Talk to patients given regularly at our

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

2. Overview
Summary
History
Pathology/causes
Diagnosis and tests
Range of disease
Disease Modifying Treatments and
new treatments
quackery

3. 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

4. What we really need is a
medical…..

5. St Lidwina of Schiedam
1380-1433
Debilitating disease
Fell skating 16
Mobility
Headaches
Violent tooth pains
Paraplegic 19
Disturbed vision
Died 53

6. Robert Carswell 1793-1857
Pathologist
‘strange lesions’ in
spinal cord
Jean Cruveilhier -
parisian anatomist

7. 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

8. 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

9. What causes Multiple
Sclerosis?
Chance Genes
Environment

10. Inflammation
Rubor = Redness
Calor = heat
= pain
Dolor
Tumor = swelling

11. Cardinal feature:
brain/spine inflammation

12. 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

13. Demyelinating lesions in
multiple sclerosis

14. Demyelination
Disturbs nerve
messages
Slows conduction
May cause block
Interrupts normal
function of nerves
May be silent I.e.
cause no problems

15. 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

16. 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

18. 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
80
70
60
50 male
40
30 female
Patient Nos
20
10
0
0-14 15-24 25-34 35-44 45-54 55-64 65-74 >75
Age group

19. 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

20. Diagnosis
Crucial is clinical story -
dissemination in time and
space…. I.e. multiple sclerosis
Poser criteria 1983
Definite
Probable
Possible
Lab-supported/clinical

21. Diagnosis 2 - exclude
other stuff
Lupus
Sarcoid
Strokes
Functional illness e.g. anxiety
Infection
How? - blood tests, chest Xray,
MRI interpretation, lumbar
puncture, symptoms

22. 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+

23. MRI 2000 MRI 2005

24. Diagnosis?
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
syndrome’

25. Multiple sclerosis: Brain MRI -
changing lesions
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26. 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

27. 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

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

29. 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

30. MRI Dec 2004

31. Is it MS? ….yes

33. Dynamic disease
Constant lesion formation
Not all lesions cause symptoms (10%?)
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34. Lumbar Puncture

35. CSF/lumbar puncture
analysis
Raised WBC
sometimes
Protein
normal/marginal
Characteristic IgG
pattern
‘Band negative’ MS

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

38. 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.

39. Prognosis
Mean time to EDSS 6.0
-18yrs

40. Relapses
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

41. Relapse treatment
Steroid tablets
(Intravenous steroids)
Wait and see
Do not affect outcome
Outpatient
Inpatient
Rapid Access Clinic UHW

42. Disease Modifying
Treatments
Licensed c.1999
NICE appraisal
Modest usefulness
30% reduction
relapses
ß-ifn:
Avonex
Rebif
Betaferon
Copolymer-1
Side effects

43. Eligibility:
Look for documentary evidence
of new neurological deficit
>2 ‘disabling’ attacks 2yrs
Assessment quite subjective

44. Eligibility 2
2+ disabling relapses /2yrs
Ambulant 10m+
No/minimal background
progression
No contraindications
Willing to inject!
30% choose to withdraw

45. 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

46. 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

47. Cell migration

48. 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

49. 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

50. 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

51. 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!

52. 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

53. On the horizon.....
Teriflunomide
Laquinimod
Baclivuzumab
Rituximab
Daclizumab
BG12

55. 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 -
deaths?

56. 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...

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

58. Thank You
Acknowledgments:
NI team UHW
MS Society Cymru
All attendees today