T pnewlydiagnosed may_2012

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Multiple Sclerosis: disease, investigations, treatment Dr Trevor Pickersgill Consultant Neurologist UHW

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Transcript of T pnewlydiagnosed may_2012

Page 1: T pnewlydiagnosed may_2012

Multiple Sclerosis: disease, investigations, treatment

Dr Trevor Pickersgill

Consultant Neurologist UHW

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Summary History Pathology/causes Diagnosis and tests Range of disease Disease Modifying Treatments and

new treatments quackery

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Multiple Sclerosis is…..

A nasty illness…. A benign illness…… Rapid… Slow…. Treatable…. Untreatable….. Popular: Yahoo 33.4M hits

Google 67.5M hits

….a mixed bag - unpredictable

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What we really need is a medical…..

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St Lidwina of Schiedam 1380-1433

Debilitating disease Fell skating 16 Mobility Headaches Violent tooth pains Paraplegic 19 Disturbed vision Died 53

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Robert Carswell 1793-1857

Pathologist ‘strange lesions’ in

spinal cord

Jean Cruveilhier - parisian anatomist

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Jean-Martin Charcot 1825-1893

Salpetriere La sclerose en plaque First to make

clinicopathological links 40 yrs after lesions

described Charcot’s (housekeeper’s)

Triad: Double vision Ataxia/unsteady Dysarthria/slurred

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What Is MS? Inflammatory,

Demyelinating Disease

Specific to the Central Nervous System

Commonest cause of chronic neurological disability in young adults in the UK

20-40 yrs RR------->SP

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What causes Multiple Sclerosis?

Chance Genes


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= Redness

= heat

= pain

= swelling

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Cardinal feature: brain/spine inflammation

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CNS Inflammation Blood-brain barrier

breached T Cell (white blood cell -

fight infection) sticks to lining

Migrates in Attracts more

inflammation cells and cytokines (attraction chemicals) produced

Inflammation causes demyelination

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Demyelinating lesions in multiple sclerosis

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Disturbs nerve messages

Slows conduction May cause block Interrupts normal

function of nerves May be silent I.e.

cause no problems

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Putative Triggers

Virus/bacterial infection EBV/glandular fever?

Cross reactivity of virus coat proteins

Other environmental triggers Susceptible person ….all may trigger an

“autoimmune” process

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An immune disease

White cell activation Complement (destroys cells)

activation Low level of immune activity

normally - CNS ‘naïve’ antibodies - various or ‘oligo’-

clonal in CSF F>M

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Who Does MS Affect? Incidence 1 per 800 adult population 150/100,000 SE Wales (90-200 UK) 85,000 people in the UK Female to male 3:2

Age distribution by sex

Age group

Patient Nos


0-14 15-24 25-34 35-44 45-54 55-64 65-74 >75



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What about my children?

1 parent/sib/child: 2-4% 97% risk of not getting MS Risk is over lifetime - so

depends on their age If you are 50 you have lived

through most of the risk 1 non-immediate relative

Risk same as population

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Crucial is clinical story - dissemination in time and space…. I.e. multiple sclerosis

Poser criteria 1983 Definite Probable Possible Lab-supported/clinical

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Diagnosis 2 - exclude other stuff

Lupus Sarcoid Strokes Functional illness e.g. anxiety Infection

How? - blood tests, chest Xray, MRI interpretation, lumbar puncture, symptoms

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Is it MS? - case 1

F Age 14/15 tingling fingers Fatigue and weakness Ix KL and KCH

Age 21 Numb feet and fingers, fatigue UCC netball team Patch of sens forearms VEP normal, OB+

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MRI 2000MRI 2005

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1 attack 1 clinical lesion No paraclinical evidence of

other lesions - MRI/VEP CSF + - told she had MS

‘single’ myelitis - not MS Strictly not ‘clinically isolated


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Multiple sclerosis: Brain MRI - changing lesions

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McDonald Criteria

Basically MRI can now clinch the diagnosis alone

Even in context of single episode (CIS) >3 months interval New lesions appearing or any dye enhancing =

Dissemination in Time Dissemination in space criteria now defined Mixture of old and new lesions on single

enhanced scan

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Case 2 - is it MS? 26F 20th August 2004 10d h/o L arm feeling heavy, foot

dragging, bladder sensation Clumsy hand - typing Vision normal No headache 4 wks previously viral illness

with N+V, abdo pain Swollen optic discs

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Florid WM lesions No infratentorial CSF acellular Severe headache Resolved with IVMP 31/8/04 no signs DIAGNOSIS = first

episode CIS

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Story continued

21/9/04 - foggy vision R eye Less than 1 month separation 16/17 Ishihara L nil else

Resolved over 10d until 1/11/04 R periorbital pain 3/11/04 VA 1/60 Rx IVMP 16/11/04 HM - large scotoma

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MRI Dec 2004

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Is it MS? ….yes

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Dynamic disease

Constant lesion formation

Not all lesions cause symptoms (10%?)

