Brain dysfunction underlying prolonged post-concussive syndrome: A systematic review

Background: One out of 4 patients who sustains a mild traumatic brain injury (mTBI) experiences persistent complaints, despite the absence of structural brain damage on conventional neuroimaging. Susceptibility to develop post concussive symptoms (PCS) is thought to originate from occult brain dysfunction. However, the influence of such neural changes on the development of persistent PCS is poorly characterized. Methods: In this article, we aim to integrate findings from longitudinal studies that investigated across the spectrum of neuroimaging modalities the changes within the first twelve months following a mTBI, with the goal of identifying possible predictors or biomarkers of persistent PCS. Results: Nine studies met inclusion criteria: 5 that used resting state functional MRI, 2 that used Diffusion Weighted Imaging, and 2 that used ¹H-MR Spectroscopy. All studies indicate significant structural, functional and/or metabolic aberrations that occur in the acute and early subacute phases following a mTBI. However, in patients with persistent PCS, these mTBI-induced damages linger and relate to the severity of PCS. These biomarkers include: decreased diffusion along white matter fiber tracts, alteration of perfusion, disrupted metabolism, and reduced connectivity within several resting state networks. Additionally, in PCS patients, disruptions of brain function can manifest exclusively in the chronic phase. Conclusion: This review support the ongoing use of neuroimaging modalities to understand the brain changes that occur throughout the time course of mTBI. Based on the complexity of mTBI, however, more work is required to characterize injury and recovery mechanisms that could impact the emergence and persistence of PCS.