A Longitudinal Study of Disability, Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity

Gro O Nygaard; Elisabeth G Celius; Sigrid A de Rodez Benavent; Piotr Sowa; Marte W Gustavsen; Anders M Fjell; Nils I Landrø; Kristine B Walhovd; Hanne F Harbo

doi:10.1371/journal.pone.0135974

A Longitudinal Study of Disability, Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity

PLoS One. 2015 Aug 17;10(8):e0135974. doi: 10.1371/journal.pone.0135974. eCollection 2015.

Authors

Gro O Nygaard¹, Elisabeth G Celius¹, Sigrid A de Rodez Benavent², Piotr Sowa³, Marte W Gustavsen¹, Anders M Fjell⁴, Nils I Landrø⁴, Kristine B Walhovd⁴, Hanne F Harbo¹

Affiliations

¹ Department of Neurology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
² Department of Ophthalmology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Radiology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Psychology, University of Oslo, Oslo, Norway.

Abstract

New treatment options may make "no evidence of disease activity" (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to "evidence of disease activity" (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8-2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0-1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Atrophy / pathology*
Brain / pathology
Cognition / physiology*
Disability Evaluation
Disabled Persons
Disease Progression
Female
Gray Matter / pathology*
Humans
Longitudinal Studies
Magnetic Resonance Imaging / methods
Male
Multiple Sclerosis, Relapsing-Remitting / pathology*
Nerve Fibers, Myelinated / pathology
Recurrence

Grants and funding

This work was funded by the South-Eastern Health Authorities of Norway (grant number 2011059, entitled ‘Genetic risk factors and MRI and clinical outcome in MS’) and a research grant from the Odd Fellows Foundation for Multiple Sclerosis Research. This funding was external to our organization. The first author received a PhD scholarship from the former, and the research assistants who performed neuropsychological testing of the patients were supported by the latter grant, both of which were administered by Oslo University Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.