Alzheimer’s disease marker phospho-tau181 is not elevated in the first year after moderate-severe TBI

Background: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer’s disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. Methods: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer’s disease, with healthy controls. Results: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer’s disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. Conclusions: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration

Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI

BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

No abstract available

Ventriculolumbar perfusion and inhalational anesthesia with sevoflurane in an accidental intrathecal injection of tranexamic acid: unreported treatment options

BackgroundTranexamic acid (TXA) decreases hemorrhage-related mortality in trauma patients and is increasingly being used during obstetric and orthopedic surgeries. Inadvertent intrathecal injection of TXA is a rare, potentially lethal event leading to dose-dependent cardiotoxicity and neurotoxicity. TXA enhances neuronal excitation by antagonizing inhibitory γ-aminobutyric acid type A and glycine receptors. Until now, mechanistic-based pharmacological treatments targeting multiple central nervous system receptors have been advocated for use in such cases, with no data on intrathecal TXA elimination techniques.Case presentationA patient scheduled for hip surgery accidentally received 350 mg of intrathecal TXA instead of levobupivacaine. The clinical picture progressed from spinal segmental myoclonus to generalized convulsions and malignant arrhythmias. The treatment consisted of ventriculolumbar perfusion with normal saline at a rate of 50 mL/hour starting 5 hours after TXA administration and inhalational sedation with sevoflurane, in addition to drugs acting on multiple receptors at different central nervous system levels. Over 2 months the neurological status improved, although it was not complete.ConclusionsFor the first time, the feasibility and possible clinical efficacy of combined treatment with ventriculolumbar perfusion and inhalational sedation with sevoflurane were demonstrated. A referral to a neurosurgical facility is recommended in patients with acute TXA-induced neurotoxicity and cardiotoxicity.</jats:sec

Successful Outcome of Inhalation Injury, Active SARS-CoV-2 Infection, and Concomitant Pneumonia in a Patient With 27% Full-Thickness Burn: A Case Report

Abstract Burn injuries are a major cause of morbidity and mortality. Next to the inhalation injury, TBSA and age are strong predictors of mortality in burn victims. The novel coronavirus disease 2019 (COVID-19) pandemic is associated with a fatality rate of around 3.5%. We present a case of burn victim with full-thickness burn to face, scalp, both upper extremities (27% of TBSA), inhalation injury, and active severe acute respiratory syndrome coronavirus 2 infection with concomitant pneumonia. The inhalation injury in COVID-19 positive patient was severe. A bronchoscopy revealed a diffuse erythema of the trachea and both main bronchi, the whole bronchial tree up to the distal segments was covered with carbonaceous material which could not be removed. We decided to treat the inhalation injury according to the guidelines for burns and acute respiratory distress syndrome. Accordingly, the patient did not receive any antiviral drugs or corticosteroids. The reconstruction of a full-thickness scalp defect after burn presents a challenge in large size defects and in patients with comorbidities. Double layer Integra Dermal Regeneration Template (Integra LifeSciences, Plainsboro, New Jersey) was the reconstruction method of choice. The take of dermal template and split-thickness skin graft was 100% and good scalp contour was achieved. To our knowledge this is the first case report presenting a successful treatment outcome in a burn victim with inhalation injury, active severe acute respiratory syndrome coronavirus 2 infection, and concomitant pneumonia with full-thickness burn of 27% of TBSA.</jats:p