June 2026 Research Update

This month added a clearer picture of how metachromatic leukodystrophy (MLD) can look on brain MRI when compared against large, age-based brain growth charts: many brain regions may look relatively preserved in size, even while other signs of disease are present. In the same dataset, enlarged fluid spaces in the brain (ventriculomegaly) showed up across all the leukodystrophies studied, including MLD. Taken together, these studies suggest that tracking MLD on MRI may not always be about simple shrinkage of brain regions, and that more tailored imaging markers may be needed. [1]

To do this, researchers used automated computer methods to measure global and regional brain volumes from clinical MRIs, then converted these into centile scores that show where a child falls compared with typical development. When comparing different leukodystrophies side by side, the study reported that AxD and MLD tended to show relative volume preservation or increase in many regions, while several other leukodystrophies showed widespread volume loss. This matters because it points to disease-specific MRI patterns rather than one shared pattern across all leukodystrophies. [1]

The study also tested whether these centile-based MRI measures lined up with how severely children were affected. It reported that links between motor function severity scores and regional brain volumes were present within diagnoses, but the strength and locations of these links differed by disease, and for AxD the correlations were minimal after statistical correction (MLD-specific correlation details were not spelled out in the summary). The researchers also noted early, preliminary hints from limited follow-up scans that these measures could be useful for tracking change over time, but they emphasized that more longitudinal data are needed. [1]

For families affected by MLD, this study mainly adds research-level context for how MRI measurements might be interpreted in the future. It suggests that in MLD, brain volume on MRI may not simply and steadily decrease in the way some people might expect, and that some commonly used volume measures may need to be combined with other markers to reflect disease burden. This does not provide a ready-to-use test for individuals yet, but it supports ongoing work toward imaging measurements that could eventually help describe severity and monitor progression in a more standardized way. [1]

What remains uncertain is how well these centile scores track meaningful changes for a given child with MLD over time, because the report described only preliminary longitudinal signals and noted limited longitudinal data. Another open question is how results might vary across hospitals and scanners, since the study included multiple centers and noted scanner and site differences as a limitation. Even with these uncertainties, the work helps clarify that MLD should be evaluated with MLD-specific expectations on MRI rather than assuming all leukodystrophies follow the same imaging pattern. [1]