Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.

Leddy, S., Serra, L., Esposito, D., Vizzotto, C., Giulietti, G., Silvestri, G., Petrucci, A., Meola, G., Lopiano, L., Cercignani, M., Bozzali, M., Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis, <<NEUROIMAGE. CLINICAL>>, 2021; 29 (29): 102562-N/A. [doi:10.1016/j.nicl.2021.102562] [http://hdl.handle.net/10807/182931]

Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis

Silvestri, Gabriella;
2021

Abstract

Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.
2021
Inglese
Leddy, S., Serra, L., Esposito, D., Vizzotto, C., Giulietti, G., Silvestri, G., Petrucci, A., Meola, G., Lopiano, L., Cercignani, M., Bozzali, M., Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis, <<NEUROIMAGE. CLINICAL>>, 2021; 29 (29): 102562-N/A. [doi:10.1016/j.nicl.2021.102562] [http://hdl.handle.net/10807/182931]
File in questo prodotto:
File Dimensione Formato  
Neuroimage Clinical 2021 WM in DM1.pdf

accesso aperto

Tipologia file ?: Postprint (versione finale dell’autore successiva alla peer-review)
Licenza: Creative commons
Dimensione 2.47 MB
Formato Adobe PDF
2.47 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/182931
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 9
social impact