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Conference · 19 August 2023

MRI findings in progressive multiple sclerosis

A clinical overview of what brain and spinal-cord MRI reveal about progression and treatment trials.

ICTRIMS · New Delhi, India

A web sketch of the deck’s central idea

Delivered: 19 August 2023
Event: ICTRIMS
Place: New Delhi, India
Format: Conference
Source deck: 35 slides

From the slides

Deck notes

This ICTRIMS lecture traced MRI findings in progressive multiple sclerosis from clinical phenotypes to quantitative measures of brain and spinal-cord change. It placed those measures in the context of treatment trials.

The question

What can MRI reveal about progression beyond the clinical labels used to describe multiple sclerosis?

Deck outline

The clinical description of progressive multiple sclerosis
Brain atrophy and percentage brain-volume change
Data-driven MRI subtypes
Evidence from treatment trials
Spinal-cord atrophy and disability
Clinical utility and targets for progression

Take-away

Brain and spinal-cord measures capture complementary aspects of progression, but their value rests on a clear connection to disability and treatment outcomes.

Original deck

Slide by slide

Read the 35-slide presentation in order, or use the index to jump.

Slide 01
MRI findings in Progressive Multiple Sclerosis
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Arman Eshaghi, MD, PhD
NIHR Advanced Fellow
UCL Queen Square Institute of Neurology
University College London
United Kingdom
Slide 02
Disclosures
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A.E has received research grants from the Medical Research Council (MRC), National Institute for Health and Social Care Research (NIHR), Innovate UK, Biogen, Merck, and Roche.
He serves as an advisory board member of Merck Serono and Bristol Myers Squib.
He is the founder and equity stake holder in Queen Square Analytics Limited.
He serves on the editorial board of Neurology (American Academy of Neurology).
Slide 03
Slide 3
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Slide 04
Outline
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Progressive MS
MRI signs
Quantitative MRI
Slide 05
Formes frustes: Charcot classification
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Spinal
Cerebral
Cerebrospinal
“Abortive”
Source: Multiple Sclerosis: The History of a Disease by Jack Murray
Slide 06
Marie classification
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Chronic course with intermittent attacks
Chronic remitting course
Increased improvement with apparent cure
Source: Multiple Sclerosis: The History of a Disease by Jack Murray
Slide 07
Marburg classification
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Acute
Rapidly progressive
Chronic progressive without symptoms
Typical remitting type with attacks and remissions
Stationary type
Source: Multiple Sclerosis: The History of a Disease by Jack Murray
Slide 08
George A. Schumacher
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Ian MacDonald
John Kurtzke
Donald Paty
Slide 09
Lublin et al., 1996, Neurology
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Relapsing remitting MS
Secondary progressive MS
Primary progressive MS
Speaker notes
- Start by: one of the main reasons for suboptimal treatment selection is ….
References
- Lublin et al., 1996, Neurology — PubMed
Slide 10
Lublin et al, 2014, Neurology
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References
- Lublin et al, 2014, Neurology — PubMed search
Slide 11
Progressive multiple sclerosis
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Similar pathology
Similar disease activity (adjusted for age)
Progression independent of activity
Slide 12
Scahil et al, JAMA Neurology, 2003
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References
- Scahil et al, JAMA Neurology, 2003 — PubMed search
Slide 13
Nicola De Stefano et al. J Neurol Neurosurg Psychiatry 2016;87:93-99
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References
- Nicola De Stefano et al. J Neurol Neurosurg Psychiatry 2016;87:93-99 — PubMed
Slide 14
Percentage brain volume change
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Slide 15
Kuhlmann et al, The Lancet Neurology, 2022
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References
- Kuhlmann et al, The Lancet Neurology, 2022 — PubMed
Slide 16
Data-driven MS types, Eshaghi et al, Nature Communication, 2021
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25%
32%
43%
References
- Data-driven MS types, Eshaghi et al, Nature Communication, 2021 — PubMed search
