New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study

PLoS One. 2017 Nov 17;12(11):e0184650. doi: 10.1371/journal.pone.0184650. eCollection 2017.

Abstract

Objective: In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions.

Methods: EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected).

Results: At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0-3] at Year 1 to 2.5 [range: 0-6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression.

Conclusion: The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.

MeSH terms

  • Adolescent
  • Adult
  • Cognition Disorders / complications*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / complications
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Multiple Sclerosis, Relapsing-Remitting / psychology
  • Neuropsychological Tests
  • Young Adult

Grants and funding

Dr. Pelletier serves on scientific advisory boards for Biogen Idec, Genzyme, Novartis and Teva. This study was supported by grants from the Association pour la Recherche sur la Sclérose En Plaques (ARSEP) and CNRS, and was funded by an unconditional grant from Merck Serono France. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The data are ethically restricted because of medical confidentiality. Any request needs to be approved by our local Committee, named "Comité d'Ethique de la Timone." Requests for the data should be sent to the corresponding author. Dr Wybrecht, Dr Reuter, Dr Pariollaud, Dr Zaaraoui, Dr Le Troter, Dr Rico, Dr Maarouf, Dr Confort-Gouny, Dr Soulier, Dr Ranjeva, Dr Audoin, Dr Guye report no disclosures.