Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by inflammation and nerve damage. It commonly affects women under 30 years old in temperate climates. Symptoms include visual problems, numbness, weakness, and impaired coordination. While relapses may be followed by remission, over time disability accumulates without treatment. The cause is unknown but involves immune-mediated damage to myelin. Diagnosis is clinical based on dissemination of lesions in time and space. MRI is used to identify lesions. Treatment focuses on reducing relapse rate and progression with steroids, interferons, glatiramer acetate or monoclonal antibodies.

1. DR. SIKANDER ALI
26-12-2013

2. Definition
Multiple Sclerosis is a relapsing/remitting
disorder, consists of plaques of demyelination (and
axon loss) at sites throughout the CNS (but not
peripheral nerves).

4. Pathogenesis
Pathogenesis involves focal disruption of the blood
brain barrier and associated T cell mediated immune
response and myelin damage, the trigger however is
unknown.

5. Epidemiology
It is commoner in temperate areas, rare in Africa and
Asia. Mean age of onset is 30 yrs, female to male ratio
is 3:1

6. Presentation
is usually monosymptomatic: unilateral optic neuritis
(pain on eye movement and rapid deterioration in
central vision); numbness or tingling in the limbs; leg
weakness or brainstem or cerebellar symptoms such as
diplopia or ataxia. Less often there may be more than 1
symptom. Symptoms may worsen with heat (eg a hot
bath) or exercise.

7. Progression
Initially demyelination may be followed by full
recovery, but with time remissions are incomplete so
disability accumulates. Prolonged demyelination
causes axonal loss and clinically progressive
symptoms, while some patients experience no
progressive disablement at all.

8. Varieties of MS
Four general categories:
• Relapsing-remitting MS(RRMS) is characterized by recurrent attacks
of neurologic dysfunction usually with or without recovery, between
attacks, no progression of neurologic impairment is noted. Accounts
for 85% of new-onset MS cases.
• Secondary progressive MS(SPMS) always initially presents as RRMS
but evolves to be gradually progressive. The majority of RRMS
eventually evolves into SPMS.
• Primary progressive MS(PPMS) is characterized by gradual
progression of disability from onset without discrete attacks; 15% of
new-onset MS cases.
• Progressive-relapsing MS(PRMS) is a rare form that begins with a
primary progressive course, but later superimposed relapses occur.

9. Clinical Features
Sensory:
Motor:
Cord:
Dysaesthesia (abnormal sensation like
pins and needles, vibration, burning or
crawling) and trigeminal neuralgia
Spastic weakness, hyper reflexia
Transverse myelitis (Loss of
motor, sensory, autonomic, reflex, and
sphincter function below the level of a
lesion), bowel dysfunction,urinary
urgency or retention, anorgasmia and
erectile dysfunction.

10. Ocular:
Cerebellum:
Diplopia, hemianopia, optic
neuritis, nystagmus in the abducting eye
on lateral gaze. Pupillary defects
(Efferent, afferent or relative afferent) and
visual phenomenon (Uhthoff's
phenomenon: vision worsens on
exercise, eating a hot meal, or in hot
baths)
Truncal or limb ataxia, intention
tremor, dysarthria, scanning
(monotonous) speech, falls

11. GIT:
Cognitive:
Other:
Swallowing
disorders, constipation.
Cognitive and visuospatial decline
is a big cause of
unemployment, accidents and
isolation
Fatigue, depression, mania, odd
laughter

14. Diagnosis
Diagnosis is clinical! as no test is pathognomonic. It
requires demonstration of lesions disseminated in
time and space; and patient’s neurologic condition
could not better be attributed to another disease.
McDonald criteria is often used to diagnose MS but it
accord too much weight to MRI.

