Case historyCase history

• A 32yrs old lady is brought to ER with A 32yrs old lady is brought to ER with c/o gradually developing weakness of c/o gradually developing weakness of left half of body for last 5 days. Now left half of body for last 5 days. Now there is weakness of right arm as there is weakness of right arm as well. No h/o fever, headache, well. No h/o fever, headache, vomiting or unconsciousness.vomiting or unconsciousness.

O/EO/E

• GPE normalGPE normal

• CNS:CNS:

Power 2/5 in left arm & legPower 2/5 in left arm & leg

3/5 in right arm3/5 in right arm

left facial nerve palsy LMN typeleft facial nerve palsy LMN type

left plantar upgoingleft plantar upgoing

reflexes brisk on left side reflexes brisk on left side

• What is your DD?What is your DD?

• How will you proceed?How will you proceed?

How will you explain the disease?How will you explain the disease?

Case historyCase history

• A 35 yr old gentleman presents with A 35 yr old gentleman presents with sudden onset paraplegia. O/E there is sudden onset paraplegia. O/E there is UMN paraplegia with a sensory level UMN paraplegia with a sensory level at T8.at T8.

• h/o sudden transient unilateral visual h/o sudden transient unilateral visual loss 7 yrs back.loss 7 yrs back.

• Whats the pathology?Whats the pathology?

Case historyCase history

• A young girl of age 17 presents in A young girl of age 17 presents in opd with c/o diplopia & unsteadiness opd with c/o diplopia & unsteadiness developing over 2months. O/E :developing over 2months. O/E :

• Features of right cerebellar lesionFeatures of right cerebellar lesion

• Bilaterally upgoing plantarsBilaterally upgoing plantars

• Left lateral rectus palsyLeft lateral rectus palsy

All routine labs are normalAll routine labs are normal

Give your diagnosis?Give your diagnosis?

Case historyCase history

• A diagnosed patient of multiple A diagnosed patient of multiple sclerosis presents with complaints of sclerosis presents with complaints of severe excruciating pain over left severe excruciating pain over left half of face. There is electric spark half of face. There is electric spark like sensation. Pain aggravates even like sensation. Pain aggravates even on touching the face. Its not relieved on touching the face. Its not relieved even by use of NSAIDs.even by use of NSAIDs.

• What is the underlying problem?What is the underlying problem?

DefinitionDefinition

• Chronic inflammatory demyelinating Chronic inflammatory demyelinating disorder affecting CNS characterized disorder affecting CNS characterized by relapses and remissionsby relapses and remissions

• Also called as Also called as disseminated sclerosisdisseminated sclerosis or or encephalomyelitis disseminataencephalomyelitis disseminata

• French neurologist French neurologist Jean Martin Jean Martin CharcotCharcot was the first to recognize was the first to recognize multiple sclerosis as a distinct multiple sclerosis as a distinct separate disease in 1868separate disease in 1868

EpidemiologyEpidemiology

• Male: Female= 1:2Male: Female= 1:2

• Peak age of onset is in the fourth decadePeak age of onset is in the fourth decade

• Incidence varies with latitude, low in Incidence varies with latitude, low in equatorial areas and higher in temperate equatorial areas and higher in temperate zoneszones

• More relapses occur during spring and More relapses occur during spring and summersummer

AetiologyAetiology

Genetic factorsGenetic factors

• Environmental factorsEnvironmental factors

• Autoimmune factors Autoimmune factors

The risk of familial recurrence is 15% The risk of familial recurrence is 15% with highest being for first degree with highest being for first degree relatives.relatives.

