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MULTIPLE SCLEROSIS
Dr. ANIL DHAKAL
MD (INTERNAL MEDICINE)
 MYELIN SHEATH
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 Oligodendrocytes in
CNS
 Schwann cells in PNS
 MULTIPLE SCLEROSIS-
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Introduction
 Multiple sclerosis is a disease of white matter
& affects the myelin sheath
 Multiple sclerosis belongs to group/class of

disease
 Autoimmune (target myelin producing cells)
 Inflammatory
 Demyelinating
 MULTIPLE SCLEROSIS-
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Introduction
 Cell-mediated autoimmune condition characterized by
repeated episodes of inflammation of the nervous tissue
with loss of the insulating myelin sheath in different parts
of CNS (brain and spinal cord).
 MULTIPLE SCLEROSIS-
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Introduction
 Hall mark of disease is – lesions are spread over
TIME & SPACE
 Symptoms are recurrent
 Symptoms are due to involvement of different parts of
CNS simultaneously
 ETIOLOGY
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 Interplay between environmental and genetic

factors. Highest incidence in caucasians.
ENVIRONMENTAL FACTORS GENETIC FACTORS
Sunlight exposure & vitamin D Significant risk of familial
(protects) recurrence
Highest risk in first-degree relatives

Exposure to Epstein-Barr virus Monozygotic twins have a high

(EBV) concordance

Inheritance appears to be polygenic

 PATHOGENESIS
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 Starts with the entry of activated T

lymphocytes across the blood-brain barrier

 Causing destruction of the oligodendrocyte (in

CNS)

 Resulting in demyelination
 PATHOGENESIS
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 Later PLAQUE formation takes place
1. Lymphocytes and macrophages infiltration
2. Circumscribed area of disintegrated myelin sheath
3. Gliosis (scar formation) latter in course of disease
 Typical site of lesions
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 Heavily myelinated areas

 Periventricular area
 Juxtacortical area
 Infratentorial area
 Spinal cord
 CLINICAL PRESENTATION
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 Around 80% of patients have a relapsing and

remitting clinical course of episodic
dysfunction of the CNS with variable recovery
 CLINICAL PRESENTATION
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 Secondary progressive MS: follows on relapsing-

remitting MS.
 Symptoms become more/worsen with fewer
remissions
 CLINICAL PRESENTATION
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 About 50% of those with relapsing-remitting MS

develop secondary progressive MS during the first
ten years
 CLINICAL PRESENTATION
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 Primary progressive MS: from the beginning,

symptoms gradually develop and worsen over time
(10-15%)
 No relapse & remission
Correlation between symptoms & pathology
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 Initial disruption in nerve transmission is due to the

effect of inflammatory cytokines
 Reversible
 Explains the rapid recovery of some deficits and
benefit from corticosteroids .
 Structural disruption of the myelin is later event
 In established MS there is progressive axonal

loss due to direct damage

 Cause of progressive and persistent disability latter
 SIGNS AND SYMPTOMS
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 SIGNS AND SYMPTOMS
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 Wide range
 The most common features are

VISUAL
1. Optic neuritis
 Very common, usually due to demyelination of the

optic nerve
 Causes acute & painful, reduction or loss of vision in
one eye resulting in blindness or hemianopia
 SIGNS AND SYMPTOMS
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2.Diplopia
 6th cranial nerve palsy

 Internuclear ophthalmoplegia

 Cause problems of eye movement resulting

in diplopia and nystagmus
 SIGNS AND SYMPTOMS
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3. Internuclear
ophthalmoplegia
 Due to dysfunction in

the medial longitudinal
fasciculus (MLF)
 Tract that allows conjugate
eye movement by connecting
abducens nucleus of the
contralateral side to the
oculomotor nucleus of the
ipsilateral side
 SIGNS AND SYMPTOMS
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 Facial palsy
 Bell's palsy can occur alone or with
other indications of brainstem disorder
(Millard Gubler syndrome
 Trigeminal nerve involvement
 Trigeminal neuralgia (Tic doloreaux) – most
common
 SIGNS AND SYMPTOMS
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 Hearing and balance

 8th cranial nerve involvement
Deafness and feelings of unsteadiness
 Brainstem involvement
Vomiting
Ataxia
Severe vertigo
 SIGNS AND SYMPTOMS
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 Cognitive symptoms (thinking, reasoning,

or remembering)
 Visual and auditory attention may be
affected.
 Can affect intelligence with loss of
memory.
 SIGNS AND SYMPTOMS
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 Sensory symptoms
 Posterior column involvement – tightness or
burning sensations
 Lhermitt’s sign (+)
 Spinothalamic tract involvement - loss of
thermal and pain sensation
 Spinal nerves involvement - Loss of
sensation in the legs.
 SIGNS AND SYMPTOMS
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 Spinal cord
 Transverse myelitis
 Brown-Séquard syndrome
 SIGNS AND SYMPTOMS
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 Autonomic system
 Bladder symptoms
Urgency and frequency with incontinence

 Impaired rectal sphincter

Faecal incontinence

 Sexual problems
Impotence common in men

 Loss of thermoregulation
Excess sweating, pyrexia or hypothermia
 Differential diagnosis(of first attack)
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 Vitamin B12 deficiency

