summary: Researchers found that infants with abnormally enlarged perivascular spaces in the brain were 2.2 times more likely to develop autism.
Perivascular space enlargement was observed in infants as young as 12 months, and nearly half of infants diagnosed with autism experienced perivascular space enlargement by 24 months.
This study highlights the importance of cerebrospinal fluid (CSF) in maintaining brain health, and disruptions in CSF circulation can contribute to neurological dysfunction. This study provides new insights into the relationship between early markers of autism and children’s CSF dynamics, brain abnormalities, and sleep disturbances.
- Enlarged perivascular spaces in infants may serve as an early marker of autism, increasing risk by 2.2 times.
- Cerebrospinal fluid (CSF) plays an important role in maintaining brain health and removing neuroinflammatory proteins from the brain.
- This study suggests that CSF abnormalities during infancy may have long-term effects such as sleep disturbances and neuroinflammation.
Throughout the day and night, cerebrospinal fluid (CSF) pulsates through tiny fluid-filled channels surrounding the brain’s blood vessels, called the perivascular space, to flush out neuroinflammation and other neurological waste. Disruption of this critical process can result in neurological dysfunction, cognitive decline, or developmental delays.
Researchers Dia Garrick, Ph.D., and Mark Shen, Ph.D., from the UNC School of Medicine Department of Psychiatry, found that infants with abnormally enlarged perivascular spaces were 2.2 times more likely to develop autism than infants with the disorder. I discovered it for the first time. Same genetic risk. Their study also showed that enlargement of the perivascular space during infancy was associated with sleep disturbances 7 to 10 years after diagnosis.
“These results suggest that the perivascular space may serve as an early marker of autism,” said Garrick, a member of the Carolina Institute for Developmental Disabilities (CIDD) and assistant professor of psychiatry. he said.
Researchers studied young children who were more likely to develop autism because they had an older sibling with autism. The researchers followed these infants from 6 to 24 months of age, before they were diagnosed with autism.
Their research is JAMA network openfound that 30 percent of infants who later developed autism had enlarged perivascular spaces by 12 months of age. By 24 months of age, nearly half of infants diagnosed with autism had enlarged perivascular spaces.
The importance of cerebrospinal fluid and sleep
Over the past decade, there has been a resurgence of research into the important function of CSF in regulating brain health and development. Shen’s lab was the first to report that excess amounts of CSF are evident at 6 months of age in infants who later develop autism.
The current study showed that excess CSF volume at 6 months was associated with enlarged perivascular spaces at 24 months.
Every six hours, the brain drains a wave of CSF that flows through the perivascular space, preventing potentially harmful neuroinflammatory proteins such as amyloid beta from accumulating in the brain. The CSF cleaning process is particularly efficient during sleep because the majority of CSF circulation and clearance occurs during sleep.
However, when sleep is disrupted, CSF clearance from the perivascular space may be reduced, leading to dilatation or enlargement, which has so far only been studied in animal studies or human studies in adults. I did. This is the first study of its kind to involve children.
Shen, senior author of JAMA network open In the paper, Garlick hypothesized that CSF abnormalities in infancy might be associated with later sleep problems, based on Shen’s previous research. The current sleep analysis revealed that children with enlarged perivascular spaces at 2 years of age had a higher incidence of sleep disorders during school age.
“We were in a unique position to investigate CSF dynamics and sleep because autism is highly associated with sleep problems,” said Garic, lead author of the paper. “It was really shocking to see such a strong connection over such a long period of time throughout childhood. But not only does the perivascular space have an impact early in life, it also has long-term effects. It really shows you what you get.”
New clinical relevance in infancy
The study was conducted in conjunction with the Infant Brain Imaging Study (IBIS), a national network of researchers studying brain development, autism, and related developmental disorders. The network consists of five of his universities, with the University of North Carolina at Chapel Hill being its main hub.
For the study, Garic and Shen analyzed 870 MRIs from IBIS and measured excess CSF volume and enlarged perivascular spaces. MRI images were taken of naturally sleeping babies at 6, 12, and 24 months of age to observe changes over time.
Infants’ brains develop rapidly during this period. Previously, measurements of the perivascular space were only considered clinically relevant for age-related diseases in the elderly, such as dementia. These findings suggest that this type of brain abnormality may need to be considered and monitored in young adults.
“Our findings were surprising given that neuroradiologists typically consider perivascular space enlargement to be a sign of neurodegeneration in adults, but this study also reported it in young children. ,” Garic said. “This is an important aspect of brain development during the first few years of life and needs to be monitored.”
