IS IT INCREASING

2. MULTIPLE SCLEROSIS
 Inflammation
 Demyelination
 Gliosis(scarring)
 Can be relapsing remitting or progressive
 Lesions are typically disseminated in time and location

3. anatomy
 Lesions size 1-2 mm to several centimeters
 Perivenular cuffing with inflammatory mononuclear
cells
 BBB disrupted at sites of inflammation
 Vessel wall is spared unlike in vasculitis
 Myelin specific autoantibodies promote
demyelination,Astrocytes proliferate(gliosis)
 Remyelination by surviving oligodendrocytes leads to
shadow plaques

4. physiology
 Nerve conduction in myelinated axons occurs in
saltatory manner
 Conduction block occurs when impulse is unable to
traverse demyelinated segment

5. epidemiology
 Twice common in women than in men
 Age of onset 20-40 yrs
 Highest prevalence in orkney islands followed by
northern Europe,north america,canada
 Low in japan,other Asian countries,equitorial
africa,middle east
 Indian – prevalence <5 cases per 100,000
 Highest prevalence in parsis-26/100,000.
 Prevalence increases with increasing distance from
equator

6. Genetics
 Genetic susceptibility to MS exists
 Life time risk to sibling of affected 2%-5%
 Concordance rate in monozygotic twins 25%-35%
 Concordance rate in dizygotic twins 2%-5%
 Inheritance is probably poly genic

7. Immunology&microbiology
 Auto antibodies directed against myelin antigens such
as myelin oligodendrocyte glycoprotein(MOG)act in
concert with a pathogenic auto reactive T lymphocyte
response to cause demyelinating lesion
 MS risk is high in high SE status(delayed exposure to
infectious agents)
 High antibody titers against many viruses are seen in
csf and serum
 Molecular mimicry between viruses and myelin
antigen may play role in MS pathogenesis

8. Clinical features of MS
 Weakness of limbs(UMN type)
 Loss of strength
 Fatigue
 Gait disturbance
 Exercise induced weakness
 Spasticity
 Hyper reflexia
 babinski

9. Optic neuritis
 Decreased visual acuity
 Decreased color perception in central field
 Usually mono ocular may be binocular sometimes
 Peri orbital pain precedes visual loss
 Optic atrophy usually follows

10. diplopia
 Results from inter nuclear ophthalmoplegia(INO)
 MLF lesion –impaired adduction on same
side,prominent nystagmus in abducting eye
 Horizontal gaze palsy
 One and a half syndrome(horizontal gaze palsy+INO)
 Acquired pendular nystagmus

11. Other symptoms
 Sensory-parasthesias,hypesthesia
 Ataxia-usually late manifestation
 Intention tremor,scanning speech,nystagmus-
CHARCOT”S triad
 Bladder& bowel dysfunction
 Cognitive dysfunction
 Depression
 Fatigue
 Sexual dysfunction

12. Ancillary symptoms
 Heat sensitivity
 Visual blurring with hot showers(uthoff”s
phenomenon)
 Lhermitte”s symptoms
 Paroxysmal symptoms
 Trigeminal neuralgia
 Hemi facial spasm
 Glosso pharyngeal neuralgia

13. Disease course
 Relapsing, remitting MS(RRMS)-85%,acute attacks
and complete recovery
 Secondary progressive MS(SPMS)-starts as RRMS at
some point changes to steady detoriation
superimposed on acute attacks
 Primary progressive MS(PPMS)-15%-no attacks ,steady
decline from disease onset, more even sex
distribution, mean age 40 yrs,develops faster
 Progressive relapsing MS(PRMS)-steady detoriation
from onset,superimposed attacks on progressive
course

14. Diagnostic criteria
1.Examination must reveal objective abnormalities of CNS
2.Involvement of predominantly disease of white matter long tract-
pyramidal,cerebellar,MLF,optic nerve,post.columns
3.Examination or history must implicate involvement of two or more
areas of CNS
(a)MRI-MCDONALD’S – criteria-
three out of four(1)one Gd enhancing lesion or nine T2 hyper intense
lesions(2)at least one infra tentorial lesion(3)at least one juxta cortical
lesion((4)at least three peri ventricular lesions
(b)evoked response testing may be used to document lesion
4.Clinical pattern(a)two or more episodes of worsening involving
different sites of CNS each lasting >24 hrs at least 2 months
apart(b)gradual or stepwise progression over 6 months
5.The neurological condition cannot be attributed to another disease

15. Diagnostic categories
 Definite MS-all 5 fulfilled
 Probable MS-all 5 fulfilled except(a)one objective
abnormality despite two symptomatic episodes
or(b)one symptomatic episode despite two objective
abnormalities
 At risk for MS-criteria1,2,3,5 fulfilled; patient has only
one symptomatic episode and one objective
abnormality

16. Diagnostic tests
 MRI-hyper intense T2 lesions oriented perpendicular
to ventricular surface(DAWSON’S fingers),irreversible
de myelination –hypo intense onT1
 EVOKED POTENTIALS-visual, auditory,somato
sensory-marked delay in latency suggest
demyelination
 CSF-mononuclear cell pleocytosis,IgG >12% of total
protein,csf IgG index>1.7,two or more oligoclonal
bands in csf

17. MRI in MS

18. Differential diagnosis
 ADEM,
 anti phospholipid antibody syndrome,
 bechet’s disease,
 CADASIL,
 congenital leukodystrophy,
 HIV,
 MELAS,
 SLE,
 B12 def.etc

19. Suspect Alternate diagnosis if
 Symptoms localized exclusively to post.fossa
 Age of onset<15,>60 yrs
 Clinical course progressive from onset
 Who never experience visual,sensory,bladder
symptoms
 Atypical lab findings
 Rare symptoms like aphasia,chorea, seizures

20. Good prognostic indicators
 Optic neuritis,sensory symptoms at onset
 Who recovers completely from early attacks
 <40 yrs at onset
 Women
 RRMS
 <2 relapses in first year
 Minimal impairment after 5 yrs

21. Poor prognostic factors
 Childhood onset
 Age of onset>40
 Truncal ataxia
 Action tremor
 Pyramidal symptoms
 Progressive disease

23. treatment
 Acute attacks-gluco corticoids,iv methyl prednisolone
500-1000 mg /day for 5 days;
 plasma exchanges ,7 exchanges EOD for 14 days
 Disease modifying therapies for relapsing forms-
 interferons-beta,
 glatiramer acetate,
 mitoxantrone,
 natalizumab,
 Symptomatic treatment