MULTIPLE SCLEROSIS

MULTIPLE SCLEROSISInflammationDemyelinationGliosis(scarring)

Can be relapsing remitting or progressiveLesions are typically disseminated in time

and location

anatomyLesions size 1-2 mm to several centimetersPerivenular cuffing with inflammatory

mononuclear cellsBBB disrupted at sites of inflammationVessel wall is spared unlike in vasculitisMyelin specific autoantibodies promote demyelination,Astrocytes proliferate(gliosis)Remyelination by surviving oligodendrocytes

leads to shadow plaques

physiologyNerve conduction in myelinated axons occurs

in saltatory manner Conduction block occurs when impulse is

unable to traverse demyelinated segment

epidemiologyTwice common in women than in menAge of onset 20-40 yrsHighest prevalence in orkney islands followed

by northern Europe,north america,canadaLow in japan,other Asian countries,equitorial

africa,middle eastIndian – prevalence <5 cases per 100,000Highest prevalence in parsis-26/100,000.Prevalence increases with increasing distance

from equator

GeneticsGenetic susceptibility to MS existsLife 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

Immunology&microbiologyAuto 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

Clinical features of MSWeakness of limbs(UMN type)Loss of strengthFatigueGait disturbanceExercise induced weaknessSpasticityHyper reflexiababinski

Optic neuritisDecreased visual acuityDecreased color perception in central fieldUsually mono ocular may be binocular

sometimesPeri orbital pain precedes visual lossOptic atrophy usually follows

diplopiaResults from inter nuclear

ophthalmoplegia(INO)MLF lesion –impaired adduction on same

side,prominent nystagmus in abducting eyeHorizontal gaze palsyOne and a half syndrome(horizontal gaze

palsy+INO)Acquired pendular nystagmus

Other symptomsSensory-parasthesias,hypesthesiaAtaxia-usually late manifestationIntention tremor,scanning speech,nystagmus-

CHARCOT”S triadBladder& bowel dysfunctionCognitive dysfunctionDepressionFatigueSexual dysfunction

Ancillary symptomsHeat sensitivityVisual blurring with hot showers(uthoff”s

phenomenon)Lhermitte”s symptomsParoxysmal symptomsTrigeminal neuralgiaHemi facial spasmGlosso pharyngeal neuralgia

Disease courseRelapsing, remitting MS(RRMS)-85%,acute attacks

and complete recoverySecondary 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

Diagnostic criteria1.Examination must reveal objective abnormalities of CNS2.Involvement of predominantly disease of white matter long tract-

pyramidal,cerebellar,MLF,optic nerve,post.columns3.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 lesion4.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

Diagnostic categoriesDefinite MS-all 5 fulfilledProbable 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

Diagnostic testsMRI-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

MRI in MS

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

Suspect Alternate diagnosis ifSymptoms localized exclusively to post.fossaAge of onset<15,>60 yrsClinical course progressive from onsetWho never experience visual,sensory,bladder

symptomsAtypical lab findingsRare symptoms like aphasia,chorea, seizures

Good prognostic indicatorsOptic neuritis,sensory symptoms at onsetWho recovers completely from early attacks<40 yrs at onsetWomenRRMS<2 relapses in first yearMinimal impairment after 5 yrs

Poor prognostic factorsChildhood onsetAge of onset>40Truncal ataxiaAction tremorPyramidal symptomsProgressive disease

treatmentAcute attacks-gluco corticoids,iv methyl

prednisolone 500-1000 mg /day for 5 days;plasma exchanges ,7 exchanges EOD for 14

daysDisease modifying therapies for relapsing

forms-interferons-beta,glatiramer acetate,mitoxantrone,natalizumab,Symptomatic treatment