• Vision problems due to swelling of the optic nerve (optic neuritis)
1. Temporary loss of vision
2. Double Vision
3. Blurry Vision
• Abnormal sensations such as numbness and tingling
• Muscle spasm, stiffness and weakness
• Mobility problems
1. Lack of coordination
2. Clumsiness
3. Dizziness
4. Shaking of the limbs (vertigo)
• Sexual problems
• Cognitive problems with
1. Thinking
2. Memory
3. Concentration
4. Judgement
5. Attention
• Mood disturbance
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Diagnosis and Tests For MS
Diagnosing MS is complicated because no single test can positively
diagnose it. It relies on ruling out other possible conditions that might
produce similar signs and symptoms. To confirm a diagnosis, there has to
be evidence of at least 2 separate attacks of multiple sclerosis-like
symptoms.
During examination, a neurologist asks about the patient’s medical
history and his current symptoms. A neurological examination is also
performed where the neurologist will look for abnormalities, changes or
weaknesses in vision, eye movement, hand or leg strength, balance and
coordination, speech and reflexes. All this gives neurologist a better
picture of where in the brain or spinal cord the problem is. It can also
identify something else behind patient symptoms that's not MS. (5)
While the neurologist may strongly suspect MS at this stage, they won't be able
to give a diagnosis until other test results confirm that it's MS. These tests
include:
1 ) MRI scan : An MRI scanner uses a strong magnetic field to create a detailed
image of inside the brain and spinal cord. It's very accurate and can pinpoint the
exact location and size of any inflammation, damage or scarring (lesions).
MRI scans confirm a diagnosis in over 90 per cent of people with MS. (6)
2 ) Evoked potential tests : These tests measure the time it takes for the brain to
receive messages or signals from the eyes, ears and skin. Signals to and from the
brain will be slower if MS has damaged the myelin covering around some of
nerves. (7)
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3 ) Lumbar puncture : For this test the medical staff give the patient a local
anesthetic, then put a needle in his lower back. It goes into the space around the
spinal cord and collects a small sample of CSF. This is then tested for signs of
MS. People with MS nearly always have antibodies in this fluid. Antibodies are a
sign that the immune system has been active in the brain and spinal cord. People
who don't have MS don't normally have antibodies in this fluid. (8)
4 ) Blood tests : A neurologist might also want to rule out conditions that are
similar to MS by running some other tests. These could include blood tests
to check for particular antibodies, and inner ear tests to check for balance.
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Treatment & management of MS
There is no cure for multiple sclerosis so the goals of MS treatment are to :
1 ) Treatments for MS attacks :
Corticosteroids, such as oral prednisone and intravenous
methylprednisolone, are prescribed to reduce nerve inflammation.
Side effects : may include insomnia, increased blood pressure, increased
blood glucose levels, mood swings and fluid retention.
2 ) Treatments to modify progression :
IFN-β medications. These drugs used to be the most prescribed medications
to treat MS. They work by interfering with diseases that attack the body and
may decrease inflammation and increase nerve growth. They are injected
under the skin or into muscle.
Side effects : may include flu-like symptoms and injection-site reactions.
You'll need blood tests to monitor your liver enzymes because liver damage is
a possible side effect of interferon use.
3 ) Treatments for MS signs and symptoms :
A physical therapist can teach patient stretching and strengthening exercises and
show how to use devices to make it easier to perform daily tasks.
Other Medications also may be prescribed for depression, pain, sexual
dysfunction, fatigue, insomnia, and bladder or bowel control problems that are
associated with MS. (9)
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Prognosis of MS
The prognosis with MS depends on the type of MS diagnosed with, of
which there are four main types. These include relapsing remitting MS
(RRMS), Progressive-Relapsing MS (PRMS), primary-progressive
MS (PPMS), and secondary-progressive MS (SPMS).
The average longevity in the population of patients with MS is very difficult to
estimate because it varies widely from patient to patient. Average life span of 25
to 35 years after the diagnosis of MS is made are often stated. Some of the most
common causes of death in MS patients are secondary complications resulting
from immobility, chronic urinary tract infections, difficulty in swallowing and
breathing. Some of the complications in this category are chronic bed sores,
urogenital sepsis, and aspiration or bacterial pneumonia so majority of people
with MS pass away from other things.
Factors that are associated with a relatively better disease course are:
1) being female
2) being less than 40 years old when diagnosed
3) having few relapses in the first few years after diagnosis
4) making a complete recovery from relapses
5) having long intervals between relapses
6) having symptoms that are mainly sensory
What can I do to improve my prognosis?
Many people diagnosed with MS take steps to improve their general health, such
as altering their diet or taking more exercise. There is no direct evidence to
link dietary interventions or supplements to improved prognosis in MS.
However, it is possible to reduce your risk of co-morbidities through healthy
living. (10)
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Conclusion
MS is the commonest non-traumatic disabling disease nowadays, with no
specific known cause, although, genetic predisposition and environmental
factors can be suspected, MS can affect eye, equilibrium, motor and sensory
functions. MRI, evoked potential, lumbar puncture and blood test can be
used for diagnosis. Till now, there’s no specific treatment, anti-inflammatory
drugs and palliative treatment can be used for management of the case.
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References
(1) Dobson, Ruth, and Gavin Giovannoni. "Multiple sclerosis–a review." European
journal of neurology 26.1 (2019): 27-40.
(2) McKay, Kyla A., et al. "Risk factors associated with the onset of relapsing-remitting
and primary progressive multiple sclerosis: a systematic review." BioMed research
international 2015 (2015).
(3) Prat, Alexandrea; Antel, Jackb. Pathogenesis of multiple sclerosis. Current Opinion in
Neurology 18(3):p 225-230, June 2005. | DOI: 10.1097/01.wco.0000169737.99040.31
(4) Gelfand JM. Multiple sclerosis: diagnosis, differential diagnosis, and clinical
presentation. Handb Clin Neurol. 2014;122:269–290.
(5) Cohen JA, Rae-Grant A. Diagnosing multiple sclerosis.In: Handbook of Multiple
Sclerosis. 2nd ed. London, England:Springer Healthcare; 2012:15-27.
(6) Zivadinov R. Role of neuroimaging in multiple sclerosis.In: Minagar A, ed. Multiple
Sclerosis: A Mechanistic View.Amsterdam, the Netherlands: Elsevier B.V.; 2016:443-
478.
(7) Cohen JA, Rae-Grant A. Clinical features. In: Handbook of Multiple Sclerosis. 2nd
ed. London, England: Springer Healthcare; 2012:7-13.
(8) Giovannoni G. Cerebrospinal fluid analysis. In: Goodin DS, ed.Handbook of Clinical
Neurology: Multiple Sclerosis and Related Disorders. 3rd series. Amsterdam, the
Netherlands: Elsevier B.V.;2014:681-701.
(9) Mayo Clinic. (2022, December 24). Multiple Sclerosis. Mayo Clinic.
https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/diagnosis-
treatment/drc-20350274
(10) Prognosis. (n.d.). MS Trust. https://mstrust.org.uk/a-z/prognosis
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