This document provides information about multiple sclerosis (MS) and sensory symptoms that may indicate MS. It begins with statistics on the prevalence of MS, noting it is most common in young people and more prevalent in women. Typical presentations of MS include transverse myelitis, brainstem syndromes, optic neuritis, and paroxysmal symptoms. Common sensory symptoms of MS are described, such as ascending numbness in the feet or bilateral hand numbness. The document outlines current disease-modifying therapies for MS including interferon-beta medications and glatiramer acetate. It discusses new oral and infusion therapies in development like fingolimod, dimethyl fumarate, and alemtuzumab.

1. “Have I got MS?”
- advice on sensory symptoms
Joe Guadagno
Royal Victoria Infirmary
Newcastle upon Tyne

2. Outline
 Brief reminder of MS:
 Incidence, dermographics
 Usual presenting features
 Helpful basic tips?
 Temporal evolution of sensory symptoms
 What are the typical sensory symptoms of MS?
 What is not typical for MS……
 Other neurological conditions with sensory
symptoms
 New DMT’s – brief update!

3. Statistics
 Commonest cause of
acquired neurological
disability in young people
 Prevalence in UK (~1990s):
 NI 168/100 000
• (?230 2006)
 Tayside 184/100 000
 NE England ?150/100 000
(1:650)
 F:M 3:1

4. What is MS?
 Clinical diagnosis
 Loosest definition:
1. At least 2 episodes of CNS
dysfunction
(relapses/attacks/exacerbations)
2. ‘disseminated in time and space’
3. not explained by something else

5. Diagnostic criteria
(revised McDonald 2010)

6. MRI

7. relapsing/ remitting primary progressive
Patterns of MS
secondary progressive
85% 15%

8. relapsing/ remitting primary progressive
Patterns of MS
secondary progressive
85% 15%
(‘benign’)
5%

9. Aetiology
 genetic
1 in 6 cases have affected relative
1 in 650 general population
1 in 50 chance if one affected parent
but only 30% concordance in identical
twins

10. Aetiology: environmental
Geographical variation

11. UV exposure?

12. Genetic and environmental?
 migration studies
– environmental hit acquired in childhood (15yr)
– repeated or prolonged exposure
– latency
 infections? EBV?
 vitamin D/sunlight?
 Hygiene Hypothesis – ‘idle immune system’
 - acquired disease in a genetically
susceptible individual: cumulative insults?

13. What is MS?
inflammation degeneration

14. What is MS?
inflammation degeneration

15. Common presentations
(relapses)
 transverse myelitis
 brainstem syndromes
 optic neuritis
 paroxysmal symptoms

16.  The duration of the attack should
be longer than 24 hours!
 And not in the context of an
infection (pseudorelapse)

17.  Helpful tip (when addressing sensory
symptoms)
– remember the temporal evolution of
relapses

18. Typical ON - Recovery
VisualFunction
1 to 2/52 3 to 5/52

20. What are the typical sensory
symptoms of MS?
(Nb around 35% of presenting symptoms are sensory
(Olec 2005 and Paty et al 1994))
• ascending numbness starting in the feet;
• bilateral hand numbness;
• Hemiparesthesia (rare thalamic presentation);
• dysesthesia in the whole of one limb (or non
dermatomal);
• “sunburn” feeling or “itch” in a non-dermatomal
patch
• MS ‘Hug’
• Facial sensory disturbance and typical TN
• Lhermittes phenomena

21.  Whole body numbness or parasthesia
 Transient flitting sensory disturbances
(parasthesia or numbness) lasting minutes
to hours
 uncomplicated Bell’s palsy
 fatigue as isolated or predominant
symptom
 chronic dizziness/ light-headedness
 “weakness” in setting of musculoskeletal
pain/tenderness
 atypical facial pain
What is not MS….

