Enlarged Perivascular Spaces in Infancy and Autism Diagnosis, Cerebrospinal Fluid Volume, and Later Sleep Problems.

Researchers studied brain scans of 311 babies from 6-24 months and found that babies who later developed autism were more likely to have enlarged fluid-filled spaces around blood vessels in their brains. These enlarged spaces were linked to more brain fluid overall and more night wakings during school age. This suggests the brain's cleaning system may not work properly in children with autism.

This longitudinal cohort study examined enlarged perivascular spaces (PVS) in 311 infants, following them from 6-24 months with autism diagnoses at 24 months and sleep assessments at ages 7-12 years. Results showed that 44.7% of infants who developed autism had enlarged PVS at 24 months, compared to 26.7% in high-risk infants without autism and 26.2% in controls. Enlarged PVS at 24 months was associated with greater cerebrospinal fluid volume throughout infancy and more frequent night wakings at school-age. The findings suggest enlarged PVS emerged between 12-24 months in infants who later developed autism, supporting potential glymphatic system dysregulation in autism development alongside previously identified CSF abnormalities and sleep dysfunction.

Findings suggest potential for early neuroimaging markers of autism risk and highlight the importance of sleep monitoring in children with autism. Results support glymphatic system dysfunction as a mechanism underlying autism-related sleep problems and brain development differences.

Sample size for sleep measures was limited (109 participants). Study focused on early infancy period and may not capture later developmental changes. Methodology for defining 'enlarged' perivascular spaces not detailed in abstract. Long-term follow-up data beyond school-age not available.

Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume. To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep problems in later childhood.

This prospective, longitudinal cohort study used data from the Infant Brain Imaging Study. Magnetic resonance images were acquired at ages 6, 12, and 24 months (2007-2017), with sleep questionnaires performed between ages 7 and 12 years (starting in 2018). Data were collected at 4 sites in North Carolina, Missouri, Pennsylvania, and Washington. Data were analyzed from March 2021 through August 2022.

PVS (ie, fluid-filled channels that surround blood vessels in the brain) that are enlarged (ie, visible on magnetic resonance imaging). Outcomes of interest were enlarged PVS and EA-CSF volume from 6 to 24 months, autism diagnosis at 24 months, sleep problems between ages 7 and 12 years. A total of 311 infants (197 [63.3%] male) were included: 47 infants at high familial likelihood for autism (ie, having an older sibling with autism) who were diagnosed with autism at age 24 months, 180 high likelihood infants not diagnosed with autism, and 84 low likelihood control infants not diagnosed with autism. Sleep measures at school-age were available for 109 participants.

Of infants who developed autism, 21 (44.7%) had enlarged PVS at 24 months compared with 48 infants (26.7%) in the high likelihood but no autism diagnosis group (P = .02) and 22 infants in the control group (26.2%) (P = .03). Across all groups, enlarged PVS at 24 months was associated with greater EA-CSF volume from ages 6 to 24 months (β = 4.64; 95% CI, 0.58-8.72; P = .002) and more frequent night wakings at school-age (F = 7.76; η2 = 0.08; P = .006). These findings suggest that enlarged PVS emerged between ages 12 and 24 months in infants who developed autism. These results add to a growing body of evidence that, along with excessive CSF volume and sleep dysfunction, the glymphatic system could be dysregulated in infants who develop autism.