Future research and possibilities
Garic and Shen hypothesize that excess CSF volume may become stagnant or clogged and not circulate efficiently through the brain. For their next research effort, the researchers plan to use MRI again to measure CSF in the brains of sleeping infants, but this time they will look at the physiology and velocity of CSF flow throughout the brain. focused.
The research team is also working with other collaborators to quantify the size of perivascular spaces and the severity of behavioral outcomes. The research team also plans to expand their work to neurogenetic syndromes associated with autism, such as fragile X syndrome and Down syndrome.
“Taken together, our studies suggest that CSF abnormalities during the first year of life may have downstream effects on a variety of outcomes, including subsequent autism diagnosis, sleep disturbances, neuroinflammation, and possibly other developmental disorders.” “This has been shown to be the case,” Professor Shen said.
Funding: This research was supported by the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Mental Health (NIMH), the National Institute of Environmental Health Sciences (NIEHS), and the Simons Foundation. Ta.
Other researchers on this project include Joseph Pibun, MD; Dr. Heather C. Haslett. Dr. Martin Steiner; Dr. Seung Hyun Kim. Dr. Joshua Ratsohn. Lee Ann Weisenfeld, Massachusetts; University of North Carolina at Chapel Hill. Robert C. McKinstry, MD. Kelly N. Botteron, MD. Professor at Washington University in St. Louis. Rebecca Slomowitz, Massachusetts. from the University of Denver. Dr. Jason Wolfe. from the University of Minnesota. Lee C. McIntyre, Bachelor of Arts; Professor at McGill University. Dr. Juhi Pandey. from the University of Pennsylvania. and Dr. Tanya St. John. Dr. Annette M. Estes. Dr. Robert T. Schulz. Steven R. Dager, MD. from the University of Washington.
About this autism and sleep research news
author: Kendall Daniels
contact: Kendall Daniels – UNC
image: Image credited to Neuroscience News
Original research: Open access.
“Perivascular space enlargement in infancy and diagnosis of autism, cerebrospinal fluid volume, and subsequent sleep disturbances” Dea Garic et al. JAMA network open
Perivascular space enlargement in infancy and diagnosis of autism, cerebrospinal fluid volume, and subsequent sleep disturbances
The perivascular space (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, which regulates brain homeostasis and removes neural waste throughout life. Enlarged PVS is associated with neurological and sleep disorders in adults, and excessive CSF volume has been reported in infants who develop autism. PVS expansion has not been well studied in longitudinal studies during infancy and its association with autism outcome and his CSF volume.
Whether PVS expansions are more prevalent in infants who develop autism compared with controls and whether they are associated with extra-axial CSF volume (EA-CSF) trajectories and sleep disturbances from early childhood onwards. to find out what.
This prospective longitudinal cohort study used data from an infant brain imaging study. Magnetic resonance images were obtained at 6, 12, and 24 months of age (2007–2017), and sleep questionnaires were administered between 7 and 12 years of age (starting in 2018). Data was collected at his four locations in North Carolina, Missouri, Pennsylvania, and Washington. Data was analyzed from March 2021 to August 2022.
The PVS (i.e., the fluid-filled channels surrounding blood vessels in the brain) are enlarged (i.e., visible on magnetic resonance images).
Main results and measures
Results of interest were increased PVS and EA-CSF volumes from 6 to 24 months, autism diagnosis at 24 months, and sleep problems from 7 to 12 years of age.
Total of 311 infants (197 people) [63.3%] Forty-seven infants with a high probability of autism in their families (i.e., had an older sibling with autism) who were diagnosed with autism at 24 months of age; They included 180 infants who were likely not diagnosed, and 84 control infants who were unlikely to be diagnosed. With autism. School-age sleep strategies were available to 109 participants. Among infants who developed autism, 21 (44.7%) had expanded PVS at 24 months, compared to a group of infants who were likely not diagnosed with autism. There were 48 infants (26.7%) (P= .02), 22 infants (26.2%) in the control group (P= .03). Across all groups, expanded PVS at 24 months was associated with increased EA-CSF volume from 6 to 24 months of age (β = 4.64; 95% CI, 0.58-8.72; P= .002), and waking up at night becomes more frequent during school age (F= 7.76; η2= 0.08; P= .006).
Conclusion and relevance
These findings suggest that expanded PVS appeared between 12 and 24 months of age in infants who developed autism. These results add to growing evidence that glymphatic dysregulation may occur in infants who develop autism, in addition to excess CSF volume and sleep dysfunction. It corroborates this.