Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts.

Objective: The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes. Methods: This pilot study comprised two independent cohorts. The first cohort-part of a Traumatic Head Injury Neuroimaging Classification (THINC) study-with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort-with a mean age of 19 years-comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay. Results: Concentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690-0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT-/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT-/MRI-, n = 111) findings and UIC (P-values < 0.05). Conclusion: These findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI.

OBJECTIVES: To determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI). METHODS: Study participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology. RESULTS: Concentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (p's < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90-0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70-0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69-0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT. CONCLUSION: Our study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials. CLASSIFICATION OF EVIDENCE: Class I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.

Sex differences in cerebral ischemia: possible molecular mechanisms.

Sex is emerging as an important factor in the etiology and expression of many different pathological conditions, including stroke. Initially, the levels of sex hormones were thought to be the major contributor to these sex differences, especially after puberty, when gonadal steroid levels sharply diverge between the sexes. More recently, it is recognized that sex differences also result from the organizational effects of sex hormone exposure early in development, even in the absence of hormone exposure later in life, as well as effects mediated by the sex chromosomes themselves. Epigenetic modifications of developmental genes important in sexual differentiation and the response to sex steroid hormones are also emerging as another important contributor to sex differences in disease expression. This review describes recent research on the relationship between hormones, organizational-activational effects of gonadal steroids, and epigenetic modifications in brain pathology, focusing specifically on cerebral ischemia.

Superficial siderosis: a case report and review of the literature.

BACKGROUND: A 48-year-old man with a past history of a car-accident-induced coma at the age of 3 years and spontaneous bilateral subdural hematomas at the age of 34 years presented with a 2-year history of worsening gait difficulties, clumsiness and dysarthria. CT scans of the brain taken during the 6 months leading up to his presentation had revealed chronic subarachnoid hemorrhage, but angiograms had not been able to identify the source of bleeding. INVESTIGATIONS: Neurological examination, brain MRI scan, lumbar puncture, four-vessel cerebral angiogram and spinal angiogram. DIAGNOSIS: Superficial siderosis; a complete review of the current literature on the condition is provided. MANAGEMENT: Iron chelating agents.