Monozygotic twin concordance is 35%Monozygotic twin concordance is 35%

PathologyPathology

• The major target is the myelin- The major target is the myelin- producing producing OLIGODENDROCYTESOLIGODENDROCYTES of the of the central nervous systemcentral nervous system

• An underlying autoimmune An underlying autoimmune mechanism may be involved as there mechanism may be involved as there are increased number of activated T are increased number of activated T lymphocytes in the CSF and increased lymphocytes in the CSF and increased immunoglobulin synthesis in CNSimmunoglobulin synthesis in CNS

PathologyPathology

It involves the triad of:It involves the triad of:

• Inflammation Inflammation

• Demyelination Demyelination

• Scarring (gliosis)Scarring (gliosis)

PathogenesisPathogenesis

• CNS inflammation in MS starts with entry of CNS inflammation in MS starts with entry of activated T lymphocytes through blood brain activated T lymphocytes through blood brain barrier barrier

• The resulting inflammatory cascade releases The resulting inflammatory cascade releases cytokines and initiates destruction of cytokines and initiates destruction of oligodendrocyte-myelin unit by macrophagesoligodendrocyte-myelin unit by macrophages

• Demyelination mostly occurs in Demyelination mostly occurs in periventricular regions of brain, optic nerves periventricular regions of brain, optic nerves and subpial regions of spinal cordand subpial regions of spinal cord

Precipitating factorsPrecipitating factors

• InfectionInfection

• TraumaTrauma

• SurgerySurgery

• Emotional and physical stressEmotional and physical stress

Common presentationsCommon presentations

• Optic neuritisOptic neuritis• Bilateral internuclear ophthalmoplegia is Bilateral internuclear ophthalmoplegia is

characteristic of MScharacteristic of MS• Relapsing and remmitting sensory symptomsRelapsing and remmitting sensory symptoms• Subacute painless spinal cord lesionSubacute painless spinal cord lesion• Acute brain stem syndromeAcute brain stem syndrome• Subacute loss of function of upper limb Subacute loss of function of upper limb

(dorsal column deficit)(dorsal column deficit)• 66thth cranial nerve palsy cranial nerve palsy

Other symptoms and Other symptoms and syndromessyndromes

•Afferent pupillary deficit and optic Afferent pupillary deficit and optic atrophy (previous optic neuritis)atrophy (previous optic neuritis)

•LhermitteLhermitte´s symptom ´s symptom (tingling in spine or limbs on neck (tingling in spine or limbs on neck

flexion)flexion)•Progressive non-compressive Progressive non-compressive

paraperesis paraperesis (Devic´s variant)(Devic´s variant)

Clinical featuresClinical features

• Uhthoff´s symptom; transient Uhthoff´s symptom; transient unilateral visual loss or blurring after unilateral visual loss or blurring after hot shower or exercisehot shower or exercise

• Partial Brown-Sequard syndromePartial Brown-Sequard syndrome

• Postural (rubral , Holmes ) tremorPostural (rubral , Holmes ) tremor

• Trigeminal neuralgiaTrigeminal neuralgia

• Recurrent facial palsyRecurrent facial palsy

Variants of MSVariants of MS

• Relapsing remitting (80%)Relapsing remitting (80%)

• Primary progressive (10-20%)Primary progressive (10-20%)

• Fulminant (<10%)Fulminant (<10%)

MarburgMarburg´s´s variant variant

• Secondary progressiveSecondary progressive

DiagnosisDiagnosis

A diagnosis of multiple sclerosis A diagnosis of multiple sclerosis requires the demonstration of requires the demonstration of lesions in more than one anatomical lesions in more than one anatomical site at more than one time for which site at more than one time for which there is no other explanationthere is no other explanation

INVESTIGATIONSINVESTIGATIONS

• No specific diagnostic test for No specific diagnostic test for multiple sclerosis.multiple sclerosis.

• Diagnosis is mainly clinical & tests Diagnosis is mainly clinical & tests are done to confirm the diagnosis are done to confirm the diagnosis and to exclude other conditions.and to exclude other conditions.

• Investigations can also predict Investigations can also predict prognosis after first episode.prognosis after first episode.

