scholarly journals Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeyu Wang ◽  
Haichen Wang ◽  
Ryan Becker ◽  
Joseph Rufo ◽  
Shujie Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Flow Cytometry ◽  
Brain Injury ◽  
Early Diagnosis ◽  
Tissue Injury ◽  
Management Strategies ◽  
Acoustic Properties ◽  
Early Management ◽  
Biomarker Analysis ◽  
Downstream Analysis

AbstractTraumatic brain injury (TBI) is a global cause of morbidity and mortality. Initial management and risk stratification of patients with TBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available, noninvasive diagnostic biomarker. In particular, a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild TBI (mTBI). Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue injury. By applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after TBI. Acoustofluidic isolation eliminated interference from other blood components, making it possible to detect exosomal biomarkers for TBI via flow cytometry. Flow cytometry analysis indicated that exosomal biomarkers for TBI increase in the first 24 h following head trauma, indicating the potential of using circulating exosomes for the rapid diagnosis of TBI. Elevated levels of TBI biomarkers were only detected in the samples separated via acoustofluidics; no changes were observed in the analysis of the raw plasma sample. This finding demonstrated the necessity of sample purification prior to exosomal biomarker analysis. Since acoustofluidic exosome separation can easily be integrated with downstream analysis methods, it shows great potential for improving early diagnosis and treatment decisions associated with TBI.

scholarly journals Early diagnosis of mortality using admission CT perfusion in severe traumatic brain injury patients (ACT-TBI): protocol for a prospective cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e047305
Author(s):  
Susan Alcock ◽  
Divjeet Batoo ◽  
Sudharsana Rao Ande ◽  
Rob Grierson ◽  
Marco Essig ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Early Diagnosis ◽  
Hospital Mortality ◽  
Brain Death ◽  
Severe Traumatic Brain Injury ◽  
Health Research ◽  
Ct Perfusion ◽  
Severe Tbi

IntroductionSevere traumatic brain injury (TBI) is a catastrophic neurological condition with significant economic burden. Early in-hospital mortality (<48 hours) with severe TBI is estimated at 50%. Several clinical examinations exist to determine brain death; however, most are difficult to elicit in the acute setting in patients with severe TBI. Having a definitive assessment tool would help predict early in-hospital mortality in this population. CT perfusion (CTP) has shown promise diagnosing early in-hospital mortality in patients with severe TBI and other populations. The purpose of this study is to validate admission CTP features of brain death relative to the clinical examination outcome for characterizing early in-hospital mortality in patients with severe TBI.Methods and analysisThe Early Diagnosis of Mortality using Admission CT Perfusion in Severe Traumatic Brain Injury Patients study, is a prospective cohort study in patients with severe TBI funded by a grant from the Canadian Institute of Health Research. Adults aged 18 or older, with evidence of a severe TBI (Glasgow Coma Scale score ≤8 before initial resuscitation) and, on mechanical ventilation at the time of imaging are eligible. Patients will undergo CTP at the time of first imaging on their hospital admission. Admission CTP compares with the reference standard of an accepted bedside clinical assessment for brainstem function. Deferred consent will be used. The primary outcome is a binary outcome of mortality (dead) or survival (not dead) in the first 48 hours of admission. The planned sample size for achieving a sensitivity of 75% and a specificity of 95% with a CI of ±5% is 200 patients.Ethics and disseminationThis study has been approved by the University of Manitoba Health Research Ethics Board. The findings from our study will be disseminated through peer-reviewed journals and presentations at local rounds, national and international conferences. The public will be informed through forums at the end of the study.Trial registration numberNCT04318665

scholarly journals Automatic EEG processing for the early diagnosis of Traumatic Brain Injury

2016 ◽  
Author(s):  
Bruno Albert ◽  
Jingjing Zhang ◽  
Alexandre Noyvirt ◽  
Rossitza Setchi ◽  
Haldor Sjaaheim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Early Diagnosis

Risk factors and early diagnosis of cerebral venous sinus occlusion secondary to traumatic brain injury

