A presentation on multiple sclerosis including pathogenesis ,clinical presentation and treatment options .

1. MULTI
PLE
SCLER
OSIS
Dr.Tareq Esteak
Resident
NINS

2. MULTIPLE SCLEROSIS
Multiple Sclerosis is an autoimmune
disease of the central nervous system
characterized by
Chronic inflammation,
Demyelination,
Gliosis
Neuronal loss.

3. EPIDEMIOLOGY
More common in female
Age onset 20 to 40
Temperate zone(Scotland*,North America,
Australia and New zealand)

4. EPIDEMIOLOGY

5. RISK FACTORS
 Genetic predisposion
 Vitamin D deficiency
 Epstein-Bar virus exposure after early
childhood
 Cigarette smoking
N.B: Vitamin D deficiency also increase disease
activity in MS patients.

6. PATHOGENESIS

7. PHYSIOLOGY

8. PATHOLOGY

19. CLINICAL FEATURE
Sensory loss(38%)
Optic neuritis(37%)
Weakness(36%)
Transverse Myelities (Clinically isolated syndrome)
Cerebellar ataxia
Brain stem syndrome
Vertigo
Facial pain
Dysarthria
Diplopia

21. ANCILLARY SYMPTOMS
Lhermitte’s symptoms
Heat sensitivity(Uhthoff’s symptom)
Tonic contraction of a limb, face or trunk(tonic
seizure)
Paroxysmal sensory disturbances
Trigeminal neuralgia
Facial myokymia

23. TYPES

24. DIAGNOSIS
There are five principles for diagnosis of
MS
1. Identification of symptoms typical of MS
related demylination
2. Objective evidence of CNS involvement
3. Demonstration of dissemination in space
4. Demonstration of dissemination intime
5. No better explanation other then MS

25. DIAGNOSTIC TEST
There is no single dignostic
test for MS
Diagnostic tools are
MRI
Evoked Potentials
Cerebrospinal fluid

26. DIAGNOSTIC CRITERIA
FOR MS

27. MRI
Revolutionized the diagnosis and
management of MS
Characteristic abnormalities are
found >95% of patients

28. MRI: TYPICAL SITES OF
MS

29. MRI:DIT & DIS
Dissemination in Time
MRI can demonestrate
dissemination of time by
the presence of gadolinium
–enhancing and
nonenhancing lesions in
same film or by the
appearance of a new T2-
hyperintence or
gadolinium –enhancing
lesions on a follow up MRI.
Dissemination of space
MRI demonestrate
dissemination of space if
at least one T2 –
hyperintense lesion found
two of the following region
1. Periventricular
2. Cortical or
juxtracortical
3. Infratentorial
4. The spinal cord

30. EVOKED POTENTIALS
Afferent: Visual, Auditory, Somatosensory
Efferent: Motor
Not specifice for MS but Suggestive
Abnormalities on one or more EP
modalities occur in 80-90% of MS
patients.

31. CEREBROSPINAL FLUID
CSF monoeuclear pleocytosis (more then 5
cells/uL in 25%)
CSF protein usually normal or mildly elevated
Protein concentration more then 100mg/dl
and pleocytosis more then 75 cells/uL raise the
concern that patient may not have MS.

32. CEREBROSPINAL
FLUID:IGG INDEX
The CSF IgG index is often
used to help diagnose
multiple sclerosis (MS), but
it is not specifically an MS
test.
Normal value is <0.7
Increased value means
local production of IgG
rather than infusion from
blood
Increased in : MS ,SSPE

33. CEREBROSPINAL
FLUID:OCB
Oligoclonalbands are bands of
immunoglobulins that are seen when
serum/csf is analyzed.
CSF OCBs (may be absent at onset and
number of OCBs may increase with time)
>2 discrete OCBs, not present in a
paired serum sample , taken
simultaneously found around 75% of
cases.

34. VARIANTS OF MULTIPLE
SCLEROSIS

35. T1WI C+Large
hypointense area with
incomple ring
enhancement, a
classical Tumefective
MS
MRS: shows large choline
pick with low NAA.(tumor
like)
Prefusion scan: rCBV
reduced in
demyelinationbut
increased in tumor.

36. MARBURG
DISEASE
(ACUTE
FULMINANT
MS)
T1WI C+ :Large
Enhancing
demyelinating lesion
in deep and
periventricular white
matter lesion

37. BALO’S
CONCENTRIC
MS
T1WI C+ :
showsConcentriclaminat
ed “ONION BULB”
appearance.
This is a rare aggresive
variant MS where
patients usually
presents with rapid
onset worsening
symptoms.

38. BLACK
HOLES
T1WI shows multiple
hypointense lesion
in the periventricular
area related to
Axonal
destruction.Note,
moderate ventricular
and sulcal
enlargement.

39. MS MIMICS
Many Neurological disease may mimic
MS clinically and/ radiologically.
Most common MS mimics are of
vascular origin.
The possible differentials for white-
matter lesion are long.

