multiple sclerosis

1. Multiple Sclerosis
Name : Vihari Vichakshana Rajaguru
Group No : 32
4th year 1st semester (2016)
Kursk State Medical University

2. Introduction
 Transmission of action potentials along myelinated
axons.
 An action potential “jumps” from node to node.
 Voltage-gated Na+ channels are present only at the
nodes of Ranvier.

3. What is MS ?
 a chronic, typically progressive disease
involving damage to the sheaths of nerve
cells in the brain and spinal cord.
 The immune system attacks the protective
sheath (myelin) that covers nerve fibers
and causes communication problems
between your brain and the rest of your
body. Eventually, the disease can cause
the nerves themselves to deteriorate or
become permanently damaged

4. No 01
No 02
No 03

5. Global distribution of MS

6. Etiology
 Cause of MS is still not known,
scientists believe that the interaction
of several different factors may be
involved.
 Immunologic Factors
 Environmental Factors
 Infectious Factors
 Genetic Factors

7. Path physiology
Blood-brain barrier
breakdown
The BBB prevent entrance of T cells into the nervous system.
The blood–brain barrier is normally not permeable to these types of
cells, unless triggered by infection or a virus, which decreases the
integrity of the tight junctions.
When the blood–brain barrier regains its integrity, usually after
infection or virus has cleared, the T cells are trapped inside the
brain.
Autoimmunology The immune system attacks the nervous system, forming plaques
or lesions.
Commonly involves white matter.
Destroys oligodendrocytes- causing demyelination
Remyelination occurs in early phase but not completely.
Repeated attacks lead to fewer remyelination.
Inflammation T-cells attacks on myelin triggers inflammatory processes,
stimulating other immune cells and soluble factors like cytokines
and antibodies.
Leaks form in the BBB cause swelling, activation of macrophages,
and more activation of cytokines and other destructive proteins

12. CLASSIFICATION OF MULTIPLE SCLEROS
PRMS Progressive Relapsing MS
SPMS Secondary Progressive MS
PPMS Primary Progressive MS
RRMS Relapsing/ Remitting MS
Gradual progression of the disease from its
onset with no relapses or remissions
Unpredictable attacks which may or may not leave
permanent deficits followed by periods of remission
Initial RRMS that suddenly begins to decline without
periods of remission and relapses.
Steady decline since onset with super-imposed
attacks.

13.  Progressive Relapsing
Mild infrequent sensory exacerbations
with full recovery.
 Secondary Progressive
Condition of patients with
relapsing/remitting disease begins to
gradually worsen over time with
resulting accumulation of neurological
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.

14.  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.
 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.

15. The most common
initial symptoms
• changes in sensation
in the arms, legs or
face : numbness
(33%)
• Optic neuritis (20%)
• weakness (13%)
• double vision-
internuclear
opthalmoplegia (7%)
• unsteadiness when
walking (5%)
• and balance

16. sensory exam
◦ - ascending numbness starting in the
feet;
◦ - bilateral hand numbness;
◦ - hemiparesthesia;
◦ - dysesthesia in one of the above
distributions;
◦ - generalized heat intolerance
 Objectively the most common sensory
findings in the"numb" areas are dorsal
column signs, such as reduction of
vibration, proprioception and stereognosis,
rather than problems with spinothalamic
tract.

17. Right internuclear
ophthalmoplegia in a
patient with multiple
sclerosis. In the initial
phase of leftward gaze
(upper photograph), only
the left eye is abducted.
The right eye follows,
after a delay (lower
photograph).

18. Lhermitte's
sign (25-40%)
is an electrical
sensation that
runs down the
back and into the
limbs and is
produced by
bending the neck
forwards. The
sign suggests a
lesion of the
dorsal columns of
the cervical cord
or of the caudal
Uhthoff's
phenomenon
is the worsening of
neurologic
symptoms in
multiple sclerosis
and other
neurological,
demyelinating
conditions when the
body gets
overheated from
hot weather,

19. Ongoing Symptoms and
Signs
 Motor system:
◦ -weakness (variable severity mono-
and paraparesis, hemiparesis,
quadriparesis)
◦ -increased spasticity resulting in
spastic gait
◦ -pathologic signs (Babinski's,
Chaddock's, Hoffmann, Oppenheim's,
etc.) -dysarthria
 Cerebellar signs:
◦ -incoordination (dysdiadochokinesia,
problems with heel-to-shin test)
◦ -slowing of rapid repeating movements
◦ -cerebellar ataxia (ataxic gait)
◦ -scanning speech