 Spinal cord compression
 Cerebral variant of systemic lupus erythematosus
(SLE) 
 Sarcoidosis
 In patients of African or Asian origin –
 AIDs
 Tropical spastic paraplegia
 Neuromyelitis optica
 DIAGNOSIS
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The hall mark of diagnosis of MS is

 Dissemination in space
 Two or more different regions of the central
white matter have been affected
 Dissemination in time
 Have been affected at different times
DIAGNOSTIC CRITERIA: Macdonald 2017
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DIAGNOSTIC CRITERIA: Macdonald 2017
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 DIAGNOSIS
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 Diagnosis is easy when patient presents with

relapsing & remitting variety
 Can be diagnosed on clinical grounds +

imaging
 DIAGNOSIS
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• Problem arises when patient presents

with
• A single lesion
• First episode
 DIAGNOSIS
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 To fulfill the criterion of dissemination in space in

a patient with only one lesion

 Repeat imaging in a few months

 Should demonstrate at least one lesion in at least

two of four typical sites

 Periventricular
 Juxtacortical
 Infratentorial
 Spinal cord
 INVESTIGATIONS
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 Identify multiple sites of

neurological involvement

 Imaging (MRI)
Will show plaques

 Visual evoked potentials

 INVESTIGATIONS
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VISUAL EVOKED POTENTIALS

 Electrical potentials, initiated by brief visual
stimuli, which are recorded from the scalp
overlying visual cortex
 Visual evoked potential can detect clinically silent
lesions in up to 70% of patients in MS
 INVESTIGATIONS
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 Demonstrate inflammatory nature of

lesion(s)
 CSF examination
Cell count
 Lymphocytic pleocytosis in the acute phase
Protein electrophoresis (oligoclonal bands)
 INVESTIGATIONS
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 Exclude other conditions

 Chest X-ray
 Serum angiotensin-converting enzyme
(ACE) for sarcoidosis
 Serum B12
 For SLE
 Antinuclearantibodies
 Antiphospholipid antibodies
 MRI in MS
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 Revolutionizing the investigation,

diagnosis, and even the treatment of MS
 Only imaging modality needed

 Far surpasses all other tests with respect to

its positive predictive value
 MRI is the most sensitive technique
 For imaging lesions in both brain and spinal cord
 In excluding other causes of the neurological deficit
 MRI in MS
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 Can show the plaques &

 Dissemination in 'space‘
 Multiple lesions in several different sites
 Dissemination in 'time‘
 Serial MRI scans show new lesion developing at least
3 months after the initial presentation
 MANAGEMENT
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Involves treatment of
 Acute episode

 Prevention of future relapses

 Treatment of complications

 Management of the patient's disability

 MANAGEMENT: Acute episode
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 Pulses of high-dose methylprednisolone to

shorten the duration of the episode
 Intravenously (1g daily for 3 days)
or
 Orally (500 mg daily for 5 days)
 Followedby oral prednisone at 60–80 mg daily for 1
week with a taper over the ensuing 2–3 weeks
 Gastric protection should be provided by
ranitidine 150 mg bd, or omeprazole 20 mg
daily
 MANAGEMENT
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 Prolonged administration of steroids does not alter

the long-term outcome and should be avoided
 Pulses of steroids can be given up to three times in
a year to those having significant disability
 Osteoporosis prophylaxis to be considered
 MANAGEMENT
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 In patients with severe relapses &

unresponsive to medication may respond
to
 Plasmapheresis
 IVIG (Intravenous immunoglobulin)
 They bring about Immune modulation
 Disease-modifying therapy for prevention of relapse
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 Interferon beta
 Balances the expression of pro- & anti-
inflammatory agents in the brain
 Reduces number of inflammatory cells
crossing blood brain barrier
 Widely used
 Reduces the number of relapses by some 30%
 Given IM or SC 3 times a week
 Disease modifying therapies
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 For relapsing forms of MS (RMS, SPMS with

exacerbations)
 Anti CD20 mab (highly effective)
 Ocrelizumab
 Ofatumumab
 Rituximab
 Natalizumab
 Disease modifying therapies..contd
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 SIP receptor modulators (moderately effective) :

Sphingosin-1- phosphate
 Fingolimod
 Ozanimod
 Ponesimod
 Disease modifying therapies..contd
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 Dimethyl fumarate (moderately effective)

 Glatiramer acetate ( moderately effective)
 Interferon beta
 Disease modifying therapies..contd
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 Less commonly used agents

 Alemtuzumab (H)
 Mitoxantrone Hydrochloride (H)
 Cladirabine (M)
 Teriflunomide (M)
 Off label treatment options
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 Azathioprine (immunosuppressive)

 Cyclophosphamide (Cyto toxic)

 Treatment of complications
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COMPLICATION TREATMENT

Spasticity Physiotherapy, baclofen, muscle relaxants

Ataxia Cloanzepam

Dysaesthesias Carbamazepine, Phenytion, Gabapentin

Fatigue Amantadine, Modafinil, Amitryptiline

Impotence Sildenafil
 PROGNOSIS
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 About 15% of patients have a single attack of

demyelination and do not suffer further events
 At least partial recovery from acute
exacerbations can reasonably be expected
 Further relapses may occur without warning
 There is no means of preventing progression
of the disorder
 PROGNOSIS
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 Approximately 5% of patients die within

5 years of onset
 95% are alive
 After15 years
 50%patients are unable to walk
 50% are without significant disability

MORE MORBIDITY THAN MORTALITY

Any questions?
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THANK YOU