To characterize neuroimaging findings in patients with Canavan Disease in relation to the known process of myelination during early childhood.

The normal myelination process is incomplete at birth and proceeds during early development from caudal to rostral and posterior to anterior regions of the brain. Canavan Disease is an autosomal recessive leukodystrophy characterized by spongiform degeneration and myelin loss of the CNS.

All patients with a diagnosis of Canavan Disease and with prior MRI imaging available evaluated in a leukodystrophy clinic between 2019-2022 outside of an interventional trial were included. Each MRI was evaluated for the presence of T2 signal abnormalities in structures previously implicated in Canavan Disease, as well as the presence of edema and atrophy.

Fourteen MRIs obtained from 9 individuals were included for analysis. Age at time of MRI ranged from 8 weeks to 5 years. Imaging obtained during the first six months of life (n=6) revealed T2 signal abnormalities most prominent in the dorsal brainstem and cerebellum with some hyperintensity in the parieto-occipital white matter and relative frontal sparing. Edema, if present, was mild and primarily seen in the brainstem. Atrophy was not a major feature. Between 6 months and 2 years (n=2), supratentorial T2 signal abnormalities were prominent, with a continued anterior-posterior gradient. Edema was more apparent, involving both the brainstem and posterior supratentorial regions, although atrophy remained uncommon. At age 2 years and above (n=6), edema was less prominent and, when present, mostly occurring in the frontal regions. Significant atrophy was present in the brainstem and parieto-occipital regions with relative frontal sparing.

MRI changes in this cohort varied by age, showing evidence of initial T2 signal abnormality followed by edema and ultimately atrophy, with a temporospatial distribution following the typical pattern of developing myelination. This suggests that developing myelination drives the the injury seen.