Introduction about Multiple Sclerosis. Risk factors affect to Multiple Sclerosis. When to Suspect Multiple Sclerosis. Evaluation and Diagnosis of Multiple Sclerosis. How to treatment of Multiple Sclerosis. Treatment of Multiple Sclerosis with Monoclonal Antibody.

1. Multiple Sclerosis

2. 1. INTRODUCTION
2. RISK FACTORS OF MULTIPLE SCLEROSIS
3. WHEN TO SUSPECT MS
4. EVALUATION
5. DIAGNOSIS
6. TREATMENT
PARTS

3. INTRODUCTION
• Multiple sclerosis (MS) is the most common
immune-mediated inflammatory demyelinating
disease of the central nervous system.
• Characterized by multifocal areas of
demyelination with loss of oligodendrocytes and
astroglial scarring. Axonal injury is also a
prominent pathologic feature, especially in the
later stages.
• Certain clinical features are typical of MS, but the
disease has a highly variable pace and many
atypical forms.
• Multiple sclerosis is a disease that causes vision
problems, numbness and tingling, muscle
weakness, and other problems.

4. In multiple sclerosis, the immune system attacks
nerve cells in the brain and spinal cord. These
nerve cells work kind of like electrical wires. They
carry electrical signals and are wrapped in
insulation that helps the electrical signal move
quickly down the nerve. This "insulation" is made
of a material called myelin. Multiple sclerosis
damages this myelin, so the nerve cells
cannot carry signals very well.

5. Risk factors of Multiple Sclerosis
These factors may increase your risk of developing multiple sclerosis:
• Age. MS can occur at any age, but usually affects people somewhere
between the ages of 16 and 55.
• Sex. Women are more than two to three times as likely as men are to
have relapsing-remitting MS.
• Family history.
• Certain infections. A variety of viruses have been linked to MS,
including Epstein-Barr.
• Race. White people, particularly those of Northern European descent,
are at highest risk of developing MS. People of Asian, African or Native
American descent have the lowest risk.

6. • Climate. MS is far more common in countries with temperate
climates, including Canada, the northern United States, New Zealand,
southeastern Australia and Europe.
• Vitamin D. Having low levels of vitamin D and low exposure to
sunlight is associated with a greater risk of MS.
• Certain autoimmune diseases. You have a slightly higher risk of
developing MS if you have thyroid disease, type 1 diabetes or
inflammatory bowel disease.
• Smoking. Smokers who experience an initial event of symptoms that
may signal MS are more likely than nonsmokers to develop a second
event that confirms relapsing-remitting MS.
Risk factors of Multiple Sclerosis

7. What are the symptoms of MS?
• Numbness, tingling, and feeling "pins and needles"
• Muscle weakness or spasms, which can cause you to drop things or
fall
• Vision problems, eye pain, and odd eye movements
• Feeling dizzy or off-balance, which can cause you to fall
• Trouble walking or speaking
• Problems controlling your bowels or bladder
• Sensitivity to heat, which makes symptoms worse
• Trouble thinking clearly

8. Common manifestations of MS
Symptoms and signs Total (percent)
Sensory in limbs 31
Visual loss 16
Motor (subacute) 9
Diplopia 7
Gait disturbance 5
Motor (acute) 4
Balance problems 3
Sensory in face 3
Lhermitte sign (electric shock-like sensations that run down the back and/or limbs upon flexion of the
neck)
2
Vertigo 2
Bladder problems 1
Limb ataxia 1
Acute transverse myelopathy 1
Pain <1
Other 3
Polysymptomatic onset

9. WHEN TO SUSPECT MS
• The clinical presentation is suggestive of focal or multifocal
demyelination involving the central nervous system.
• The typical patient presents as a young adult with one or more
clinically distinct episodes of central nervous system dysfunction
followed by at least partial resolution. Symptoms usually develop over
hours to days and then gradually remit over weeks to months, though
remission may be incomplete. Presenting symptoms and signs may be
either monofocal (consistent with a single lesion) or multifocal
(consistent with more than one lesion).

