Constructing an Axonal‐Specific Myelin Developmental Graph and its Application to Childhood Absence Epilepsy

Abstract

The process of myelination starts in utero around 20 weeks of gestation and continues through adulthood. We first set out to characterize the maturation of the tract-specific myelin content in healthy subjects from childhood (7-12 years) into adulthood (18-32 years). Second, we apply the resulting development graph to children with childhood absence epilepsy (CAE), a pediatric epilepsy that was previously characterized by changes in myelin content. METHODS: In a prospective cross-sectional study, 15 healthy children (7-12 years), 14 healthy adult participants (18-32 years) and 17 children with a clinical diagnosis of CAE (6-12 years) were included. For each participant, diffusion weighted images were acquired to reconstruct bundles of white matter tracts and multi-echo multi-slice GRASE images were acquired for myelinwater estimation. Subsequently, a tract-specific myelin development graph was constructed using the percentual difference in myelin-water content from childhood (12 year) to adulthood (25 year). RESULTS: The graph revealed myelination patterns, where tracts in the central regions myelinate prior to peripheral tracts and intra-hemispheric tracts as well as tracts in the left hemisphere myelinate prior to inter-hemispheric tracts and tracts in the right hemisphere, respectively. No significant differences were found in myelin-water content between children with CAE and healthy children for neither the early developing tracts, nor the tracts that develop in a later stage. However, the difference between the myelin-water of late and early developing tracts is significantly smaller in the children with CAE. CONCLUSION: These results indicate that CAE is associated with widespread neurodevelopmental myelin differences.

Alterations in white matter integrity and asymmetry in patients with benign childhood epilepsy with centrotemporal spikes and childhood absence epilepsy: An automated fiber quantification tractography study

“…Thus, we speculate that the presence of linguistic impairment in patients with CAE is probably at least partially associated with the abnormal lateralization of the IFOF and AF. Moreover, a study investigating the development of tract-specific myelin content in patients with CAE showed that the fiber tracts in the left hemisphere were myelinated in an earlier stage, suggesting myelination of fiber tracts also demonstrate left lateralization [59]. The LI calculated in our study was based on FA values, to some extent, the altered lateralization of fiber tracts in CAE may indicate the delayed neurodevelopment in myelination.…”

Update on myelin imaging in neurological syndromes

“…Pediatric studies show a rapid increase in MWF during the first 2–3 years of life, especially in brain regions related to social and emotional development, with myelination continuing at a slower rate from the age of 7 onwards as MWF values approach those of adult brain [12 ▪▪ ,13,14].…”