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

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.

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

“…However, these results contrast with other attempts at longitudinal MRI assessment that found no loss over a period of 5 years. 7 The longer timespan employed in the present work compared with the latter, could explain the potential progression of atrophy found in this study.…”

Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats

“…Future studies would also benefit from a longitudinal design. Of note, recent data from Gliem and colleagues [65] suggest the rate of structural brain change over time may be slow, and hence could be challenging to measure within the timescale of a typical clinical trial. Further, respiratory function was not specifically assessed as part of the present study.…”

Characterization of Iron Accumulation in Deep Gray Matter in Myotonic Dystrophy Type 1 and 2 Using Quantitative Susceptibility Mapping and R2* Relaxometry: A Magnetic Resonance Imaging Study at 3 Tesla

“…A 5 years follow-up MRI study in DM1 and DM2 revealed mainly stable findings, but there was a mild progression of GM reduction in DM1 (17).…”

“…Effects of altered cerebral levels of myelin, calcium could theoretically play a role in susceptibility or R2 * of brain tissue. In DM1 and DM2 myelin changes due to slowly evolving demyelinating processes mainly related to formation of white matter lesions have been observed (13,17). Furthermore, dysregulation of calcium metabolism (30,31), e.g., due to calcium channel dysfunction, as discussed in the pathogenesis of restless legs symptoms (RLS) in DM2 (32) could potentially influence QSM and R2 * measures.…”