10. WHEN TO SUSPECT MS
• While there are no clinical findings that are unique
to MS, some are highly characteristic.
• Lhermitte's sign is a short, intense sensation
that feels similar to an electric shock passing down
the neck and spine and radiating through the trunk
and limbs.
• Clinically, internuclear ophthalmoplegia (INO) is a
horizontal gaze palsy; it results from a brainstem
lesion affecting the MLF between the nuclei of CN
VI and III, most commonly in the pons.
Features suggestive of multiple sclerosis
Relapses and remissions
Onset between ages 15 and 50 years
Optic neuritis
Lhermitte sign
Internuclear ophthalmoplegia
Fatigue
Heat sensitivity (Uhthoff phenomenon)
Features atypical for multiple sclerosis
Steady progression
Onset before age 10 or after age 50 years
Cortical deficits such as aphasia, apraxia, alexia, or neglect
Rigidity or sustained dystonia
Convulsions
Early dementia
Deficit developing within minutes

11. • Lesion of the medial longitudinal
fasciculus (MLF) resulting in
internuclear ophthalmoplegia
(INO).
Internuclear ophthalmoplegia ?

12. Are there different forms of MS?
Relapsing-remitting – This means the symptoms of MS come and go. When
the symptoms flare up, it is called an "attack" or "relapse." These attacks can
last for days to weeks and usually get better slowly. In between attacks, people
often feel pretty normal. But some people have problems that last even after
an attack gets better. Relapsing-remitting is the most common type of MS.
Secondary progressive – This means the symptoms come and go at first but
then begin to steadily get worse. This happens to many people who start out
with relapsing-remitting disease.
Primary progressive – This means the symptoms steadily get worse from the
beginning.

13. EVALUATION
• Typical presentation, insufficient clinical and MRI evidence to confirm
the diagnosis of MS by the McDonald criteria:
1. Lumbar puncture
2. Visual evoked potentials
3. And/or optical coherence tomography
• Atypical history, examination, or MRI:
1. Spine MRI
2. Lumbar puncture
3. And/or autoantibody determination for aquaporin-4 (AQP4)
and myelin-oligodendrocyte glycoprotein (MOG) antibodies

14. Lumbar puncture
• An oligoclonal band is a protein called an
immunoglobulin. The CSF oligoclonal
band screen looks for these bands in your
CSF. Their presence suggests inflammation of
the central nervous system due to infection or
another disease.
• Oligoclonal bands are found in up to 95
percent of patients with clinically definite MS
Qualitative assessment of CSF for oligoclonal IgG bands using isoelectric focusing
– accompanied by a concomitant analysis of the serum – is the most important
CSF study when determining a diagnosis of MS.

15. MAGNETIC RESONANCE IMAGING
• Sensitivity and specificity of up to 87 and 73 percent
• MRI detects many more MS lesions than computed tomography
(CT), and it is able to detect MS demyelinating plaques in
regions that are rarely abnormal on CT such as the brainstem,
cerebellum, and spinal cord .
Black holes Dawson fingers

16. Black holes
Axial T1-weighted images (A and B) demonstrate multiple
hypointense areas (black holes) in a patient with
longstanding MS.
MAGNETIC RESONANCE IMAGING

17. Dawson fingers
Axial (A) and sagittal (B) MRI FLAIR images of the brain
demonstrate multiple, ovoid periventricular lesions
(Dawson fingers) in a patient with multiple sclerosis.
MAGNETIC RESONANCE IMAGING

18. T2-weighted sagittal (A) and axial (B) images
show a focus of hyperintensity in the posterior
columns of the cervical spinal cord at the C2
level. Post-gadolinium T1-weighted sagittal (C)
and axial (D) images demonstrate enhancement
consistent with an active plaque.
Axial FLAIR (A) image demonstrate a large demyelinating
lesion in the left pons. The lesion shows peripheral
enhancement on axial post-contrast T1-weighted image
(B).
MAGNETIC RESONANCE IMAGING

19. Optical coherence tomography (OCT)

20. DIAGNOSIS: McDonald Critieria
Number of lesions with
objective clinical
evidence
Additional data needed for a diagnosis of multiple
sclerosis
≥2 clinical attacks ≥2 None*
1 Dissemination in space demonstrated by an additional clinical
attack implicating a different CNS site or by MRI criteria for
dissemination in space Δ
1 clinical attack ≥2 Dissemination in time demonstrated by an additional clinical
attack or by MRI criteria for dissemination in time◊ OR
demonstration of CSF-specific oligoclonal bands§
1 Dissemination in space demonstrated by an additional clinical
attack implicating a different CNS site or by MRI criteria for
dissemination in spaceΔ
AND
Dissemination in time demonstrated by an additional clinical
attack or by MRI criteria for dissemination in time◊ OR
demonstration of CSF-specific oligoclonal bands§
§ The presence of CSF-specific oligoclonal bands does not demonstrate dissemination in time per se but can substitute for the requirement for demonstration of this measure.

