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.

中文翻译：

---

中度至重度创伤性脑损伤的神经变性程度：系统评价方案。

背景我们对中度至重度创伤性脑损伤（TBI）后恢复的理解已经发生了变化。直到最近，人们还认为，在经历一段时期的急性神经系统脆弱性之后，大脑在慢性损伤阶段仍保持稳定。然而，最近的研究表明，中度至重度 TBI 的慢性阶段会出现神经退行性变，这对神经稳定性的假设提出了挑战。尽管有大量证据表明神经退行性病变的发生，但关于其规模和时间仍存在争议。本系统综述将评估中度至重度 TBI 成年患者神经退行性变的规模和时间线。方法 文献检索将在六个电子数据库（从建立之日起）中进行，包括 MEDLINE、EMBASE、PsycINFO、CINAHL、SportDiscus 和 Cochrane Central Register of Controlled Trials。我们将包括检查 TBI 患者单个样本中神经退行性变化的观察性研究，或比较 TBI 患者和健康对照之间的神经影像结果的研究。我们的主要结果是结构神经影像，次要结果是用于检测损伤后白质变化的扩散张量成像。所有筛选、数据提取和研究质量评估将由相同的两名研究成员独立执行。预计将产生文献的叙述性摘要。如果可行，我们将进行随机效应荟萃分析。然而，考虑到研究之间预期的异质性（例如，成像时间、成像区域），我们不期望进行荟萃分析；相反，预计将对我们的发现进行叙述性综合。讨论 了解中度至重度 TBI 中神经退行性变的规模和时间线（以及哪些大脑区域最容易遭受慢性衰退）可以为旨在抵消此类变化的干预研究提供信息。这可能有助于改善中度至重度 TBI 后的患者预后，进而减轻损伤负担。系统审查注册 PROSPERO CRD42019117548。