Wide-spread brain alterations early after the onset of Crohn's disease in children in remission-a pilot study

Abstract

Background: The research on possible cerebral involvement in Crohn's disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI).

Objective: This cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset.

Methods: 14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss.

Results: While no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy.

Conclusion: Although still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.

Keywords: Crohn’s disease; MRI relaxometry; brain oedema; diffusion tensor imaging; neuroinflammation.

Figure 1

Main results of the comparison between patients with Crohn’s disease (CD) and healthy controls (HC) presented only for metrics detecting statistically significant results: mean diffusivity, fractional anisotropy, intracellular volume fraction and orientation dispersion index. Alpha of 0.05, within-modality false discovery rate corrected was implemented. Red-yellow scale marks CD > HC contrast, blue scale labels the reverse contrast; values correspond to the T statistic. Subcortical structures shown in 4 slices z = 20, 2, −16, −34 (MNI coordinate system). Laterality convention where the right side of the figure corresponds to the right side of the brain is used. No statistically significant findings in subcortical structures for mean diffusivity and intracellular volume fraction, and in cortical structures for orientation dispersion index. See Table 2 for full anatomical and statistical information on significant regions. L – left; R – right. For the full list of abbreviations and information on the parcellation, see Glasser et al. (2016).

Figure 2

Results of the analysis of correlation of disease duration before the treatment initiation in patients with Crohn’s disease and MRI parameters, presented only for metrics detecting statistically significant results: mean diffusivity and intracellular volume fraction. (A) Anatomical distribution of the findings. Red-yellow scale marks positive correlation, blue scale the reverse contrast; values correspond to the R statistic. Alpha of 0.05, false discovery rate corrected was implemented. Subcortical structures shown in 4 slices z = 20, 2, −16, −34 (MNI coordinate system). Laterality convention where the right side of the figure corresponds to the right side of the brain is used. No statistically significant findings in subcortical structures for mean diffusivity. (B) Scatterplots of relevant MRI metrics (x axis – months of disease duration, y axis – respective MRI metric) over relevant regions of interest with linear trendlines overlaid. See Table 3 for full anatomical and statistical information on significant regions. L – left; R – right.