22. Sensory symptoms from other
neurological disorders (and should
be referred……)

23. Keep in mind a
little bit of
neuroanatomy…
………

24. Radiculopathies (pain!)

25. Entrapment
neuropathies
CTS
Ulnar
Lateral Cutaneous Nerve
(meralgia parasthetica)
Common peroneal Nerve

27. Management of relapses
 Nothing (especially sensory)
 Steroids
Oral 500mg methlypred for 5 days
IV 1000mg for 3 days

28. Disease modifying therapy
- First line
 Five licensed therapies
 Interferon-β
• Avonex
• Betaferon
• Extavia
• Rebif
 Copaxone
 Prescribed under ABN
guidelines

29. † Measured as the total over 2 years
‡ The Avonex trial required a sustained progression for 6 months; the Rebif trial, for 3 months; and the Copaxone trial, for 3 months
First line DMTs
Summary of results from pivotal phase 3 trials
Agent Dosage Reduction in
relapses, % †
Relapse-free
patients, % †
Interferon beta-1b
(Betaferon)
8 mIU (250 µg)
SC every other
day
34 31
Interferon beta-1a
(Avonex)
30 µg
IM once weekly 32 38
Interferon beta-1a
(Rebif)
22 µg
SC 3 times
weekly
29 27
44 µg
SC 3 times
weekly
32 32
Glatiramer acetate
(Copaxone)
20 mg
SC once daily 29 34
Adapted from Galetta S, et al. Arch Int Med 2002; 162; 2161-2169

30. Beyond one third relapse
reduction…..
New Disease
Modifying therapies.

31. Natalizumab (Tysabri)
- A humanised monoclonal antibody

32. Leukocyte entry to the
nervous system
blood
brain
firm
adhesion
rolling slow
rolling
capture diapedesis
chemokines
(incl. MCP-1/CCR-2)
inflammation
chemokines
selectins integrins
(incl. VLA-4)
migration

33. Natalizumab (Tysabri)
blood
brain
firm
adhesion
rolling slow
rolling
capture diapedesis
inflammation
selectins integrins
(incl. VLA-4)

34. Natalizumab: good things
AFFIRM Highly Active* 1
(n= 148 for TYSABRI, 61 for PBO)
81%
64%
reduction in annualised relapse rate vs.
placebo over 2 years (p < 0.001)
reduction in the risk of disability
progression, sustained for 24 weeks, as
assessed over 2 years (p =0.008)
Patients With ≥2 Relapses in Prior Year and ≥1 Gd+ Lesion At
Baseline

35. 2010 2011

36. Progressive Multifocal
Leukoencephalopathy (JC virus)

37. New Oral therapies!
Fingolimod (Gilenya)
“FDA Panel Unanimously Recommends Approval of First Oral MS Drug”
A Food and Drug Administration advisory panel on Thursday unanimously
recommended approval of the first drug for multiple sclerosis (MS) that can be taken
orally.

38. FREEDOMS:
Annualised relapse rate (ARR) at 2 years (primary endpoint)
Kappos et al, N Engl J Med 2010; 362: 387–410; Cohen et al, Poster P901 presented at ENS 2011; Francis and Haering, April 2011; data on file
Negative binomial regression model adjusted for treatment group, country, number of relapses in previous two years and baseline EDSS. Bars represent the 95%
CI; ARR, annualised relapse rate; DMT, disease-modifying treatment. Based on efficacy and safety profile, fingolimod 0.5 mg/day is the only approved dose for
the treatment of MS
0
0.18
(0.15–0.22)
0.40
(0.34–0.47)
0.1
0.2
0.3
0.4
ARR
Placebo
(n=418)
Fingolimod 0.5 mg
(n=425)
-54%
p<0.001

39. Possibly not so good things
about fingolimod
 completely new class of drug (SIP1
inhibitor)
 slows heart on first dose
 Macular oedema risk
 2 deaths
herpes encephalitis
Disseminated chicken pox
no long term safety data
Teratogenicity?

40. 31% reduction

41.  inhibits dihydroorotate dehydrogenase
(DHODH),
- a mitochondrial enzyme involved in de
novo pyrimidine synthesis (needed for the
proliferation of activated lymphocytes).
 LFT’s! – needs 2 weekly bloods for 6 months!
 Hair thinning/alopecia
 Stays in system a long time (up to 2 years)
so pregnancy effects?

42. Others dues soon….!
 Tecfidera (dimethy fumarate - oral)
 Lemtrada (Alemtuzemab – infusion)