Associate Professor Department of Neurology, USU Bethesda, Maryland
Abstract Text:
Background: Sleep disorders such as insomnia are common after TBI and associated with worsened TBI outcomes. Unfortunately, little is known about how to identify individuals after TBI who are likely to require targeted sleep treatment. Blood biomarkers of brain injury and inflammation, such as glial fibrillary acidic protein (GFAP), have been shown to have a positive correlation with TBI severity, predicting lesions on head CT or MRI after injury. In a small cross-sectional study, we previously demonstrated that sleep quality is correlated with blood biomarkers of inflammation and brain injury. Yet, despite the increasing evidence of a link between inflammation and sleep, scant evidence has examined the association between blood biomarkers and sleep-related outcomes after TBI. In the largest population studied to date, we prospectively examined the association between acute plasma biomarkers and 12-month insomnia trajectories membership after TBI, hypothesizing that the known markers of more-severe brain injury, such as glial fibrillary acidic protein (GFAP) would predict worse 12-month insomnia trajectories.
Methods: Prospective data was from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. Participants (N=2,022) were enrolled within 24 hours of TBI and classified into insomnia trajectories based on latent class models of the Insomnia Severity Index at 2 weeks, 3-, 6-, and 12-months post-injury. GFAP, C-reactive protein (CRP), S100b, neuron specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolyase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. Multinomial logistic regression models were used to assess the association between biomarkers and 12-month insomnia trajectory membership.
Results: Surprisingly, D1 GFAP was lower in participants with persistent severe insomnia (median (Q1, Q3): 154 (19, 445) pg/mL) compared to resolving mild (491 (154, 1423), p< 0.001) and persistent mild (344 (79, 1287), p< 0.001) insomnia. D14 GFAP was similarly lower in severe insomnia participants. Higher D1 GFAP levels were associated with reduced odds of persistent severe (OR = 0.76 (95%CI: 0.63, 0.92), p =0.004) and persistent mild (OR = 0.88 (0.81, 0.96), p =0.003) compared to mild resolving insomnia. Furthermore, elevations in D1 CRP were associated with persistent insomnia severe (OR = 1.33 (1.11, 1.59), p=0.002) and persistent mild (OR = 1.10 (1.02, 1.19), p=0.011). D14 CRP elevations were similarly associated with persistent insomnia. No differences were found with other biomarkers.
Discussion: Our study is the first to evaluate associations between acute blood biomarkers and 12-month prospective trajectories of insomnia in a large population of TBI patients, presenting evidence supporting a novel role for biomarkers of neurodegeneration and inflammation in sleep health. Acute plasma biomarker concentrations showed that higher levels of hsCRP were associated with more severe trajectories of insomnia, and higher levels of GFAP were associated with milder trajectories of insomnia. These findings merit replication and, if they hold true, suggest that GFAP and hsCRP may have utility for predicting clinical need for targeted insomnia therapy. They also suggest that GFAP might not simply be a marker of TBI severity and might have a more complicated relationship with post-TBI symptoms. Further work will be needed to determine if lower GFAP levels are truly related to the maladaptive phenotype.
Funding: United States Congressionally Directed Medical Research Program.