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Lumbar Puncture

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CSF/lumbar puncture analysis

Raised WBC sometimes

Protein normal/marginal

Characteristic IgG pattern

‘Band negative’ MS

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“Types” of MS: are you a lumper or a splitter?

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Types of MS

Benign retrospective diagnosis

relapsing/remitting(RR) 80% of those initially diagnosed will follow this disease course

secondary progressive (SP) 50-60% of PwMS will have this type

primary progressive (PP) 10-20% of PwMS. No relapses at onset, progressive disability.

Spinal disease. More severe.

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Mean time to EDSS 6.0 Mean time to EDSS 6.0 -18yrs-18yrs

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New neurological symptoms and/or signs persisting for more than 24h not in the context of infection

Many mild, bothersome, irritating only

Some more severe - may need treatment

Some studies as low as 0.5/yr

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Relapse treatment

Steroid tablets (Intravenous steroids) Wait and see Do not affect outcome

Outpatient Inpatient Rapid Access Clinic UHW

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Disease Modifying Treatments

Licensed c.1999 NICE appraisal Modest usefulness 30% reduction

relapses ß-ifn:

Avonex Rebif Betaferon

Copolymer-1 Side effects

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Look for documentary evidence of new neurological deficit

>2 ‘disabling’ attacks 2yrs Assessment quite subjective

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Eligibility 2

2+ disabling relapses /2yrs Ambulant 10m+ No/minimal background

progression No contraindications Willing to inject!

30% choose to withdraw

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Newer Treatments:Campath-1H/alemtuzumab

Anti-T cell monoclonal antibody Not licensed for MS (yet) Treatment for leukaemia 80+ pts treated South Wales

Relapses reduce 90% study early disease v high dose ß-ifn -

55% better than IFN Side effects - long term Single treatment annually - drip once

a year

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Newer Treatments - Tysabri/natalizumab

Reduces adhesion molecules in T cell migration

Prevents BBB breakdown Early studies promising MRI

data 2yr RCT early RRMS 68% reduction relapses Licensed NHS: ‘highly active’ Monthly drip - 15pts Cardiff

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Cell migration

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PML risk JC virus 40-80% of us have it Sits dormant in brain Reactivated when ‘normal’ immune system is

damaged (HIV) PML - untreatable - can be mild or fatal Peak after 2 yrs Risk 1:800 overall. Can test for virus

If negative 1:10,000 If positive, and had other drugs 1:100

150+ cases in 100,000 patients

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New Drugs - oral [Cladribine] Fingolimod/Gilenya

Daily treatment Heart and skin and eye problems Licensed recently FDA USA Licensed EU April 2011 50% reduction relapses Recently approved NICE

Eligibility Interferon failure 1+ relapses 1yr and active MRI

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Gilenya Once a day tablet £19,000/yr NICE appraisal - rejected - under

appeal - now approved First dose - risk of heart block ‘rapidly evolving severe MS’ or

interferon failure MS. Macular oedema/blood

pressure/infections 3500 Germany

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Fampridine Oral tablet Improves walking efficiency

Speed Stride Fatigue

Works in 25% of pts Mechanism unsure £360/month - recently licensed Not yet approved NHS - company

hasn’t applied!

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Vitamin D

Small studies show MASSIVE doses may reduce relapses

UK population deficient Month of birth studies - higher

risk of MS if born spring 1000 v 14,000 units/day Risks...pregnancy, heart

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On the horizon.....

Teriflunomide Laquinimod Baclivuzumab Rituximab Daclizumab BG12

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CCSVI....the latest wonder cure Italian doctor New technique

measuring jugular vein flow

‘100%’ accurate Experimented on his

wife Dozens of private

clinics Few large studies -


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CCSVI - facts Hugely conflicting results ‘too good to be true’ MS is an immune disease.....FACT! Sluggish blood flow could not cause

this.... But might be an after-effect Lots of money to be made.....treating

the rich and the desperate...

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And then there was…. Goats’ serum LDN Omega 3 Vit D??? Sativex -


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Thank You


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