Evidence for compromised function of the glymphatic system in pediatric acquired demyelinating disorders

Impairments in the glymphatic system (GS) have been found in adults with acquired demyelinating syndromes (ADS), suggesting disruptions to the brain's waste clearance system may contribute to disease symptoms. However, this system has not been well characterized in pediatric ADS (PADS) populations. In the present study, we assessed the GS function in 15 children with PADS using the recently developed diffusion tensor along the perivascular space (DTI-ALPS) method. DTI-ALPS was also assessed in a group of healthy comparison (HC) subjects and in a subset of patients six months after relapse. Significant reductions in DTI-ALPS index, reflective of disrupted GS function, were found in both left and right in the PADS group relative to HC group (ps < 0.01). ALPS indices were not associated with neurocognitive screening results (ps > 0.12). Additionally, in seven of the eight participants with PADS for whom follow-up data were available, the ALPS index increased at follow-up- though this was not significant at a group level (ps = 0.06-0.13). Lastly, we found no significant relationships between ALPS index and lesion or white matter metrics, suggesting DTI-ALPS may be independent. Our results show pediatric patients with demyelinating disorders have a lower ALPS index, as has been demonstrated in adults. These findings suggest ALPS could be an additional index of disease expression. Larger studies are needed to replicate these findings.