20. INVESTIGATION
CSF oligoclonal bands, abnormal colloidal gold curve, elevated γ-
globulin IgG, mild mononuclear pleocytosis (<40 cells/mL),
myelin debris, normal or slightly elevated protein. (Myelin basic
Protein)
Blood
test
•B-12 and folate levels or antinuclear antibody (ANA) titers.
•Antiphospholipid antibody syndrome must be undertaken in
patients with evidence of blood dyscrasia and in women with
unexplained miscarriages or history of deep venous thrombosis.
•elevated erythrocyte sedimentation rate (ESR) and positive
titers of rheumatoid factor (RF) should help identify the presence
of a vasculitic disorder that may be mimicking MS.
MRI MRI of the head and spine (more sensitive than CT): May show
many plaques.
MRI reveals multiple lesions with high T2 signal intensity and
one large white matter lesion. These demyelinating lesions may
sometimes mimic brain tumors because of the associated
edema and inflammation.

25. Diagnostic Criteria
Clinical Presentation Additional Data Needed
* 2 or more attacks (relapses)
* 2 or more objective clinical
lesions
None; clinical evidence will
suffice (additional evidence
desirable but must be consistent
with MS)
* 2 or more attacks
* 1 objective clinical lesion
Dissemination in space,
demonstrated by:
* MRI
* or a positive (cerebrospinal
fluid) CSF and 2 or more MRI
lesions consistent with MS
* or further clinical attack
involving different site
Diagnosis is based on McDonald’s Criteria (Revised
2010)

26. * 1 attack
* 2 or more objective clinical lesions
Dissemination in time, demonstrated
by:
* MRI
* or second clinical attack
* 1 attack
* 1 objective clinical lesion
(monosymptomatic presentation)
Dissemination in space demonstrated
by:
* MRI
* or positive CSF and 2 or more MRI
lesions consistent with MS
and
Dissemination in time demonstrated
by:
* MRI
* or second clinical attack
Insidious neurological progression
suggestive of MS
(primary progressive MS)
One year of disease progression
(retrospectively or prospectively
determined) andTwo of the following:
a. Positive brain MRI (nine T2 lesions
or four or more T2 lesions with
positive VEP)b. Positive spinal cord
MRI (two focal T2 lesions)c. Positive
CSF

27. Treatment
 As of 2011, six treatments have been approved by
FDA
1. Interferon beta
1a (Avonex, CinnoVex,ReciGen and Rebif)
2. Interferon beta-1b (Betaseron )
3. Glatiramer acetate (Copaxone), a non-
steroidalimmunomodulator.
4. Mitoxantrone, is an immunosuppressant
5. Natalizumab (Tysabri)
Steroids: methylprednisolone (MP) 500–1,000 mg/d IV for 5
days
followed by tapered oral prednisone or MP 1 g/d IV for 3 days
± oral taper

28. MANAGEMENT
Spasticity Baclofen 5 mg PO 1–3 t.i.d. and increase as needed
Diazepam 2–5 mg PO at bedtime
Pain NSAIDs
Gabapentin effective vs. MS pain syndromes at 300 mg/d PO, may increase to
1,800 mg/d within 1 week, max dose 3,600 mg/d
Bladder
dysfunction
Propantheline 7.5 mg PO q3–4h to start, increase to 15 mg t.i.d. to q.i.d. plus
15–30 mg at bedtime
Oxybutynin chloride 5 mg PO t.i.d.–q.i.d.
Prophylactic antibiotics for urinary infections
Self-catheterizations for inadequate bladder emptying
Constipation: Stool softeners, bulk-producing agents, laxative suppositories
Incoordination or
tremors:
Incoordination or tremors:
Depression and
emotional lability
Antidepressant agents such as SSRIs.
Psychotherapy and support
Paranoia or
mania
Haloperidol lithium or atypical antipsychotic
Hemifacial and
dysesthesias
Carbamazepine 100–200 mg PO once or twice a day to start; increase to total
daily dosage of 600–1,600 mg t.i.d.–q.i.d.
Must monitor serum levels

29. Other regime
 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

30.  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.

31. Prognostic Factors in Patients with
Multiple Sclerosis
Good prognosis
 Optic Neuritis
 Isolated sensory
symptoms
 Long interval to
second relapse
 No evidence of
disability after 5
years
 Female gender
Poor Prognosis
 ‘Multifocal’ Clinically
Isolated Syndrome
 Efferent
(motor/cerebellar)
systems
 High relapse rate in 5
years
 Substantial disability
after 5 years
 Abnormal MRI with

32. 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
 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