This document discusses multiple sclerosis (MS), a demyelinating disease of the central nervous system. It begins by defining MS and describing its characteristic features, including inflammation, demyelination, and scarring in the brain and spinal cord. It then covers the clinical manifestations of MS, diagnostic testing methods, treatment approaches including disease-modifying drugs, and potential side effects of treatments.

1. Dr Waqar Ali
Mayo Hospital Lahore

2.  Chronic, progressive, degenerative
disorder of the CENTRAL NERVOUS
SYSTEM characterized by
selective destruction of central nervous
system Myelin..
 The PERIPHERAL NERVOUS SYSTEM is
spared..

3.  It is chacterized by triad of
1. Inflammation
2. Demyelination
3. Gliosis(scarring)

4. Lesions of MS occurs at DIFFERENT TIMES
and in DIFFERENT LOCATIONS in CNS..
MEANS DISSEMINATED IN TIME AND
SPACE,
Manifestations of it vary from a benign
illness to a rapidly evolving and
incapacitating lifestyle adjustments

5.  PHYSIOLOGY:
 Saltatory conduction from one rode of
ranvier to other without depolarization of
the axonal membrane
 Conductin blocks
 Role of Na and k channels

7.  Disease process consists of loss of myelin,
disappearance of oligodendrocytes, and
proliferation of astrocytes
 Changes result in plaque formation with
plaques scattered throughout the CNS

8.  Perivenular cuffing with
 Inflammatory mononuclear cells
 Predominantly T cells and macrophages
 BBB is disrupted
 Myelin specific Autoantibodies
 Heterogenicity
 Shadow plaques
 Relative sparing of axons is typical

10.  Immunology:
 AUTOREACTIVE T LYMPHOCYTES:
Myelin basic protein(MBP) - a T cell antigen
 HUMORAL IMMUNITY:
Autoantibodies
oligoclonal antibodies
 CYTOKINES
IL 2,TNF alpha and gamma
Triggers:
Upper respiratory tract infections

11.  NEURODEGENERATION:
Axonal damage and loss via activated
microglia through the release of NO
,glutamate and oxygen radicals..

12.  EPIDEMOLOGY:
 Usually affects young to middle- aged
adults, with onset between 20 and 40
years of age
 Women affected three times more than
men
 2.5 million population is affected
worldwide

13. EPIDEMOLOGY:
Geographical distribution

14.  Unknown cause
 Related to infectious, immunologic, and
genetic factors

15.  Possible precipitating factors include
Infection like EBV
Physical injury
Emotional stress
Excessive fatigue
Pregnancy
Poor state of health

16.  GENETIC COSIDERATION:
 CAUSCASIONS more prone as compared
to asians or africans
 POLYGENIC
 MHC on chromosome 6 specifically DR2

17. • Relapsing-remitting MS (RRMS)
–Affects 85% of newly diagnosed
–Characterized by Discrete attacks
–Attacks followed by partial or complete
recovery
–Between attacks patients are
neurologically stable

18. • Secondary-progressive MS (SPMS)
 Always begins as RRMS
Occasional relapses but symptoms remain
constant, no remission
Progressive disability late in disease course
Steady deterioration in functions unassociated
with acute attacks
Seems to be a late stage of RRMS

19. Primary-progressive MS (PPMS)
◦ Affects approximately 15% of MS
population
◦ Slow onset but steady functional
deterioration from disease onset
◦ These usually do not experience attacks

20.  Progressive-relapsing MS (PRMS)
◦ Rarest form
◦ Affects approx. 5%
◦ Steady worsening of condition
at onset

23.  Abrupt or insidious
 Severe or trivial
 Depends upon location and severity

24. initial symptoms of MS
symptom Percent of cases symptom Percent of cases
Sensory loss 37 Lhermitte 3
Optic neuritis 36 Pain 3
Weakness 35 Dementia 2
Paresthesias 24 Visual loss 2
Diplopia 15 Facial palsy 1
Ataxia 11 Impotence 1
Vertigo 06 Myokymia 1
Paroxysmal
attacks
04 Epilepsy 1
Bladder 04 Falling 1

25.  Motor manifestations
◦ Weakness or paralysis of limbs, trunk, and head
are of upper motor neuron type
◦ Diplopia (double vision)
internuclear ophthalmoplagia
horizontal gaze palsy
Nystagmus
◦ Scanning speech
◦ Spasticity of muscles

27.  Sensory manifestations
◦ Numbness and tingling, formication “pins and
needles” or unpleasant sensations or a dead
feeling..
◦ Optic neuritis
◦ Blurred vision
◦ Vertigo and tinnitus
◦ Decreased hearing
◦ Chronic neuropathic pain

28.  Cerebellar manifestations
◦ Nystagmus
 Involuntary eye movements
◦ Ataxia
◦ Dysarthria(scanning speech):
 Lack of coordination in articulating
 speech
◦ Dysphagia
 Difficulty swallowing

29.  Emotional manifestations
◦ Anger
◦ Depression
◦ Euphoria

30.  Bladder dysfunction
detrusor hyper reflexia and
detrusor sphincter dyssynergia
 Constipation
 Sexual dysfunction
 Fatigue
 Facial weakness
 Vertigo

