Accelerated Cord Atrophy Precedes Conversion to Secondary - - PowerPoint PPT Presentation

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

Background

• Understanding of progressive disease major challenge in

multiple sclerosis (MS) research

• MRI measures might provide useful surrogates of disease

progression and disability

• Among all radiographic measures, spinal cord area shows the

strongest correlations with MS disability and discriminates progressive from relapsing-remitting (RR) disease subtypes.

Study Design

• Participants:

– 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

• bservation period (RR→RR)

– 54 age- and sex-matched healthy controls at study baseline (CTRL)

• Main Outcomes

Baseline and annual change during the pre-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

Spinal cord area measurement at C1 level

• n T1-w brain images

Results: Baseline Characteristics

Characteristics Level CTRL (n=54) RR→RR (n=54) RR→SP (n=54) p

Baseline Sex F 32 (59) 32 (59) 32 (59) M 22 (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) 0·002 Conversion Age** F

• 54 (12)

0·208 M

• 52 (14)

Disease Duration** F

• 19 (11)

0·096 M

• 15 (9)

Treatment† Naïve

• 10 (19)

5 (9) 0·104 Low

• 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.

Annualized cord atrophy rates discriminate between the matched groups pre-conversion

*using a mixed-effects model with adjustment for age and sex

Time from MRI Baseline (years)

2 4 6 8 10 12 14

C1A (mm2)

80 85 90 95 100 105 110

Group RR RR RR SP

RR→RR group: -0.74%/year RR→SP group: -2.15%/year Measureable up to 4 years before conversion to SPMS No effect of

• Relapse rate
• Disease duration
• New/enlarging lesions
• Disease-modifying treatments
• Slowly enlarging lesions

p<0.0001*

Baseline Brain Volumes are lower in patients, but do not differentiate between the two patient groups

1420 1430 1440 1450 1460 1470 1480 1490 1500 1510 WBV 730 735 740 745 750 755 760 765 770 775 GMV 690 700 710 720 730 740 WMV 590 595 600 605 610 615 620 625 630 cGMV 15 20 25 30 VV 19.5 20.0 20.5 21.0 21.5 22.0 22.5 23.0 Thalamus 8.5 9.0 9.5 10.0 Caudate 12.0 12.5 13.0 13.5 14.0 Putamen Brain Volumes (cc)

*** *** ** ** *** *** ** ** *** ** *** *** * *** *** *** CTRL RR RR RR SP

Based on least squares regression analyses, adjusted for age and sex

* p≤ 0·05, ** p≤ 0·005, ** p≤ 0·0001

Conclusions

• Cervical 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 not

• Could be useful

– To study the role of genetic, epidemiologic and immune variables on MS – To measure the long-term impact of treatment in clinical trials – For early stratification of patients at risk for severe disability to guide individualized treatment decisions – Retrospective analysis of large number of legacy brain scans worldwide acquired in clinical trials and observational MS cohort studies