Precedes Conversion to Secondary Progressive Disease in Relapsing Multiple Sclerosis Antje Bischof MD Multiple Sclerosis Research Group University of California San Francisco Background U ID: 784727
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Slide1
Accelerated Cord Atrophy Precedes Conversion to Secondary Progressive Disease in Relapsing Multiple Sclerosis
Antje Bischof, MD
Multiple Sclerosis Research Group
University of California, San Francisco
Slide2BackgroundUnderstanding of progressive
disease
major challenge in multiple sclerosis (MS)
research
MRI
measures might provide useful surrogates of disease progression and
disability
A
mong
all radiographic measures, spinal cord area shows the strongest correlations with MS disability and discriminates progressive from relapsing-remitting (RR) disease subtypes.
Slide3Study DesignParticipants:
54
RRMS patients
who converted
to SPMS during the 12-year observation
period
(RR
SP
)
54
matching RRMS patients (sex, age, disease duration, EDSS) who remained RRMS during the observation
period (RR
RR)
54 age- and sex-matched healthy controls at study baseline (CTRL)
Main Outcomes
Baseline
and
annual change during
the p
re
-
conversion period)
:
Spinal
cord area at C1 level
Brain T1, T2 lesion load
Brain volumes
:
Global: Regional:
Whole
brain - Thalamus
White
matter - Caudate nucleus
Gray
matter - Putamen
Ventricular Volume
Slide4Spinal cord area
measurement at
C1 level
on
T1-w brain images
Slide5Results: Baseline Characteristics
Characteristics
Level
CTRL
(n=54)
RR
RR
(n=54)RRSP (n=54)pBaseline SexF32 (59)32 (59)32 (59) M22 (41)22 (41)22 (41) Age*44 (14)49 (15·3)47 (14·5)0·191 Disease Duration** -10 (14·3)12 (14·0)0·995 EDSS**-1·5 (1·5)2·5 (1·5) 0·0002 MSSS** -1·5 (2·5)2·6 (3·5)0·002Conversion Age**F--54 (12)0·208M--52 (14) Disease Duration**F--19 (11)0·096M--15 (9) Treatment†Naïve-10 (19)5 (9)0·104Low-35 (65)35 (65) Intermediate-3 (6)4 (7) High-6 (11)10 (19)
Differences were analysed using
*
Kruskal
-Wallis,
**
Wilcoxon rank sum, or
†
Chi-square tests.
Slide6Annualized cord atrophy rates discriminate between the matched groups pre-conversion
*
using a mixed-effects model with adjustment for age and
sex
RR
RR group: -0.74%/year
RR
SP group: -2.15%/yearMeasureable up to 4 years before conversion to SPMSNo effect of Relapse rateDisease durationNew/enlarging lesionsDisease-modifying treatmentsSlowly enlarging lesionsp<0.0001*
Slide7Baseline Brain Volumes are lower in patients, but do not differentiate between the two patient groups
Based on least squares regression analyses, adjusted for age and sex
*
p
≤ 0·05,
*
*
p
≤ 0·005, ** p≤ 0·0001
Slide8ConclusionsCervical cord atrophy (C1 level), obtained from routine brain MRI, is a strong indicator of impending conversion to
SPMS
Brain measures, including
T1 and T2 lesion volumes,
and
regional and global brain volumes at baseline
and over time
do not discriminate
course compared to those who did notCould be useful To study the role of genetic, epidemiologic and immune variables on MSTo measure the long-term impact of treatment in clinical trialsFor early stratification of patients at risk for severe disability to guide individualized treatment decisionsRetrospective analysis of large number of legacy brain scans worldwide acquired in clinical trials and observational MS cohort studies