31.  Uhthoff’s symptoms:
unilateral visual blurring during a hot shower
or physical exercise
 Lhermitte’s symptoms:
electrical shock like sensations by flexion of
neck
 Paroxysmal symptoms:
Brief duration,high frequency,lack of ASOC,self
limited course
 Trigeminal neuralgia
 Facial myokymia

33.  Viral infections like HIV
 Lyme disease
 B12 deficiency
 Stroke
 SLE And Other connective tissue disorders
 Rheumatoid arthritis
 Vasculitis
 Syphilis
 Tuberculosis
 Vascular malformations
 Sarcoidosis

34.  There is no definative diagnostic tests for
MS
 Its based on history and clinical
examination
 Two or more symptoms or signs that
reflect pathology in anatomically
noncontiguous white matter tracts of CNS
 Must lasts>24 hrs and occurs as distinct
episodes that are separated by a month
or more

35. MAGNETIC RESONANCE
IMAGING:
 it demonstrates presence of plaques(a
focal area of hyperintensity)
 Done with intravenous Gadolinium
 Dawson’s fingers: lesions are usually
perpendicular to venticular surface
 lesions> 6mm or located in corpus
collasum,periventicular white mater,brain
stem,cerebellum, or spinal cord

39.  EVOKED POTENIALS:
Assess functions in afferent and
efferent CNS pathways by repetitive
stimuation

40.  CEREBROSPINAL FLUID:
increased levels of intrathecally
synthesized IgG
Total CSF protiens may be normal
IgG index: ratio of IgG to albumin in CSF to
same in serum
OLIGO CLONAL BANDING:

41.  Other tests
Like serum B12 levels,
ANA,ESR,trepoemal antibodies

43.  GOOD PROGNOSIS:
Optic neuritis or sensory symptoms at
onset
Fewer than 2 relapses in first year
Minimal impairement after 5 years

44.  Bad prognosis:
Truncal ataxia
Action tremors
Pyramidal symptoms
Progressive disease course

45. Kurtzke expanded disability score

47. 1. Treatments of acute attacks as they
occur
2. Treatment with disease modifying
agents
3. Symptomatic therapy

48.  Acute attacks:
First think is it acute attack or
PSEUDOEXACERBATION?
Pseudoexacerbation are usually not treated

49. CORTICOSTEROIDS:
 Treat acute exacerbations by reducing edema and
inflammation at the site of demyelination
 Do not affect the ultimate outcome or degree of
residual neurologic impairment from exacerbation
 Administered as intravenous
METHYLPREDNISOLONE 500-1000mg/day for3 to 5
days followed by oral prednisone 60-80mg/day with
gradually tapered over 2 weeks

50.  PLASMA EXCHANGE:
seven exchanges 40-60ml/kg per exchange
every other day for 14 days
But evidence of efficacy is only preliminary

51.  Selective immunomodulation
◦ Glatiramer acetate (Copaxone)
 Nonspecific immunomodulation
◦ IFN b-1a (Avonex, Rebif)
◦ IFN b-1b (Betaferon)
 Selective adhesion molecule inhibitor
◦ Natalizumab (Tysabri)
 Immunosuppression
◦ Mitoxantrone (Novantrone)

52.  Others:
 Methotrexate
 Cyclophosphamide
 Intravenous immunoglobulins

53.  IFN b: (Avonex, Rebif,Betaseron)
 Induces an antiproliferative effect
 Blocks T cell activation
 Induces apoptosis of autoreactive T cells
 IFN- antagonistic
 Has antiviral effect
 Acts in periphery (ie, does not cross BBB)
 Indirect effects on CNS

54.  IFN b:
Reduces attack rates
Improves disease severity measures like
EDSS
Can be use in RRMS ,SPMS with relapses
INF b 1a 30ug by intramuscular injections
once every week
INF b 1b 250ug by subcutaneous
injections every other day

55.  :GLATIRAMER ACETATE (Copaxone)
 Blocks autoimmune T cells
 Binding to MHC molecule so displace MBP
 Induces anti-inflammatory TH2 cells
 Upregulates neuronal preservation
 Augmentation of processes of neurogenesis:
cell proliferation, migration, differentiation

56.  GLATIRAMER ACETATE:
 Reduce attack rates
 Used in only RRMS not in progressive
 20mg every day by subcutaneous
injections

57.  NATALIZUMAB: (Tysabri)
 Primary mechanism related to blockade
of
interaction between the a4b1-integrin
which is expressed on T lymphocytes
brain receptors so prevent there entry
through BBB..

58.  NATALIZUMAB:
Reduces attack rates
Significantly improves all measures of
disease severity
300ug by intravenous infusions every
month

59.  Mitoxantrone (Novantrone) :
◦ Antineoplastic drug
◦ Acting by interlacing into DNA and producing
strand breaks,iterfering with RNA synthesis
and inhibiting topoisomeras..
◦ Indicated in RRMS,SPMS and in worsening
RRMS
◦ 12mg/m2

61.  Side effects of disease modyfying agents:
 Local injection site irritation/reactions
 Flu like symptoms
 Rise in liver enzymes
 Decreased white cell count and platelets
 Opportunistic infections
 Depression
 Progressive multifocal leukoencephalopathy
(PML)
 Cardiotoxicity with mitoxantrone