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How Can We Predict The Outcome
Of Multiple Sclerosis?
Amr Hassan
Associate Professor of Neurology
Cairo University
HETEROGENEITY
Pathological
subtypes
Clinical
presentation
Rates of
progression
Resonse to
DMT
2
3
Outcome of MS?
4
5
WHAT TO
FORECAST?
6
Sunny OR Stormy ?
7
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
Sunny OR Stormy ?
8
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
HOW TO
FORECAST?
9
10
A Biomarkers for Multiple Sclerosis:WHY ?
BIOMARKERS
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
A. GENETIC AND IMMUNOGENETIC
BIOMARKERS
BIOMARKERS
HLA
TOB-1
Apo lipoprotein-E
13
B. LABORATORY BIOMARKERS
BIOMARKERS
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
15
IV
VI
VII
VIII
III
I
16
BIOMARKERS
17
C. IMAGING BIOMARKERS
BIOMARKERS
BIOMARKERS
CLINICAL OCB MRI
18
Sunny OR Stormy ?
19
GOOD EPIDEIOLOGICAL
FACTORS
BAD
Female Sex Male
< 40 y Age > 40 y
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
Sunny OR Stormy ?
21
GOOD DISABILITY BAD
Long Time to EDSS 4-5 Short
GOOD MRI BAD
Low Lesion load High
Absent CEL Present
22
23
24
Sunny OR Stormy ?
25
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
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
27
Conversion of CIS to CDMS
CIS cohort study design.
Mar Tintore et al. Brain 2015;138:1863-1874
© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
All rights reserved. For Permissions, please email: journals.permissions@oup.com
Development of CDMS and an EDSS score of 3.0 according to the number of lesions on the
baseline MRI. Crosses: ≥10 lesions; triangles: 4–9 lesions; squares: 1–3 lesions; circles: 0
lesions.
Mar Tintore et al. Brain 2015;138:1863-1874
© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
All rights reserved. For Permissions, please email: journals.permissions@oup.com
30
Effect of baseline clinical, biological and MRI characteristics on the conversion to CDMS. (A)
CDMS univariate analysis; (B) CDMS multivariate analysis.
Mar Tintore et al. Brain 2015;138:1863-1874
© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
All rights reserved. For Permissions, please email: journals.permissions@oup.com
Effect of baseline clinical, biological and MRI characteristics on the risk of attaining an EDSS
score of 3.0.
Mar Tintore et al. Brain 2015;138:1863-1874
© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
All rights reserved. For Permissions, please email: journals.permissions@oup.com
33
Sunny OR Stormy ?
34
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
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
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
Aggressive MS
37
BREMSO
38
39
BREMSO
Sunny OR Stormy ?
40
• Conversion of CIS to CDMS
• Disease activity and progression
• Conversion of ADEM to CDMS
• Response to treatment
ADEM vs MS
Neurology. Sep 20, 2011; 77(12): 1143–1148.
ADEM vs MS
ADEM vs MS
ADEM MS
Restricted
forms of
ADEM
Recurrence
of ADEM
ADEM vs MS
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
Conversion of ADEM to CDMS
Conversion of ADEM to CDMS
THANK YOU

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Prediction of outcome of Multiple sclerosis

  • 1. How Can We Predict The Outcome Of Multiple Sclerosis? Amr Hassan Associate Professor of Neurology Cairo University
  • 4. 4
  • 5. 5
  • 7. Sunny OR Stormy ? 7 • Conversion of CIS to CDMS • Disease activity and progression • Conversion of ADEM to CDMS • Response to treatment
  • 8. Sunny OR Stormy ? 8 • Conversion of CIS to CDMS • Disease activity and progression • Conversion of ADEM to CDMS • Response to treatment
  • 10. 10 A Biomarkers for Multiple Sclerosis:WHY ? BIOMARKERS
  • 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
  • 22. 22
  • 23. 23
  • 24. 24
  • 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
  • 28. CIS cohort study design. Mar Tintore et al. Brain 2015;138:1863-1874 © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com
  • 29. Development of CDMS and an EDSS score of 3.0 according to the number of lesions on the baseline MRI. Crosses: ≥10 lesions; triangles: 4–9 lesions; squares: 1–3 lesions; circles: 0 lesions. Mar Tintore et al. Brain 2015;138:1863-1874 © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com
  • 30. 30
  • 31. Effect of baseline clinical, biological and MRI characteristics on the conversion to CDMS. (A) CDMS univariate analysis; (B) CDMS multivariate analysis. Mar Tintore et al. Brain 2015;138:1863-1874 © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com
  • 32. Effect of baseline clinical, biological and MRI characteristics on the risk of attaining an EDSS score of 3.0. Mar Tintore et al. Brain 2015;138:1863-1874 © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com
  • 33. 33
  • 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
  • 40. Sunny OR Stormy ? 40 • Conversion of CIS to CDMS • Disease activity and progression • Conversion of ADEM to CDMS • Response to treatment
  • 41. ADEM vs MS Neurology. Sep 20, 2011; 77(12): 1143–1148.
  • 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