Neurodegeneration trajectory in pediatric and adult/lateDM1: A follow-up MRI study across a decade

Garazi Labayru, Antonio Jimenez-Marin, Esther Fernandez, Jorge Villanua, Miren Zulaica, Jesus M. Cortes, Ibai Diıez, Jorge Sepulcre, Adolfo Lopez de Munain, Andone Sistiaga. Neurodegeneration trajectory in pediatric and adult/lateDM1: A follow-up MRI study across a decade. Annals of Clinical and Translational Neurology 7:1802-1815, 2020 [pdf]

Objective: To characterize the progression of brain structural abnormalities in adults with pediatric and adult/late onset DM1, as well as to examine the potential predictive markers of such progression.

Methods: 21 DM1 patients (pediatric onset: N = 9; adult/late onset: N = 12) and 18 healthy controls (HC) were assessed longitudinally over 9.17 years through brain MRI. Additionally, patients underwent neuropsychological, genetic, and muscular impairment assessment. Inter-group comparisons of total and voxel-level regional brain volume were conducted through Voxel-Based Morphometry (VBM); cross-sectionally and longitudinally, analyzing the associations between brain changes and demographic, clinical, and cognitive outcomes.

Results: The percentage of GM loss did not significantly differ in any of the groups compared with HC and when assessed independently, adult/late DM1 patients and their HC group suffered a significant loss in WM volume. Regional VBM analyses revealed subcortical GM damage in both DM1 groups, evolving to frontal regions in the pediatric-onset patients. Muscular impairment and the outcomes of certain neuropsychological tests were significantly associated with follow-up GM damage, while visuoconstruction, attention, and executive function tests showed sensitivity to WM degeneration over time.

Interpretation: Distinct patterns of brain atrophy and its progression over time in pediatric and adult/late onset DM1 patients are suggested. Results indicate a possible neurodevelopmental origin of the brain abnormalities in DM1, along with the possible existence of an additional neurodegenerative process. Fronto-subcortical networks appear to be involved in the disease progression at young adulthood in pediatric-onset DM1 patients. The involvement of a multimodal integration network in DM1 is discussed.

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