Modeling disease trajectory in Duchenne muscular dystrophy
| Autor: | William T. Triplett, Sean C. Forbes, Barry S. Russman, Claudia R. Senesac, G. Tennekoon, Harneet Arora, Rebecca J. Willcocks, Erika Finanger, Michael J. Daniels, Dah Jyuu Wang, Richard S. Finkel, William D. Rooney, Yosef A. Berlow, Elliott O'Brien, Donovan J. Lott, Saptarshi Chakraborty, Brendan Moloney, Alison M. Barnard, Krista Vandenborne, H. Lee Sweeney, Ishu Arpan, Glenn A. Walter |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Magnetic Resonance Spectroscopy Adolescent Duchenne muscular dystrophy Population Corticosteroid treatment Walking Article 03 medical and health sciences 0302 clinical medicine Adrenal Cortex Hormones Internal medicine medicine Humans Muscular dystrophy Child Muscle Skeletal education Leg education.field_of_study medicine.diagnostic_test Disease trajectory business.industry Disease progression Therapeutic effect Magnetic resonance imaging medicine.disease Magnetic Resonance Imaging Muscular Dystrophy Duchenne 030104 developmental biology Child Preschool Disease Progression Cardiology Female Neurology (clinical) business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Neurology |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000009244 |
| Popis: | ObjectiveTo quantify disease progression in individuals with Duchenne muscular dystrophy (DMD) using magnetic resonance biomarkers of leg muscles.MethodsMRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired from 104 participants with DMD and 51 healthy controls using a prospective observational study design with patients with DMD followed up yearly for up to 6 years. Fat fractions (FFs) in vastus lateralis and soleus muscles were determined with 1H MRS. MRI quantitative T2 (qT2) values were measured for 3 muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach.ResultsMRS FF and MRI qT2 increased with DMD disease duration, with the progression time constants differing markedly between individuals and across muscles. The average age at half-maximal muscle involvement (μ) occurred 4.8 years earlier in vastus lateralis than soleus, and these measures were strongly associated with loss-of-ambulation age. Corticosteroid treatment was found to delay μ by 2.5 years on average across muscles, although there were marked differences between muscles with more slowly progressing muscles showing larger delay.ConclusionsMRS FF and MRI qT2 provide sensitive noninvasive measures of DMD progression. Modeling changes in these biomarkers across multiple muscles can be used to detect and monitor the therapeutic effects of corticosteroids on disease progression and to provide prognostic information on functional outcomes. This modeling approach provides a method to transform these MRI biomarkers into well-understood metrics, allowing concise summaries of DMD disease progression at individual and population levels.ClinicalTrials.gov identifier:NCT01484678. |
| Databáze: | OpenAIRE |
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