Cerebrospinal fluid (CSF) circulates through small channels that surround blood vessels in the brain, which are known as perivascular spaces and are involved in removing waste and toxins from the brain to prevent neuroinflammation. A disruption in this key process can lead to neurological dysfunction, cognitive decline, or developmental delays.
New research by scientists in the Department of Psychiatry at the UNC School of Medicine has found that babies who have abnormally enlarged perivascular spaces are 2.2 times more likely to develop autism compared to babies with the same genetic risk. . Their research has also revealed that enlarged perivascular spaces in childhood are associated with sleep problems seven to 10 years after diagnosis.
The results have been published in JAMA Network Open and suggest that “perivascular spaces could serve as an early marker for autism,” said Dea Garic, assistant professor of psychiatry at UCN, member of the Carolina Institute for Developmental Disabilities. (CIDD) and main author of the work.
Researchers studied babies who were more likely to develop autism because they had an older sibling with the disorder. They followed these babies from six to 24 months of age, before they were diagnosed with autism, and found that 30% of the babies who later developed autism had enlarged perivascular spaces at 12 months. By 24 months of age, almost half of the babies diagnosed with autism had enlarged perivascular spaces.
Anomalies that affect brain development in early childhood
Every six hours, the brain expels a wave of CSF that flows through the perivascular spaces to remove potentially harmful neuroinflammatory proteins, such as Alzheimer’s-associated amyloid beta. The CSF clearance process is especially efficient while we sleep, since most CSF circulation and clearance occurs during sleep. Disrupted sleep can reduce CSF clearance from perivascular spaces, causing them to dilate or enlarge, but this has only been previously studied in animal studies or in studies in adult humans. This is the first study of its kind in children.
Garic hypothesized that CSF abnormalities in childhood would be related to later sleep problems, based on previous research by Shenés. The current sleep analysis revealed that children who had expanded perivascular spaces at age two had higher rates of sleep disorders at school age.
“CSF abnormalities in the first year of life could have side effects such as later diagnosis of autism, sleep problems, neuroinflammation, and possibly other developmental disabilities.”
“Because autism is so closely linked to sleep problems, we were in this unique position to examine the dynamics of CSF and sleep,” Garic said. “It was really surprising to observe such a strong association separated by such a long period of time during childhood. “But it really shows how perivascular spaces not only have an effect early in life, but can also have long-term effects.”
Garic and Mark Shen, the study’s other author, analyzed 870 MRI scans to measure excessive CSF volume and enlarged perivascular spaces. MRI scans were obtained from babies during natural sleep at six, 12, and 24 months of age to observe changes over time.
The baby’s brain undergoes rapid development during this period. Previously, measuring perivascular spaces was only thought to be clinically relevant to aging disorders in older adults, such as dementia, but the new findings suggest that younger people should be monitored for these types of brain abnormalities.
“Our findings were surprising, given that neuroradiologists typically view enlarged perivascular spaces as a sign of neurodegeneration in adults, but this study reported it in young children,” Garic said. “This is an important aspect of brain development in the first years of life that must be monitored.”
Garic and Shen hypothesize that excess CSF volume is stagnant and not circulating through the brain as efficiently as it should, so their next research goal is to use MRI to measure CSF in the brain of a sleeping baby, but this time focusing on the physiology and rate of CSF flow through the brain.
“Taken together, our research has shown that CSF abnormalities in the first year of life could have secondary effects on a variety of outcomes, including later diagnosis of autism, sleep problems, neuroinflammation, and possibly other developmental disabilities,” concludes Shen.
