Scans that chart the distribution of fluid within the brain during infancy could predict the later development of autism spectrum disorder (ASD) and the risk for developing ASD-related sleep problems, suggests a study funded by the National Institutes of Health.
The researchers used magnetic resonance imaging to detect cerebrospinal fluid, which bathes the brain and spinal cord. At 24 months of age, children with enlarged perivascular spaces—fluid-filled spaces surrounding small blood vessels in the brain—had a higher risk for an ASD diagnosis and higher chances for ASD-related sleep problems between ages 7 and 12.
The study was conducted by Dea Garic, Ph.D., and Mark Shen, Ph.D., of the University of North Carolina School of Medicine, and colleagues. It appears in JAMA Network Open. Funding was provided by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Background
Previous studies indicate that perivascular spaces are important for clearing waste products from the brain. In older people, malfunction of this clearance process is associated with certain neurological disorders and cognitive decline. Other studies in older adults have linked enlarged perivascular spaces with sleep problems.
A previous study suggested that children with enlarged perivascular spaces may be 5 times more likely to have developmental delays and 12 times more likely to have psychiatric problems. Other studies suggest that enlarged perivascular spaces are more common in children with ASD, but these studies included only a small number of children. Moreover, the studies detected enlarged perivascular spaces in children already diagnosed with ASD and could not determine whether the enlargement preceded the diagnosis.
For the current study, researchers sought to determine how early perivascular space enlargement begins in the brain and whether it is associated with a diagnosis of ASD and sleep problems. They analyzed data from an ongoing study 
of children at risk for ASD because they have an older sibling diagnosed with ASD.
They categorized the participants into three groups, based on their likelihood of developing ASD. The first—those with a sibling with ASD and who later developed ASD themselves—were designated high likelihood, positive. Those with a sibling with ASD but who did not develop ASD were high likelihood, negative. The control group—those whose siblings did not have ASD and who did not develop ASD—
were low likelihood, negative.
Results
A total of 311 participants were included in the analysis. Participants with enlarged perivascular spaces had more than double the chance of developing ASD, compared to other participants who also had an older sibling with ASD. Of the high likelihood, positive group, 21 (44.7%) had enlarged perivascular spaces at 24 months, compared to 48 participants (26.7%) in the high likelihood, negative group and 22 participants (26.2%) in the control group.
Enlarged perivascular spaces at 24 months were associated with a greater volume of extra axial cerebrospinal fluid (between the brain and inner lining of the skull) at 6 to 24 months and a greater likelihood of sleep problems from ages 7 to 12.
Significance
The researchers hypothesized that the presence of excess cerebrospinal fluid may indicate that the fluid is circulating more slowly than it should, potentially leading the perivascular space to widen. The findings may lead to earlier diagnosis of ASD in children, allowing clinicians to intervene and improving the chances for successful outcomes.
Reference
Garic, D, et al. Enlarged perivascular spaces in infancy and autism diagnosis, cerebrospinal fluid volume, and later sleep problems. JAMA Network Open. 2023.
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