Slide 17
Montalban et al, 2017
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References
- Montalban et al, 2017 — PubMed search
Slide 18
Kappos et al, Lancet, 2018
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References
- Kappos et al, Lancet, 2018 — PubMed search
Slide 19
Slide 19
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Slide 20
Fox et al, 2018,
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Slide 21
Fisher et al, Annals of Neurology, 2008
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References
- Fisher et al, Annals of Neurology, 2008 — PubMed search
Slide 22
Eshaghi et al, 2018, Annals of Neurology
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References
- Eshaghi et al, 2018, Annals of Neurology — PubMed
Slide 23
MRI and clinical
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Clinical only
MRI only
Years
Hazard ratio:1.51
Hazard ratio: 1.31
Hazard ratio: 1.21
Slide 24
Azevedo et al, Annals of Neurology, 2018
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References
- Azevedo et al, Annals of Neurology, 2018 — PubMed search
Slide 25
Clinical utility ?
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Courtesy of Hugh Pemberton and Olivia Goodkin
Slide 26
Cagol et al, JAMA Neurology, 2022
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Lublin et al, Brain, 2022
Speaker notes
The effect size, expressed as mean difference in annual percentage cortical thickness change (MD-APC), is graphically displayed in different shades of blue for each of the Desikan-Killiany atlas25 regions presenting significant differences between groups after correction for multiple comparisons.
References
- Cagol et al, JAMA Neurology, 2022 — PubMed
- Lublin et al, Brain, 2022 — PubMed search
Slide 27
Spinal cord
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Slide 28
Tsagkas et al, Multiple Sclerosis Journal, 2018
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Valsasina et al, Radiology, 2018
Speaker notes
Hypointense lesions at T1-weighted imaging were observed in the cervical spinal cord of the majority of patients with MS and more widespread in progressive than in relapsing MS phenotypes. Both T1-weighted hypointense cord lesions and atrophy correlated with patient clinical disability
References
- Tsagkas et al, Multiple Sclerosis Journal, 2018 — PubMed
- Valsasina et al, Radiology, 2018 — PubMed
Slide 29
Rocca et al, Brain, 2018
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References
- Rocca et al, Brain, 2018 — PubMed search
Slide 30
Tur et al, Nature Reviews Neurology, 2018
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- Trials — Patients — Duration / (months) — Results / (treated vs. placebo)
- Frank et al. / MSJ 2002 — SPMS (n=6) RRMS (n=1) — 24 / weeks — RhIGF-1 (0.05 mg/kg twice a day) / Not reported (ns)
- Kalkers et al. / MSJ 2002 — PPMS (n=16) — 24 — Riluzole / -2.0% vs. -0.2% (NA)
- Leary et al. / Neurology 2003 — PPMS (n=50) — 24 — Interferon beta-1a (30μg and 60μg) / -0.5% vs -1.0% vs 0.3% after 12 months (ns) / -3.7% vs 1.5% vs -1.3% after 24 months (ns)
- Lin et al. / JNNP 2003 — RRMS (n=20) / SPMS (n=18) — 48 — Interferon beta-1a / -1.5% vs -2.8% after 12 months (ns) / -4.5% vs -5.7% after 48 months (ns)
- Montalban et al. / MSJ 2009 — PPMS (n=49) SPMS (n=24) — 24 — Interferon beta-1b / -1.6% vs -1.3% after 12 months (ns) / -0.9% vs -1.6% after 24 months (ns)
- Kapoor et al. / Lancet Neurol 2010 — SPMS (n=120) — 24 — Lamotrigine / -1.60% vs -1.26% after 24 months (ns)
- Yaldizli et al. / ECTRIMS 2015 — PPMS (n=823) — 24 — Fingolimod / -2.04% from baseline vs -2.44% after 24 months (ns)
References
Slide 31
Cawley et al, Multiple Sclerosis Journal, 2018
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Speaker notes
cord atrophy may not be a useful outcome measure in SPMS who have not showed a steady progression as the major cause of increasing disability in the preceding 2years history, have long disease duration and marked SC atrophy at study entry.
References
- Cawley et al, Multiple Sclerosis Journal, 2018 — PubMed search
Slide 32
Future
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Targeting progression
Automatic reading of atrophy (AI)
www.ms-pinpoint.com
Slide 33
Conclusion
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Evolving concept of “progression”
Signs of progressive disease
Future
Slide 34
Slide 34
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Email: a.eshaghi@ucl.ac.uk
Slide 35
Slide 35
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