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Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I
Victor Kovac1, Elsa G Shapiro1, Kyle D Rudser2
1Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
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.
Insights
Brain structure differences were found in individuals with mucopolysaccharidosis type I (MPS I) compared to healthy controls. These brain macrostructure alterations, including cortical thickness and white matter volume, were evident even in young children with MPS I.
Area of Science:
- Neuroimaging
- Genetics
- Pediatrics
Background:
- Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder affecting multiple organs.
- Brain macrostructure alterations are suspected in MPS I, but comprehensive quantitative data is limited.
- Understanding these changes is crucial for managing neurocognitive outcomes.
Purpose of the Study:
- To investigate differences in brain macrostructure between individuals with MPS I and healthy controls.
- To analyze how disease phenotype, age, and cognition influence brain structure in MPS I.
- To differentiate between attenuated (MPS IA) and severe (MPS IH) forms of MPS I using neuroimaging.
Main Methods:
- A multicenter quantitative magnetic resonance imaging (qMRI) study was performed.
- Brain MRIs of 23 MPS I patients (4-25 years) and 98 healthy controls were analyzed.
- Analyses accounted for disease phenotype, age, and cognitive status.
Main Results:
- Significant differences in gray matter, white matter, corpus callosum, and ventricular volumes were observed between MPS I and healthy controls.
- Thicker cortex and reduced white matter/corpus callosum volumes were present in young MPS I participants (4-5 years).
- Age-related brain changes were more pronounced in severe MPS I (MPS IH), particularly in cortical gray matter; IQ correlated with ventricular volume and cortical thickness.
Conclusions:
- Quantitative MRI measures effectively distinguish MPS I from healthy controls and different MPS I subtypes.
- Age-related neurodevelopmental trajectories in MPS I differ from healthy individuals.
- Further research is needed to understand the impact of disease and treatment on brain structure and neurocognition in MPS I.
