Return to Work Within Four Months of Grade 3 Diffuse Axonal Injury

Neuroprognostication following diffuse axonal injury (DAI) has historically relied on neuroimaging techniques with lower spatial resolution and contrast than techniques currently available in clinical practice. Since the initial studies of DAI classification and prognosis in the 1980s and 1990s, advances in neuroimaging have improved detection of brainstem microbleeds, a hallmark feature of Grade 3 DAI that has traditionally been associated with poor neurologic outcome. Here, we report clinical and radiologic data from two patients with severe traumatic brain injury and grade 3 DAI who recovered functional independence and returned to work within 4 months of injury. Importantly, both patients were scanned using 3 Tesla MRI protocols that included susceptibility-weighted imaging (SWI), a technique that provides enhanced sensitivity for detecting brainstem microbleeds. These observations highlight the importance of developing approaches to DAI classification and prognosis that better align with contemporary neuroimaging capabilities.

Biomarkers to aid the return to play decision following sports-related concussion: a systematic review

Premature return to play (RTP) following sports-related concussion (SRC) is associated with significant morbidity including risk of neurological and non-neurological injury, persistent post-concussion symptoms and chronic neurological deficits. Assessing athletes for RTP is critical but these decisions are currently based on clinical assessments that are subject to bias and symptomatic reporting that rely on compliance. An objective and easily obtained biomarker that can indicate recovery following SRC would aid clinicians to make safer RTP decisions. We performed a systematic review to identify potential biomarkers from saliva, urine and blood sources that could inform the clinical RTP decision. The MEDLINE database was searched. Inclusion criteria were studies focusing on adults diagnosed with SRC, fluid biomarkers from blood, saliva or urine and clinical recovery from SRC or at RTP. We assessed each biomarker for their time course post SRC and relationship to clinical recovery. Secondary outcomes included correlation with symptom scores and predictive value for prolonged RTP. We identified 8 studies all investigating blood-based markers of diffuse axonal injury (tau, NFL, SNTF), neuroglial injury (NSE, VLP-1, UCH-L1, S100B, GFAP), inflammation and hormonal disturbances. Tau, SNTF, UCH-1, GFAP, S100B and the inflammatory cytokine MCP-4 are raised post SRC and return to baseline by RTP. Changes in tau, NFL, SNTF, GFAP and MCP-4 post SRC correlate with severity of concussion as measured by symptom severity or RTP duration. There is only preliminary case-reporting for hormonal biomarkers. The evidence is limited by a lack of highly powered studies, variation in use of athletic and Contact sport controls (CSC) and a lack of consistent sampling and assessment protocols. There is promise for biomarkers to aid RTP decisions following SRC, most notably in use alongside clinical assessment in RTP criteria to allow greater precision in identifying mild and severe concussion.

Delayed Diplopia After Sports-Related Concussion: A Multidisciplinary Approach to Evaluation and Management

ObjectiveTo highlight a multidisciplinary approach to the diagnosis and management of unilateral abducens palsy after a sports-related concussion.BackgroundMild traumatic brain injury (TBI) often leads to disruptions in visual functioning, affecting convergence, saccades, smooth pursuit, and accommodation. More severe TBI injuries may result in structural injuries to the ocular muscles, nerves, or the brain itself.Design/MethodsNA.ResultsCase: We present the case of a 33-year-old male with unilateral abducens nerve palsy after a sports-related concussion with loss of consciousness and multiple hemorrhagic contusions. The patient's visual symptoms manifested several days after the injury. With a multi-disciplinary evaluation involving specialists representing neurosurgery, endovascular neurology and neuro-ophthamology, unenhanced magnetic resonance imaging revealed multiple foci of intraparenchymal microhemorrhages and siderosis consistent with diffuse axonal injury (DAI), and an incidental parasagittal cavernoma. The delayed development of a sixth nerve palsy raised our suspicion for secondary axotomy, as has been described following TBI. While the probability of recovery is high, close follow up is imperative to address evolution of the patient's symptoms. In this case, the patient developed imbalance and headaches in association with his visual symptoms. For the imbalance we use physical therapy with therapists trained in vestibular therapy and for the visual symptoms we use vision therapy with trained optometrists.ConclusionsDelayed post-traumatic abducens palsy is concerning for DAI and secondary axotomy. Multidisciplinary assessment imparts the ability to evaluate for all possible causes and provide additional specialized care for recovery.

