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Dr Guadagno: MS Senory Symptoms
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
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
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
19.
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….
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.
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
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?
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?
In the upper row on the left, CT shows lesions fewer lesions and reveals a smaller affected area than MRI. In the middle column a large, hypointense lesion can be seen in the region of the right occipital lobe (angular gyrus and intraparietal sulcus) in a T1 weighted image. On the right, a T2 weighted image reveals the typical, multifocal affection of PML with additional lesions in the white matter of the left frontal lobe and the white matter of the tempoaral and occipital lobe. Note sparing of grey matter. In the lower row, CT shows contrast enhancement in the right cerebral peduncles as does MRI with Gadolineum in the middle column. On the right, T2-weighted imaging, an additional hyperintense lesion can be seen in the white matter in the inferior posterior temporal gyrus on the right.
