Victor Kovac1, Elsa G Shapiro2, Kyle D Rudser3, Bryon A Mueller4, Julie B Eisengart5, Kathleen A Delaney6, Alia Ahmed7, Kelly E King8, Brianna D Yund9, Morton J Cowan10, Julian Raiman11, Eva G Mamak12, Paul R Harmatz13, Suma P Shankar14, Nadia Ali15, Stephanie R Cagle16, Jeffrey R Wozniak17, Kelvin O Lim18, Paul J Orchard19, Chester B Whitley20, Igor Nestrasil21. 1. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: vjwkovac@gmail.com. 2. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: shapi004@umn.edu. 3. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: rudser@umn.edu. 4. Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: muell093@umn.edu. 5. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: eisen139@umn.edu. 6. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: delan011@umn.edu. 7. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: ahmed306@umn.edu. 8. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: kingx780@umn.edu. 9. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: bdy@umn.edu. 10. UCSF Benioff Children's Hospital, University of California, San Francisco, CA, USA. Electronic address: mort.cowan@ucsf.edu. 11. Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: julian.raiman@nhs.net. 12. Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: eva.mamak@sickkids.ca. 13. UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA. Electronic address: pharmatz@mail.cho.org. 14. Department of Ophthalmology and Human Genetics, Emory University, Atlanta, GA, USA. Electronic address: spshankar@ucdavis.edu. 15. Department of Human Genetics, Emory University, Atlanta, GA, USA. Electronic address: nadia.ali@emory.edu. 16. Department of Human Genetics, Emory University, Atlanta, GA, USA. 17. Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: jwozniak@umn.edu. 18. Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: kolim@umn.edu. 19. Division of Pediatric Blood & Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: orcha001@umn.edu. 20. Gene Therapy Center, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: whitley@umn.edu. 21. Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Center for Magnetic Resonance Research (CMRR), Department of Radiology, Minneapolis, MN, USA. Electronic address: nestr007@umn.edu.
Abstract
OBJECTIVE: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. METHODS: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. RESULTS: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. CONCLUSIONS: Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.
OBJECTIVE: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. METHODS: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. RESULTS: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. CONCLUSIONS: Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.
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