40. SMALL
VESSEL
DISEASE
(LEUKOARAI
OSIS)
Multiple white
matter lesion near
the ventricles and
sub-cortical space.
May give history of
HTN,DM or
Homocystinurea

41. MS VS
VASCULAR(LEUKOARAO
SIS)

42. MS: FLAIR
• Juxtra-cortical/u fibre
involvement.
• Corpus callosal
involvement.
• Tempor.
• Peri-ventricular
distribution.
• Dawson finger present
• Tempora
lobe,infratentoreal,s.cord
involvement.
Vascular:T2 WI
• Sub-cortical distribution
• Lesion doesn’t touch the
cortex.
• Asysmtrical distribution.
• Dawson finger absent
• No temporal or
infratentorealor s.cord
involvement.

43. MS VS NMO
• A very important
differential to keep in
mind, especially in
patients with a bilateral
optic neuritis
• We should think of NMO
when there are extensive
spinal cord lesions (more
than 3 vertebral
segments) with low T1-
signalintensity and
swelling of the cord.
• Often there are few/no
T2-lesions in the brain.
• The clue to the diagnosis
is the high AQP4-AB titer

44. ADEM VS MS

45. ADEM VS MS

46. MS VS METS
PERILESIONAL EDEMA
GOES IN FAVOR OF
METS
SINGLE,LARGE, RING
ENHANCEMENT GOES
INFAVOR OF METS THAN
MS

47. SARCOIDOSI
S VS MS
• Multi-system disorder.
• Associated Respiratory,
cardiovascular and skin
manifestation may be
present.
• The distribution of lesions is
quite similar to MS.
Besides lesions in the deep
WM, there are some
juxtaiventricular lesions and
even Dawson finger-like
lesions.
• Typical for sarcoid in this
case is the leptomeningeal

48. SARCOIDOSIS VS MS
T1WI C+:
Leptomeningeal
Enhancement
T1WI C+: Linear
enhancement due to
inflammation of vircow
Robbin’s space.

49. PML VS MS
•Caused by JC virus in
immunosuppressed
patients.
•Usually have history of
HIV infection or
treatment with
monoclonalantibodylik
e Natalizumab.
•Lesion usually are
subcortical, diffuse, ill
defined, usually size
>5mm (MS-<5mm)

50. MS VS
CADASIL
• Cerebral Autosomal Dominant
Arteriopathy with Subcortical
Infarcts and
Leukencephalopathy.
• Clinical clues: family history
migraine, dementia.
• MRI:fLAIR shows Multiple sub-
cortical infracts
WMLs in the anterior temporal pole
and external capsule

51. TREATMENT

52. ACUTE ATTACK
Intravenous Methylprednesolone 500 to
1000mg/day for 5 days without an oral tapper.
Alternatively, Oral steroid is effective as the IV
infusion.
Patients who cant tolerate oral steroid with
poor venous access IM/SubQ corticotropin gel
may be used.
In patients with severe neurological deficit
refractory to high dose steroid, plasma
exchange is another option.

53. DISEASE MODIFYING
THERAPIES
GOAL:
A decrease in relapse rate.
A slower accumulation of brain lesion
on MRI
Lower the risk of disease progression.

54. WHAT DMT TO CHOOSE?
High
diseas
e
activity

55. WHAT DMT TO CHOOSE?
PPMS(PrimaryProgressive
MS)
Ocrelizumab

56. SPMS
(Secodary Progressive MS)
IFN-B(if Active)
Mitoxantrone
(lack in evidence)

57. MECHNISM OF ACTION:
DMTS

58. MECHNISM OF ACTION
DMF

59. MONITORING
RESPONSE
Tools:
Clinical followup
MRI brain:
o Before starting or changing DMT
oAfter 6months
o After that,annually
oPCR-Jcvirus -6monthly-for patients on
Natalezumab
Expanded disability status scale – 3monthly

60. Patient refractory to initial DMT change into another 1st
line drug.
(single mild relapse or a single lesion within 6month is not refractory
MS)
Recommendations:
If initially treated with glatiramer or inf-beta switch to-
•Di-methylfumerate, Fingolimod or Teriflunamide.
Or
•Natalezumab or Ocrelezumab.
 Initially treated with Natalezumab who have inadequate
response or developed PML-
•Stop the drug and switch to Ocrelezumab or Alemtuzumab
REFRACTORY DISEASE

61. PREGNANCY
Data shows activity of MS isreduced during
pregnancy.
Baby child may beborn with IUGR or congenital
fetal malformations.
Drug should be avoided are –Fingolimod and
Mitoxantrone.
Druds that are safe are- Glatiramer,Inf,
Alamtuzumab, Natalizumab etc

62. OFF LABEL TREATMENT
OPTIONS
Options Preferred situation Drawback
Azathioprine rrMS Benefit on disability progression yet
to be demonstrated.
Methotrexate SPMS Irreversible liver damage,
Cyclophosphamide Treatment-refractory MS-
Abmulatory, <40y, apperntly in
good health
Bladder carcinoma, Hemorrhagic
cystitis
Intravenous
immunoglobulin
monthly pulses (up to 1 g/kg) for
up to 2y, appears to reduce
annual exacerbation rates
High cost
Methylprednisolone in one study, administered as
monthly iv pulses, reduced
disability progression
Steroid related Side effects
Hematopoietic stem cell
transplantation
rrMS: highly effective in reducing
the occurrence of relapses and
may improve disability in
procedure carries a significant
mortality risk

63. COVID-19 RELATED
UPDATE
Available data shows that DMT does not
increase the risk of COVID-19
DMT was not associated with increase severity
of Covid-19.

64. THANK YOU….