White matter microstructural abnormalities in children with severe congenital hypothyroidism.

Change log
Cooper, Hannah E 
Kaden, Enrico 
Halliday, Lorna F 
Bamiou, Doris-Eva 
Mankad, Kshitij 

This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.

Communication, Diffusion tensor imaging, Endocrine, Hearing, MRI, Adolescent, Child, Cognitive Dysfunction, Communication Disorders, Congenital Hypothyroidism, Diffusion Tensor Imaging, Female, Hearing Loss, Humans, Language Disorders, Male, Severity of Illness Index, White Matter
Journal Title
Neuroimage Clin
Conference Name
Journal ISSN
Volume Title
Elsevier BV
This work was supported by a NIHR/CSO Healthcare Science Doctoral Research Fellowship, Hannah Cooper, NIHR-HCS-D12-03-05. We also acknowledge funding from the NIHR Biomedical Research Centre at Great Ormond Street Hospital and the Great Ormond Street Institute of Child Health, University College London, as well as at University College London Hospitals. Enrico Kaden was supported by grants UK EPSRCEP/M020533/1, EP/N018702/1 and EU H2020 634541-2.