2015 ◽  
Vol 63 (6) ◽  
pp. 881 ◽  
Author(s):  
Shousen Wang ◽  
Jun Li ◽  
Liangfeng Wei ◽  
Bingyang Xu ◽  
Xiaojun Zhang
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Early Diagnosis ◽  
Venous Sinus

scholarly journals Hyponatremia in the Neurologically Ill Patient: A Review

2020 ◽  
Vol 10 (3) ◽  
pp. 208-216
Author(s):  
David P. Lerner ◽  
Starane A. Shepherd ◽  
Ayush Batra
Keyword(s):  
Traumatic Brain Injury ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Early Diagnosis ◽  
Neurological Disorders ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Treatment Strategies ◽  
Diagnosis And Treatment ◽  
Systemic Complications ◽  
Acute Presentation

Hyponatremia is a well-known disorder commonly faced by clinicians managing neurologically ill patients. Neurological disorders are often associated with hyponatremia during their acute presentation and can be associated with specific neurologic etiologies and symptoms. Patients may present with hyponatremia with traumatic brain injury, develop hyponatremia subacutely following aneurysmal subarachnoid hemorrhage, or may manifest with seizures due to hyponatremia itself. Clinicians caring for the neurologically ill patient should be well versed in identifying these early signs, symptoms, and etiologies of hyponatremia. Early diagnosis and treatment can potentially avoid neurologic and systemic complications in these patients and improve outcomes. This review focuses on the causes and findings of hyponatremia in the neurologically ill patient and discusses the pathophysiology, diagnoses, and treatment strategies for commonly encountered etiologies.

scholarly journals Highly Sensitive Single Molecular Array Immunoassay Measurement of t-Tau, NF-L, GFAP, and UCH-L1 Biomarkers in Acute Concussion/Mild Traumatic Brain Injury (mTBI) Patient Serum and Saliva Samples

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S19.3-S20
Author(s):  
Ahmed Chenna ◽  
Christos Petropoulos ◽  
John Winslow
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Limited Information ◽  
Post Injury ◽  
Time Points ◽  
Highly Sensitive ◽  
Biomarker Analysis ◽  
T Tau ◽  
Control Samples

ObjectiveTo determine if t-Tau, NF-L, GFAP and UCH-L1 protein biomarkers are elevated in early time points of acute concussion/mild traumatic brain injury patient serum and saliva, relative to control samples.Backgroundt-Tau, NF-L, GFAP and UCH-L1 levels have been reported to increase in cerebral spinal fluid (CSF) and blood following head trauma within 24 hours or longer, and are candidate diagnostic and prognostic biomarkers of concussion and mild to moderate TBI. However, limited information exists on the relationship between these biomarkers at short time points post-injury, and detectability in saliva of mTBI patients.Design/MethodsBiomarker analysis of serum from a total of 120 participants, derived from two independent sample groups consisting of 60 concussion/mTBI patients each, with blood collected within 1-4 hr and 8-16 hr post-injury, respectively, was compared with 30 healthy control sera. Saliva samples were collected after 8-16 hr post-injury from a n = 30 subset of the same patients. Quanterix Simoa 4-plex immunoassay was used for highly sensitive measurements of these biomarkers.ResultsMedian levels of NF-L, GFAP and UCH-L1 were significantly higher in independent sets of patient serum samples (n = 60 each), both at early (1–4 hr) and later (8–16 hr) time points post-mTBI/concussion, relative to control samples (n = 30) (p < 0.0001, = 0.0001, <0.0001, respectively). Low levels of t-Tau are detected, but are significantly elevated post-concussion relative to controls (p = 0.0001). Significant correlations were observed between levels of t-Tau and UCH-L1, NF-L and GFAP, and t-Tau and GFAP in both post-injury time-point groups, and between NF-L and UCH-L1 levels in the 8-16 hr group. The four biomarkers were detected in saliva from concussion/mTBI patients (n = 30).ConclusionsThis study supports the utility of ultra-sensitive multiplex immunoassays to detect increases in CNS proteins at high sensitivity in serum and saliva within 1-4 and 8-16 hr of concussion/mTBI.

scholarly journals Dynamics of cerebrospinal fluid levels of matrix metalloproteinases in human traumatic brain injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Karolina Minta ◽  
Gunnar Brinkmalm ◽  
Faiez Al Nimer ◽  
Eric P. Thelin ◽  
Fredrik Piehl ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Matrix Metalloproteinases ◽  
Clinical Outcomes ◽  
Extracellular Enzymes ◽  
Tissue Injury ◽  
Normal Pressure ◽  
Magnetic Bead ◽  
Contrast Group

Abstract Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood–brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001–0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002–0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes.

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