Tracking the brain in myotonic dystrophies: A 5-year longitudinal follow-up study

PLoS One. 2019 Mar 7;14(3):e0213381. doi: 10.1371/journal.pone.0213381. eCollection 2019.

Abstract

Objectives: The aim of this study was to examine the natural history of brain involvement in adult-onset myotonic dystrophies type 1 and 2 (DM1, DM2).

Methods: We conducted a longitudinal observational study to examine functional and structural cerebral changes in myotonic dystrophies. We enrolled 16 adult-onset DM1 patients, 16 DM2 patients, and 17 controls. At baseline and after 5.5 ± 0.4 years participants underwent neurological, neuropsychological, and 3T-brain MRI examinations using identical study protocols that included voxel-based morphometry and diffusion tensor imaging. Data were analyzed by (i) group comparisons between patients and controls at baseline and follow-up, and (ii) group comparisons using difference maps (baseline-follow-up in each participant) to focus on disease-related effects over time.

Results: We found minor neuropsychological deficits with mild progression in DM1 more than DM2. Daytime sleepiness was restricted to DM1, whereas fatigue was present in both disease entities and stable over time. Comparing results of cross-sectional neuroimaging analyses at baseline and follow-up revealed an unchanged pattern of pronounced white matter alterations in DM1. There was mild additional gray matter reduction in DM1 at follow-up. In DM2, white matter reduction was of lesser extent, but there were some additional alterations at follow-up. Gray matter seemed unaffected in DM2. Intriguingly, longitudinal analyses using difference maps and comparing them between patients and controls did not reveal any significant differences of cerebral changes over time between patients and controls.

Conclusion: The lack of significant disease-related progression of gray and white matter involvement over a period of five years in our cohort of DM1 and DM2 patients suggests either a rather slowly progressive process or even a stable course of cerebral changes in middle-aged adult-onset patients. Being the first longitudinal neuroimaging trial in DM1 and DM2, this study provides useful additional information regarding the natural history of brain involvement.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Cross-Sectional Studies
  • Diffusion Tensor Imaging / methods
  • Female
  • Follow-Up Studies
  • Gray Matter / pathology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Myotonic Dystrophy / pathology*
  • Neuropsychological Tests
  • White Matter / pathology*

Grants and funding

The Marigold Foundation (registered Canadian Charity Organisation) and the Deutsche Gesellschaft für Muskelkranke e.V. (Me4/1) partly financed study examinations, investigators salaries, and data analysis. The Marigold Foundation and the Deutsche Gesellschaft für Muskelkranke e.V. had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.G. received funding from the Deutsche Gesellschaft für Muskelkranke e.V. (Me4/1). M.M. received funding from Maria von Linden-Support Programme of the University of Bonn, Germany. J.-C.S-B received a grant as part of the Gerok Programme of the BONFOR commission, University of Bonn, and grants from the Deutsche Forschungsgemeinschaft (SFB TR3). R.C.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) with a Heisenberg grant (BE 2346/4-2). M.T. has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), and the European Union (EU). T.K. has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Robert Bosch Foundation and the European Union (EU). C.K. has received research support from the Bundesministerium für Bildung und Forschung (BMBF: 01GM0862), the Deutsche Gesellschaft für Muskelkranke e.V. (Me4/1) and The Marigold Foundation, Canada.