21. What defines an attack?
An MS attack is defined by the McDonald criteria as a monophasic
clinical episode with patient-reported symptoms and objective findings
typical of MS, reflecting a focal or multifocal inflammatory demyelinating
event in the central nervous system, developing acutely or subacutely,
with a duration of at least 24 hours, with or without recovery, and in
the absence of fever or infection. Attack, relapse, exacerbation, and
(when it is the first episode) clinically isolated syndrome (CIS) are
synonyms. The most common initial attacks are sensory disturbances,
motor weakness, and visual complaints (either monocular visual loss or
diplopia).

22. What is objective clinical evidence?
The MS attack should be confirmed by objective clinical evidence, that
is, an abnormality on neurologic examination, imaging (eg, MRI or
optical coherence tomography), or neurophysiologic testing (eg,
visual evoked potentials) that corresponds to the anatomic location
suggested by the symptoms of the current or historical attack.

23. Treatment
Acute exacerbations of multiple sclerosis
1. GLUCOCORTICOIDS
Three to seven day courses of intravenous methylprednisolone, 500 to
1000 mg daily
An alternative is a three to seven day course of oral prednisone, 625 to
1250 mg daily
The bioavailability of oral prednisone (1250 mg) appears to be equal to that of
intravenous methylprednisolone (1000 mg). However, one study found a higher peak concentration
after a single dose of intravenous methylprednisolone than after a single dose of the oral formulation
PLASMA EXCHANGEGLUCOCORTICOIDS
2. PLASMA EXCHANGE may be beneficial in patients with
acute central nervous system (CNS) inflammatory demyelinating
disease who do not respond to glucocorticoid therapy.

24. Treatment
Treatment of progressive multiple sclerosis
Treatment directed at the progressive phase of MS is typically more difficult
than treatment of relapsing forms of MS
1. Primary progressive 2. Secondary progressive
Primary progressive MS is characterized
by progressive accumulation of
disability from disease onset with
occasional plateaus, temporary minor
improvements, or acute relapses still
consistent with the definition.
Secondary progressive MS is characterized by
an initial relapsing-remitting MS disease
course followed by gradual worsening with or
without occasional relapses, minor remissions,
and plateaus.

25. Primary progressive — For patients with PPMS, suggest treatment
with ocrelizumab, the only drug to receive regulatory approval for use in adult
patients with PPMS. The approval was based on the results of the ORATORIO
trial, which showed that ocrelizumab reduced the risk of disability progression
among patients with PPMS.
All other treatments that are sometimes used for PPMS are empiric, as they
lack convincing clinical trial evidence of effectiveness:
Intravenous glucocorticoid monthly pulses (typically 1000 mg
of methylprednisolone).
Methotrexate, oral or subcutaneous, 7.5 to 20 mg per week
Cladribine intravenous or subcutaneous – Cladribine has not been studied in
large trials for PPMS, although some data suggest benefit for patients with
SPMS
Intravenous immune globulin (IVIG).

26. Secondary progressive — For patients with relapsing-remitting MS (RRMS) who
reach the stage of SPMS, particularly those with evidence of active disease by
clinical or MRI measures, immune-modulating treatment options include:
Siponimod monotherapy – Evidence from a placebo-controlled randomized trial
suggests that oral siponimod was effective for reducing disability progression at three and
six months for patients with SPMS.
Cladribine monotherapy – Cladribine is an option for patient with active SPMS (ie,
patients with SPMS who are still experiencing relapses), but is generally reserved for
patients who do not tolerate or have inadequate response to other disease-modifying
therapies for MS.
Treatment of Multiple Sclerosis With Monoclonal Antibody. Refer to:
https://booksdoctor.blogspot.com/2019/07/treating-multiple-sclerosis-with-monoclonal-antibodies.html for
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