Neutrophil Extracellular Traps Facilitate Sympathoexcitation After Traumatic Brain Injury Via HMGB1/AP1 Signaling Pathway

Background: Traumatic brain injury (TBI) usually accompanies with sympathetic excitation, and paradoxical sympathetic hyperactivity (PSH) may be detrimental to the prognosis of TBI sufferers. Neutrophils can form neutrophil extracellular traps (NETs) to get involved in the neuroinflammation after TBI. As an important form of NETs, HMGB1 were found to activate the expression of AP1, which can increase the formation of IL-1β in microglia. Considering that IL-1β is able to regulate sympathoexcitation, it is reasonable to infer that HMGB1/AP1 signaling plays an important role in sympathoexcitation after TBI. Methods: In this present study, rat model with diffuse axonal injury (DAI) was established. The existance of NETs and the expression level of HMGB1/AP1/IL-1β in the paraventricular nucleus (PVN) after DAI were examined by immunofluorescence and Western blot (WB). The role of HMGB1/AP1 in the activation of microglia, secretion of IL-1β and sympathoexcitaiton were identified in vitro. Moreover, stereotaxic injection of anti-HMGB1 or HMGB1 was conducted to further validate the effect of HMGB1/AP1 pathway on sympathoexcitation after TBI.Results: The indicators of sympathoexcitation, including mean arterial pressure and serum catecholamine, increased and peaked at 72 hours after TBI. The formation of NETs was observed in PVN after injury, whereas, no NETs were found in the control group. And meanwhile, levels of NETs in PVN were higher than that in the para-PVN tissues after the injury. In vitro experiments showed that HMGB1 can promote the activation of microglia as well as increase the expression of AP1 and IL-1β. In vivo experiments suggested HMGB1 have an impact on the expression of AP1 and IL-1β in the PVN, and further controlling the sympathoexcitation after TBI.Conclusion: NETs might mediate sympathoexcitation after TBI through microglial activation in the PVN in a HMGB1/AP1/IL-1β dependent way.

17α-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial

Background Traumatic brain injury (TBI) and severe blood loss resulting in hemorrhagic shock (HS) represent leading causes of trauma-induced mortality, especially when co-occurring in pre-hospital settings where standard therapies are not readily available. The primary objective of this study was to determine if 17α-ethinyl estradiol-3-sulfate (EE-3-SO4) increases survival, promotes more rapid cardiovascular recovery, or confers neuroprotection relative to Placebo following TBI + HS. Methods All methods were approved by required regulatory agencies prior to study initiation. In this fully randomized, blinded preclinical study, eighty (50% females) sexually mature (190.64 ± 21.04 days old; 28.18 ± 2.72 kg) Yucatan swine were used. Sixty-eight animals received a closed-head, accelerative TBI followed by removal of approximately 40% of circulating blood volume. Animals were then intravenously administered EE-3-SO4 formulated in the vehicle at 5.0 mg/mL (dosed at 0.2 mL/kg) or Placebo (0.45% sodium chloride solution) via a continuous pump (0.2 mL/kg over 5 min). Twelve swine were included as uninjured Shams to further characterize model pathology and replicate previous findings. All animals were monitored for up to 5 h in the absence of any other life-saving measures (e.g., mechanical ventilation, fluid resuscitation). Results A comparison of Placebo-treated relative to Sham animals indicated evidence of acidosis, decreased arterial pressure, increased heart rate, diffuse axonal injury and blood–brain barrier breach. The percentage of animals surviving to 295 min post-injury was significantly higher for the EE-3-SO4 (28/31; 90.3%) relative to Placebo (24/33; 72.7%) cohort. EE-3-SO4 also restored pulse pressure more rapidly post-drug administration, but did not confer any benefits in terms of shock index. Primary blood-based measurements of neuroinflammation and blood brain breach were also null, whereas secondary measurements of diffuse axonal injury suggested a more rapid return to baseline for the EE-3-SO4 group. Survival status was associated with biological sex (female > male), as well as evidence of increased acidosis and neurotrauma independent of EE-3-SO4 or Placebo administration. Conclusions EE-3-SO4 is efficacious in promoting survival and more rapidly restoring cardiovascular homeostasis following polytraumatic injuries in pre-hospital environments (rural and military) in the absence of standard therapies. Poly-therapeutic approaches targeting additional mechanisms (increased hemostasis, oxygen-carrying capacity, etc.) should be considered in future studies.