Pediatric MS Poster Presentation

P1070 - Age at disease onset influences grey matter and white matter integrity in MS (ID 1070)

Speakers
  • R. Bonacchi
Authors
  • A. Meani
  • E. Pagani
  • M. Filippi
  • M. Rocca
Presentation Number
P1070
Presentation Topic
Pediatric MS

Abstract

Background

Natural history studies demonstrated clinical phenotype and course of multiple sclerosis (MS) are age-dependent. The comparison of pediatric (POMS) vs adult onset (AOMS) MS patients is a useful model for studying the effects of age on MS pathophysiology.

Objectives

To determine whether age of disease onset influences the extent, distribution and trajectories of development of brain grey matter volume (GMV) and white matter (WM) microstructural abnormalities in adult MS patients.

Methods

Sixty-seven POMS (40 females; age 30±9, range 18–53) and 143 sex- and disease duration-matched AOMS (85 females; age 46±11, range 20 – 70) patients, together with 208 age- and sex-matched healthy controls (HC) (120 females; age 37±14, range 18–70), underwent neurological examination (with Expanded Disability Status Scale [EDSS] scoring) and MRI acquisition on a 3T scanner, including dual echo, 3D T1-weighted, and diffusion-weighted sequences. T2-lesion volumes, GMV and WM fractional anisotropy (FA) were derived and standardized based on distribution in HC, to remove the effects of age and sex. Linear models were used to study associations with disease duration in POMS and AOMS patients. Time to reach clinical and radiological milestones was assessed with the product-limit approach.

Results

At disease duration=1year, GMV and WM FA were not abnormal in POMS, while they were already compromised in AOMS patients (p ranging from 0.04 to <0.001) compared to HC. Significant interaction of age at onset (POMS vs AOMS) into the association with disease duration was found for GMV (p=0.01) and WM FA (p=0.04). The crossing point of regression lines in POMS and AOMS was at 19 and 15 years of disease duration for GMV and WM FA, respectively. Median disease duration to reach EDSS=3 was 29 years for POMS and 19 years for AOMS patients (p<0.001), to reach brain GM volume z-score=-1.645 was 24 years for POMS and 19 years for AOMS (p=0.04), and to reach brain WM FA z-score=-1.645 was 19 years for POMS and 17 years for AOMS (p=0.31).

Conclusions

In POMS patients, disruption of WM integrity precedes GM damage and is initially less severe than in AOMS. The rate of WM damage accumulation is higher in POMS compared to AOMS, resulting in more severe WM damage with longer disease duration. Except for WM damage, POMS patients reach clinical and MRI milestones at younger age than AOMS, but take longer time.

Funding. Partially supported by grants from Italian Ministry of Health (GR-2009-1529671) and Fondazione Italiana Sclerosi Multipla (FISM2016/R/23).

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