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Abstract
Background and Objectives Enlarged perivascular spaces (ePVS) have been identified as a key signature of glymphatic system dysfunction in neurologic conditions. The incidence and clinical implications of ePVS after traumatic brain injury (TBI) are not yet understood. We investigated whether individuals with chronic moderate-to-severe TBI had an increased burden of ePVS and whether ePVS burden is modulated by the presence of focal lesions, older brain age, and poorer sleep quality. We examined whether an increased burden of ePVS was associated with poorer cognitive and emotional outcomes.
Methods Using a cross-sectional design, participants with a single moderate-to-severe chronic TBI (sustained ≥10 years ago) were recruited from an inpatient rehabilitation program. Control participants were recruited from the community. Participants underwent 3T brain MRI, neuropsychological assessment, and clinical evaluations. ePVS burden in white matter was quantified using automated segmentation. The relationship between the number of ePVS, group membership, focal lesions, brain age, current sleep quality, and outcome was modeled using negative binomial and linear regressions.
Results This study included 100 participants with TBI (70% male; mean age = 56.8 years) and 75 control participants (54.3% male; mean age = 59.8 years). The TBI group had a significantly greater burden of ePVS (prevalence ratio rate [PRR] = 1.29, p = 0.013, 95% CI 1.05–1.57). The presence of bilateral lesions was associated with greater ePVS burden (PRR = 1.41, p = 0.021, 95% CI 1.05–1.90). There was no association between ePVS burden, sleep quality (PRR = 1.01, p = 0.491, 95% CI 0.98–1.048), and sleep duration (PRR = 1.03, p = 0.556, 95% CI 0.92–1.16). ePVS was associated with verbal memory (β = −0.42, p = 0.006, 95% CI −0.72 to −0.12), but not with other cognitive domains. The burden of ePVS was not associated with emotional distress (β = −0.70, p = 0.461, 95% CI −2.57 to 1.17) or brain age (PRR = 1.00, p = 0.665, 95% CI 0.99–1.02).
Discussion TBI is associated with a greater burden of ePVS, especially when there have been bilateral brain lesions. ePVS was associated with reduced verbal memory performance. ePVS may indicate ongoing impairments in glymphatic system function in the chronic postinjury period.
Glossary
- AQP4=
- aquaporin-4;
- ePVS=
- enlarged PVS;
- FLAIR=
- fluid-attenuated inversion recovery;
- GCS=
- Glasgow coma scale;
- GOSE=
- Glasgow Outcome Scale–Extended;
- MAPS=
- Multimodal Autoidentification of Perivascular Spaces;
- PRR=
- prevalence rate ratio;
- PSQI=
- Pittsburgh Sleep Quality Index;
- PTA=
- posttraumatic amnesia;
- PVS=
- perivascular space;
- TBI=
- traumatic brain injury;
- WTAR=
- Wechsler Test of Adult Reading
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Linda Hershey, MD, PhD, FAAN.
- Received November 7, 2022.
- Accepted in final form March 17, 2023.
- © 2023 American Academy of Neurology
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