Traumatic brain injury (TBI) is the most prevalent brain disorder in Denmark, of which about 90% are classified as mild (mTBI). However, mTBI is far from trivial, carrying significant morbidity and profound socioeconomic consequences. Symptoms arising in the aftermath of head trauma are known as post-concussive symptoms and are present in about 30% of patients 3 to 6 months after mTBI, with sleep disturbances among the most prevalent. Disrupted sleep prolongs recovery time and contributes to other post-concussive symptoms such as cognitive complaints, headaches, and psychological distress. The pathophysiological mechanisms underlying these post-concussive symptoms remain poorly understood, hindering the development of effective treatment strategies.
The glymphatic system is a mechanism, which regulates the clearance of metabolic waste from the brain parenchyma. The glymphatic system is tightly coupled to sleep and electroencephalographic (EEG) slow waves, which increase the clearance of waste products, including amyloid-beta. Glymphatic dysfunction has been hypothesized to underlie the link between TBI and dementia and post-traumatic headache, and rodent studies have shown a decrease in glymphatic flow following TBI. Sleep is also believed to play a role in the consolidation of memory through coordinated activation of brain rhythms. The microstructural consequences of this interplay are complex, but is generally believed to be a decrease in synaptic strength. Recent studies suggest disruptions of these brain rhythms after TBI, but the consequences on cortical microstructure, memory consolidation, and cognitive function are yet to be determined.
Here, we propose that disruption of the sleep-wake cycle and the dysfunction of the glymphatic system and the coordination of brain rhythms may be a key mechanism contributing to prolonged post-concussive symptoms in patients with mTBI. The study is a prospective cohort study in which patients with mTBI are followed from the days following mTBI until 1 year after mTBI. One week and three months after mTBI, brain hydro- and hemodynamics are measured together with subjective and objective sleep measures. Trajectories of symptoms and cognitive performance will be related to sleep quality and brain hemo- and hydrodynamics, and the overall aim of the project is to predict the development of persisting symptoms from mTBI.
Assessments of sleep quality, brain oscillations, and brain microstructure in mTBI will aid our understanding of the pathogenesis of persistent post-concussive symptoms and may identify prognostic biomarkers for mTBI outcomes. Such knowledge would inform resource allocation and support the development of much-needed targeted treatments for persistent post-concussive symptoms.
Involved persons: Kristoffer Brendstrup-Brix.