INVESTIGATIONS IN A PT INVESTIGATIONS IN A PT SUSPECTED TO HAVE MSSUSPECTED TO HAVE MS

• Exclude other structural disease & identify Exclude other structural disease & identify plaques of demyelinationplaques of demyelination::

MRI , MyelographyMRI , Myelography• Demonstrate other sites of involvement:Demonstrate other sites of involvement: MRI ,evoked potentialsMRI ,evoked potentials• Demonstrate inflammatory natureDemonstrate inflammatory nature:: CSF examination (oligoclonal bands)CSF examination (oligoclonal bands)• Exclude other conditions:Exclude other conditions: CXR, ACE levels, serum B12, antinuclear & CXR, ACE levels, serum B12, antinuclear &

antiphospholipid antibodies.antiphospholipid antibodies.

MRI BRAIN showing high signal MRI BRAIN showing high signal areasareas

Same MRI after few monthsSame MRI after few months

Multiple Sclerosis and Multiple Sclerosis and PregnancyPregnancy

ACUTE RELAPSEACUTE RELAPSE

Pulses of high-dose methylprednisolone Pulses of high-dose methylprednisolone either IV 1gm daily for 3 days or orally either IV 1gm daily for 3 days or orally 500mg daily for 5 days, shorten the 500mg daily for 5 days, shorten the duration of relapse but do not affect long-duration of relapse but do not affect long-term outcome. So long use of steroids term outcome. So long use of steroids should be avoided.should be avoided.

PREVENTING RELAPSESPREVENTING RELAPSES

• Immunosuppressive agents like Immunosuppressive agents like azathioprine reduces relapse rate.azathioprine reduces relapse rate.

• Subcutaneous or IM interferon beta-Subcutaneous or IM interferon beta-1a/b reduces the number of relapses 1a/b reduces the number of relapses by about 30% with a small effect on by about 30% with a small effect on longterm disabilitylongterm disability

• Glatiramer acetate has similar effects.Glatiramer acetate has similar effects.

Immune modulation therapyImmune modulation therapy

• Interferon betaInterferon beta• Glatiramer acetateGlatiramer acetate• AzathioprineAzathioprine• CyclophosphamideCyclophosphamide• MitoxantroneMitoxantrone• IV immunoglobulinsIV immunoglobulins• PlasmapharesisPlasmapharesis• Monoclonal antibodies to beta integrins (eg Monoclonal antibodies to beta integrins (eg

natalizumab)natalizumab)• Monoclonal antibodies to lymphocyte epitopes ( eg Monoclonal antibodies to lymphocyte epitopes ( eg

campath1-H)campath1-H)

NON SPECIFIC THERAPIESNON SPECIFIC THERAPIES

• Special diets including gluten free or Special diets including gluten free or linoleic acid supplements linoleic acid supplements

• Hyperbaric oxygenHyperbaric oxygen

are being used but of no provenare being used but of no proven

benefit.benefit.

COMPLICATIONSCOMPLICATIONS

• AtaxiaAtaxia

• SpasticitySpasticity

• DysaesthesiasDysaesthesias

• Bladder symptomsBladder symptoms

• ImpotenceImpotence

• FatigueFatigue

• DepressionDepression

PROGNOSISPROGNOSIS

• About 15% of those having an attack of About 15% of those having an attack of demyelination do not suffer any more demyelination do not suffer any more events.events.

• If optic neuritis is initial manifestation, If optic neuritis is initial manifestation, there may be no recurrence.there may be no recurrence.

• In relapsing remitting disease, there are In relapsing remitting disease, there are on average 1- 2 relapses every 2 years.on average 1- 2 relapses every 2 years.

• Approximately 5% of patients die within Approximately 5% of patients die within 5yrs of onset.5yrs of onset.

• 33% patients are dependant by 10yrs 33% patients are dependant by 10yrs rising to 50% after 15 yrs.rising to 50% after 15 yrs.