Hawryluk, Gregory W. J.

Abstract Traumatic brain injury (TBI) can lead to chronic complications, including headache and facial hypersensitivity. Second-impact syndrome (SIS), occurring when a second TBI precedes recovery from an initial injury, often causes severe long-term symptoms. Neuroinflammation is implicated, but the comprehensive pathophysiology of SIS remains unclear. This study characterized neurological/behavioral outcomes, facial nociception, plasma inflammatory markers, and central nervous system (CNS) histopathology in rat models of SIS and single mild TBI. Female Wistar rats (n = 6/group) were assigned to naïve control, sham surgery, single impact (TBI), or double impact (SIS; intervals: 1h, 24h, 3d, 7d, 14d). Mild TBI was induced using a modified Marmarou weight-drop model. Assessments (facial mechanical sensitivity via von Frey, Neurological Severity Scale (NSS), Neurobehavioral Scale (NBS)) were performed pre-injury and on days 1,3,5,7 post-injury. Plasma IL-6 and TNF-α were measured by ELISA. Histopathology (H&E) assessed CNS inflammation. All impact groups developed transient facial mechanical allodynia and acute neurobehavioral deficits (impaired NSS/NBS at day 1). SIS groups, particularly with longer intervals (≥ 24h), exhibited more prolonged facial allodynia and significant neurological deficits compared to single TBI at specific timepoints. Plasma cytokines showed minimal changes. Histopathology revealed significantly elevated CNS inflammation in both TBI and SIS groups versus controls, with SIS groups (intervals 24h-14d) showing robust responses. Repeated TBI, especially with longer recovery intervals between injuries, results in more severe and prolonged facial allodynia, neurological deficits, and CNS neuroinflammation than a single mild TBI. These findings illuminate SIS pathophysiology and underscore the critical need for protection post-concussion.

Moderate traumatic brain injury (TBI) is a diagnosis that describes diverse patients with heterogeneity of primary injuries. Defined by a Glasgow Coma Scale between 9 and 12, this category includes patients who may neurologically worsen and require increasing intensive care resources and/or emergency neurosurgery. Despite the unique characteristics of these patients, there have not been specific guidelines published before this effort to support decision-making in these patients. A Delphi consensus group from the Latin American Brain Injury Consortium was established to generate recommendations related to the definition and categorization of moderate TBI. Before an in-person meeting, a systematic review of the literature was performed identifying evidence relevant to planned topics. Blinded voting assessed support for each recommendation. A priori the threshold for consensus was set at 80% agreement. Nine PICOT questions were generated by the panel, including definition, categorization, grouping, and diagnosis of moderate TBI. Here, we report the results of our work including relevant consensus statements and discussion for each question. Moderate TBI is an entity for which there is little published evidence available supporting definition, diagnosis, and management. Recommendations based on experts' opinion were informed by available evidence and aim to refine the definition and categorization of moderate TBI. Further studies evaluating the impact of these recommendations will be required.