Diffusion Tensor Imaging in Pediatric NMDAR Encephalitis with Grossly Normal MRI Reveals Widespread Changes of Subcortical Microstructure Compared to Healthy Controls
Alexander Sandweiss1, Jonathan Yarimi1, Jesse Levine1, Varun Kannan1, Kristen Fisher1, Nilesh Desai1, Stephen Kralik1
1Baylor College of Medicine
Objective:
To compare the microstructural subcortical white matter changes in children with NMDAR encephalitis and grossly normal MRIs to that of age- and sex- matched healthy controls.
Background:
Pediatric NMDAR encephalitis is an antibody-mediated autoimmune neuropsychiatric condition characterized by focal weakness, language deficits, seizures, movement disorder, psychosis, and autonomic dysfunction. Children often have normal MR imaging of the brain at presentation, obscuring—and potentially delaying—any potential neurologic workup. Deficits in NMDAR encephalitis may be associated with previously unidentified microstructural changes.
Design/Methods:
This is a case control study comparing diffusion tensor imaging (DTI) in children with NMDAR encephalitis (n=10) to those of age- and sex- matched healthy controls (n=30). Most control patients were evaluated with MRI for headache and all images obtained in both groups were performed on the same equipment. In brief, the FMRIB Software Library (Oxford) suite was used to compare tract-based spatial statistics (TBSS) of DTI data following a standardized sequence of denoising, removing artifacts, aligning images, and performing voxel-based statistics.
Results:
Children with NMDAR encephalitis and grossly normal MRIs (n=10) had significantly reduced fractional anisotropy (FA) in the internal capsule, corpus callosum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and arcuate fasciculus, all affecting the right-side greater than left (p<0.05), compared to healthy controls (n=30). On average, the NMDAR encephalitis group had significantly higher mean diffusivity (MD) and radial diffusivity (RD) in the same subcortical white matter regions, overall indicating reduced axonal caliber, myelination, and perhaps long-tract atrophy compared to controls.
Conclusions:
Pediatric NMDAR encephalitis with grossly normal MRI may be identified by microstructural changes on DTI. These changes correlate to pediatric NMDAR encephalitis symptoms and may represent the underlying pathogenesis of disease. Future studies are needed to evaluate the dynamic nature of subcortical white matter microstructural changes over the course of disease.