15. Clinical presentation Additional data needed
2 or more attacks with 2 or more
objective clinical lesions
None; clinical evidence will do; imaging evidence
desirable; must conform to MS
2 or more attacks with 1 objective
clinical lesion
Typical disseminated lesions on MRI or +ve CSF
and MRI lesions consistent with MS or 2nd attack at
a new site
1 attack with 2 or more objective
clinical lesions
Dissemination in time, shown by MRI or 2nd clinical
attack
1 attack with 1 objective clinical
lesion (monosymptomatic attack)
Dissemination in space:
*MRI or +ve CSF if MRI lesions consistent with MS
*and dissemination in time shown by MRI or 2nd
clinical attack

16. Continued…
Clinical presentation Additional data needed
Insidious neurological progression
suggestive of MS (primary progressive
MS)
+ve CSF and dissemination in space, ie:
MRI evidence of T2 brain lesions
or 2 or more cord lesions
or 4-8 brain and 1 cord lesion
or +ve (VEP) with 4-8 MRI lesions
or +ve VEP + <4 brain lesions + 1 cord lesion and
dissemination in time seen on MRI
or continued progression for 1yr
Attacks: These must last >1h, eg motor weakness
etc
Time between attacks: 30 days

17. MRI findings in MS
A. Axial first-echo image
from T2-weighted sequence
demonstrates multiple
bright signal abnormalities
in white matter, typical for
MS.
B. Sagittal T2-weighted
FLAIR image in which the
high signal of CSF has been
suppressed. CSF appears
dark, while areas of brain
edema or demyelination
appear high in signal as
shown here in the corpus
callosum (arrows). Lesions
in the anterior corpus
callosum are frequent in MS
and rare in vascular disease

18. MRI findings in MS
Left. Sagittal T2-weighted
fast spin echo image of the
thoracic spine
demonstrates a fusiform
high-signal-intensity lesion
in the mid thoracic spinal
cord.
Right. Sagittal T1-weighted
image obtained after the
intravenous administration
of gadolinium DPTA
reveals focal areas of
blood-brain barrier
disruption, identified as
high-signal-intensity
regions (arrows)

19. MRI findings in MS

20. Treatment
 Methylprednisolone: 1g/24h IV/PO for 3d shortens
relapses; use sparingly, It does not alter the overall
prognosis.
 Interferon (IFN-1B and IFN-1a): Decreases relapses by
~30% in active RRMS, they also decrease lesion
accumulation on MRI. Their power to decrease disability is
modest, as is their role in secondary and primary
progressive (SP & PP) MS.
 Glatiramer: is a similar alternative to IFN.

21.  Azathioprine: may be as effective as interferons for RRMS
and is 20X cheeper.
 Monoclonal Antibodies: Alemtuzumab and Natalizumab, acts
against T-cells and are considered 2nd line agents in RRMS.
 Mitoxantrone (doxorubicin analogue): helps in 2dry
progressive MS
 Other: for spasticity: baclofen, diazepam, dantrolene and
tizanidine can be used. For urgency and frequency oxybutynin
my prove useful.
 There is no good, safe preventive treatment for those with
primary progressive MS

24. CLINICAL VARIANTS OF MS
 Neuromyelitis optica(NMO) also known as Devic’s
syndrome consists of separate attacks of acute optic
neuritis (bilateral or unilateral) and myelitis. In
contrast to MS, the brain MRI is typically, but not
always, normal. A focal enhancing region of swelling
and cavitation, extending over three or more spinal
cord segments, is typically seen on spinal MRI. Acute
attacks are usually treated with high-dose
glucocorticoids as for MS exacerbations.

25. CLINICAL VARIANTS OF MS
 Acute MS(Marburg’s variant) is a fulminant
demyelinating process that progresses to death within
1–2 years. No controlled trials of therapy exist, high
dose glucocorticoids, plasma exchange, and
cyclophosphamide have been tried, with uncertain
benefit.

26. Differentials
 Acute disseminated encephalomyelitis (ADEM)
 Antiphospholipid antibody syndrome
 Behçet’s disease
 Human immunodeficiency virus (HIV) infection
 Ischemic optic neuropathy (arteritic and nonarteritic)
 Neoplasms (e.g., lymphoma, glioma, meningioma)
 Systemic lupus erythematosus and related collagen vascular disorders
 Vascular malformations (especially spinal dural AV fistulas)
 Vitamin B12deficiency
 Vasculitis (primary CNS or other).

27. Thank You