ABSTRACT
BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. Recently, a paradigm shift in our understanding of moderate-to-severe TBI has led to its reconceptualization as a progressive neurodegenerative disorder. Widespread progressive atrophy is observed in the months and years post-injury, long after the acute effects of the injury have resolved. Some studies have begun to examine prognostic demographic, injury-related, and post-injury risk factors that contribute to these declines. A synthesis of this information, and in particular, an increased understanding of post-injury factors that may be modifiable, would improve our ability to design interventions to reduce neurodegeneration in moderate-to-severe TBI. This systematic review aims to identify prognostic factors for neural deterioration in moderate-to-severe TBI, and thereby inform future intervention research in this population. METHODS: This review protocol was informed by and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines. Search strategies (designed to identify literature on prognostic factors of neurodegeneration in adults with moderate-to-severe TBI) optimized for MEDLINE, EMBASE PsychINFO, CINAHL, SportDiscus, and Cochrane Central Register of Controlled Trials will be developed with the assistance of a health sciences librarian. Retrieved studies will be screened by two team members. Studies must report on longitudinal neuroimaging (i.e., two or more scans in the same cohort) or neuroimaging in a cross-sectional study and potential prognostic factors for neurodegeneration, such as demographics (e.g., gender, age, education), injury (e.g., severity, etiology), or post-injury characteristics (e.g., type and length of therapy, activity level, mood). DISCUSSION: By identifying prognostic factors for neurodegeneration, this systematic review can help inform injury management, as well as intervention research designed to offset the effects of modifiable prognostic factors, such as low levels of cognitive or physical activity. In turn, this systematic review can increase our understanding of how to improve outcome following moderate-to-severe TBI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122389.
Subject(s)
Brain Injuries, Traumatic/rehabilitation , Neurodegenerative Diseases , Prognosis , Humans , Neuroimaging , Risk Factors , Systematic Reviews as TopicABSTRACT
BACKGROUND: Our understanding of recovery after moderate-to-severe traumatic brain injury (TBI) has shifted. Until recently, it was presumed that following a period of acute neurological vulnerability, the brain remained stable in the chronic stages of injury. However, recent research has shown neurodegeneration in the chronic stages of moderate-to-severe TBI, challenging the assumption of neurological stability. While there is extensive evidence that neurodegeneration occurs, debate remains regarding the scale and timing. This systematic review will evaluate the scale and timelines of neurodegeneration in adult patients with moderate-to-severe TBI. METHODS: Literature searches will be conducted in six electronic databases (from inception onwards), including MEDLINE, EMBASE, PsycINFO, CINAHL, SportDiscus, and Cochrane Central Register of Controlled Trials. We will include observational studies that examine neurodegenerative changes within a single sample of TBI patients or studies that compare neuroimaging outcomes between TBI patients and healthy controls. Our primary outcome is structural neuroimaging, and our secondary outcome is diffusion tensor imaging for detection of post-injury white matter changes. All screening, data extraction, and study quality appraisal will be performed independently by the same two study members. It is expected that a narrative summary of the literature will be produced. If feasible, we will conduct a random-effects meta-analysis. However, given the expected heterogeneity between studies (with respect to, for example, timing of imaging, regions imaged) we do not expect to perform a meta-analysis; rather, a narrative synthesis of our findings is expected to be performed. DISCUSSION: Understanding the scale and timelines of neurodegeneration in moderate-to-severe TBI (as well as which brain areas are most vulnerable to chronic declines) can inform intervention research designed to offset such changes. This may help improve patient outcome following moderate-to-severe TBI and, in turn, reduce the burden of the injury. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019117548.
