Prediction of outcome of Multiple sclerosis
An understanding of the natural history of multiple sclerosis(MS) in a patient is important to begin proper treatment at the correct time, especially when there is a high risk for poor prognosis. Factors that predict unfavorable prognosis are a primary or secondary progressive course, older age at disease onset, short interval between first and second attacks, initial cerebellar or pyramidal symptoms, a large number of functional systems involved at onset, moderate to severe disability within the first 2 years, and the presence of typical plaques or greater lesion volume shown by magnetic resonance imaging results during the first 5 years. However, there are no established laboratory tests able to predict long-term prognosis.
11. 11
GENETIC/IMMUNOGENETIC:
• Biomarkers specified via genomics and immunogenetic
techniques.
LABORATORY:
• All other biomarkers that can be measured in body
fluids.
IMAGING:
• Biomarkers provided by imaging techniques.
BIOMARKERS
12. 12
A. GENETIC AND IMMUNOGENETIC
BIOMARKERS
BIOMARKERS
HLA
TOB-1
Apo lipoprotein-E
14. 14
I. Biomarkers of Immunological Activation
II. Biomarkers of Neuroprotection
III. Biomarkers of BBB disruption
IV. Biomarkers of demyelination
V. Biomarkers of Oxidative Stress
VI. Biomarkers of Axonal Damage
VII. Biomarkers of Glial Activation Dysfunction
VIII. Biomarkers of Remyelination Repair
IX. Biomarkers of Therapeutic Response
X. Prognostic Biomarkers
XI. Emering biomarkers
B. Laboratory Biomarkers
19. Sunny OR Stormy ?
19
GOOD EPIDEIOLOGICAL
FACTORS
BAD
Female Sex Male
< 40 y Age > 40 y
20. Sunny OR Stormy ?
20
GOOD RELAPSES BAD
Mild, monofocal 1st relapse Severe , multifocal
Sensory, ON Clinical presentation Motor, cerebellar
Full recovery Response to ttt Residual
Long Time to 2nd relapse Short
Low Relapse rate High
21. Sunny OR Stormy ?
21
GOOD DISABILITY BAD
Long Time to EDSS 4-5 Short
GOOD MRI BAD
Low Lesion load High
Absent CEL Present
25. Sunny OR Stormy ?
25
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
26. MRI brain and cervical cord (1)
with Gd
Abnormal
[conversion rate 80%] (2)
Wait till
CDMS
DMT
Normal
[conversion rate 20%] (2)
Follow up
26
Conversion of CIS to CDMS
34. Sunny OR Stormy ?
34
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
35. Long-term follow-up of initially benign multiple
sclerosis patients: results from the Swedish
multiple sclerosis register
A. Manouchehrinia ,O. Beiki ,R. Ramanujam ,A. Kavaliunas ,A. Glaser ,J.
Hillert
• Results: 2,185 (19.2%) patients were initially benign. Benign patients were more
likely to be female (76% vs. 70%, P < 0.001), have relapsing onset MS (98% vs.
89%, P < 0.001) and be younger at the onset (29.1 vs. 34.4 years, P < 0.001). The
first recorded EDSS score was an average 1.5 score lower (3.3 vs. 1.8) in benign
patients despite being recorded almost 7 years later than non-benign patients. The
Kaplan-Meier estimate of median age at EDSS scores 4.0 and 6.0 were 75.1 years
(95%CI: 70.9 to 77.7) and 79.3 years (95%CI: 79.1 to NA) in benign cases compared
with 52.8 years (95%CI: 51.8 to 53.4) and 57.8 years (95%CI: 57.1 to 58.4) in non-
benign cases. 28% of benign MS patients converted to SPMS at a median age of
66.5 (95%CI: 64.4 to 69.3) compared with 39% of non-benign cases who did so
at as median age of 55.3 (95%CI: 54.6 to 55.9).
35
36. Is it possible to predict benign multiple sclerosis?
A. Sartori ,M. Abdoli ,M.S. Freedman
• Objectives: To compare clinical and paraclinical characteristics of benign MS patients defined as
EDSS score ≤3, 10 years from disease onset with those who still fulfilled that definition vs. being
NLB at 20 years from disease onset.
Methods and patients: A retrospective study of patients at the Ottawa Hospital MS Clinic was
performed, looking for patients with the following inclusion criteria: clinically definite MS (not CIS);
EDSS score ≤3 at 10 years from onset of first symptoms; disease onset from December 1983 -
December 1993; clinical assessments performed at 10±1 and 20±1 years from onset of MS
symptoms.
Results: We found 175 patients fulfilling the inclusion criteria. 20 years from disease onset,
66.3% of patients still remained benign. Considering patients with EDSS score ≤2 or ≤1 at 10
years, the percentage remaining benign at 20 years increased to 71.9% and 81.6%, respectively.
In a univariate analysis, female sex, EDSS score ≤1 at 10 years and a pure sensory onset
represented the most favourable prognostic factors; EDSS score >2 and a pure motor symptom at
onset were associated with the greatest chance of being NLB at 20 years. There were
significantly more patients (p=0.033) treated with disease modifying drugs (DMD) in the NLB
group. In a logistic regression analysis EDSS ≤1 at 10 years was able to predict a benign course
at 20 years with better than 80% specificity.
Discussion and conclusions: We found a higher percentage of benign patients at 20 years
compared to previous studies, possibly due to a higher percentage of patients treated with DMD
in our population. A multivariate analysis did not find any early clinical variable that could predict a
benign course at 20 years. However, EDSS ≤2 at 10 years had a better predictive value than
EDSS score ≤3 at 10 years, which was neither sensitive nor specific for predicting continuing to
be benign at 20 years. Most patients acquiring early disability (>2) before 10 years are very
unlikely to remain benign. We propose that a better definition of benign use stricter EDSS cut-offs
(≤2 or even ≤1) at 10 years, in order to enhance the specificity.
36
46. Flow chart/decision tree for the diagnosis of acute disseminated enceph-alomyelitis (ADEM), recurrent ADEM, multiphasic ADEM,
and pediatric multiple sclerosis.Amna Al-Futaisi. Oman Med J. 2007 October;22(3):11-15.
ADEM
SUBSEQUENT
RELAPSE
CIS
Subsequent Episode of CNS
Demyellnadng Event (NOT
ADEM)
New MRI finding and positive
MRI ≥ months after first
event
Recurrent
ADEM
Multiphasic
ADEM
ADEM MS
Repeat with
Idencial
features
Repeat with
new features
and change in
mental status
<10 Yrs Old ≥ 10 Yrs old
Repeat ≤ 3
months or
within 1 month
of steroids
ADEM vs MS