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Medicina
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Traumatic Brain Injury: Current Efforts in Research and Clinical Care
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Traumatic Brain Injury: Current Efforts in Research and Clinical Care

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 21085

Special Issue Editor

Dr. John K. Yue

E-Mail Website
Guest Editor
Department of Neurosurgery, University of California, San Francisco, CA 94607, USA
Interests: traumatic brain injury; neurosurgery; neurotrauma; biomarkers; spinal cord injury; spine surgery; epidemiology; neuroimaging; outcomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Clinical care and research have been hampered by the lack of data standardization and outdated paradigms for classification and diagnosis. In recent years, there have been consensus efforts on data standardization across clinical and demographic data, biomarkers, genetics, neuroimaging, and outcomes research across multicenter approaches to validate diagnostic and prognostic approaches with adequate statistical power for conclusive evidence. Furthermore, TBI treatment is not a one-size-fits-all approach, and the classification, treatment, and prognosis of milder versus more severe injuries differ across this heterogeneous disease. In this Special Issue, we welcome submissions on the standardization of different forms of TBI data, creation of guidelines, and new paradigms of treatment, focusing on lesion type, location, volume, and other quantifiable markers of severity in the classification of different types and severities of TBI.

Special focus will also be granted to biomarker and neuroimaging studies that are sensitive and/or specific to TBI diagnosis or prognosis, and well as primary and secondary prevention of TBI across phenotypes and severities. With the studies of this Special Issue, we hope to create a compendium of work that will be informative for leaders of the field and continue to accelerate TBI research and clinical care from concussion to coma.

Dr. John K. Yue
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • data standardization
  • guidelines
  • traumatic brain injury
  • biomarkers
  • outcomes
  • classification
  • diagnosis
  • prognosis

Published Papers (8 papers)

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Research

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11 pages, 489 KiB  
Article
Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications?
by Gabriele Savioli, Iride Francesca Ceresa, Sabino Luzzi, Alice Giotta Lucifero, Maria Serena Pioli Di Marco, Federica Manzoni, Lorenzo Preda, Giovanni Ricevuti and Maria Antonietta Bressan
Medicina 2021, 57(4), 357; https://doi.org/10.3390/medicina57040357 - 07 Apr 2021
Cited by 15 | Viewed by 2464
Abstract
Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II [...] Read more.
Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient’s condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe. Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
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15 pages, 363 KiB  
Article
Rates of Intracranial Hemorrhage in Mild Head Trauma Patients Presenting to Emergency Department and Their Management: A Comparison of Direct Oral Anticoagulant Drugs with Vitamin K Antagonists
by Gabriele Savioli, Iride Francesca Ceresa, Sabino Luzzi, Cristian Gragnaniello, Alice Giotta Lucifero, Mattia Del Maestro, Stefano Marasco, Federica Manzoni, Luca Ciceri, Elia Gelfi, Giovanni Ricevuti and Maria Antonietta Bressan
Medicina 2020, 56(6), 308; https://doi.org/10.3390/medicina56060308 - 23 Jun 2020
Cited by 28 | Viewed by 3541
Abstract
Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. [...] Read more.
Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined; however, this result must take into account the very small number of patients needing surgery. Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
10 pages, 961 KiB  
Article
Association Between the Cerebral Autoregulation Index (Pressure Reactivity), Patient’s Clinical Outcome, and Quality of ABP(t) and ICP(t) Signals for CA Monitoring
by Basant K. Bajpai, Aidanas Preiksaitis, Saulius Vosylius and Saulius Rocka
Medicina 2020, 56(3), 143; https://doi.org/10.3390/medicina56030143 - 20 Mar 2020
Cited by 2 | Viewed by 1997
Abstract
Background and Objectives: The aim of this study was to explore the association between the cerebral autoregulation (CA) index, the pressure reactivity index (PRx), the patient’s clinical outcome, and the quality of arterial blood pressure (ABP(t)) and intracranial blood pressure (ICP(t)) signals [...] Read more.
Background and Objectives: The aim of this study was to explore the association between the cerebral autoregulation (CA) index, the pressure reactivity index (PRx), the patient’s clinical outcome, and the quality of arterial blood pressure (ABP(t)) and intracranial blood pressure (ICP(t)) signals by comparing two filtering methods to derive the PRx. Materials and Methods: Data from 60 traumatic brain injury (TBI) patients were collected. Moving averaging and FIR (Finite Impulse Response) filtering were performed on the ABP(t) and ICP(t) signals, and the PRx was estimated from both filtered datasets. Sensitivity, specificity, and receiver-operating characteristic (ROC) curves with the area under the curves (AUCs) were determined using patient outcomes as a reference. The outcome chosen for comparison among the two filtering methods were mortality and survival. Results: The FIR filtering approach, compared with clinical outcome, had a sensitivity of 70%, a specificity of 81%, and a level of significance p = 0.001 with an area under the curve (AUC) of 0.78. The moving average filtering method compared with the clinical outcome had a sensitivity of 58%, a specificity of 72%, and a level of significance p = 0.054, with an area under the curve (AUC) of 0.66. Conclusions: The FIR (optimal) filtering approach was found to be more sensitive for discriminating between two clinical outcomes, namely intact (survival) and impaired (death) cerebral autoregulation for TBI treatment decision making. Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
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10 pages, 2096 KiB  
Article
Bedside Sonographic Duplex Technique as a Monitoring Tool in Patients after Decompressive Craniectomy: A Single Centre Experience
by Habib Bendella, Joachim Spreer, Alexander Hartmann, Alhadi Igressa, Marc Maegele, Rolf Lefering and Makoto Nakamura
Medicina 2020, 56(2), 85; https://doi.org/10.3390/medicina56020085 - 19 Feb 2020
Cited by 1 | Viewed by 2029
Abstract
Background and objectives: Bedside sonographic duplex technique (SDT) may be used as an adjunct to cranial computed tomography (CCT) to monitor brain-injured patients after decompressive craniectomy (DC). The present study aimed to assess the value of SDT in repeated measurements of ventricle dimensions [...] Read more.
Background and objectives: Bedside sonographic duplex technique (SDT) may be used as an adjunct to cranial computed tomography (CCT) to monitor brain-injured patients after decompressive craniectomy (DC). The present study aimed to assess the value of SDT in repeated measurements of ventricle dimensions in patients after DC by comparing both techniques. Materials and Methods: Retrospective assessment of 20 consecutive patients after DC for refractory intracranial pressure (ICP) increase following subarachnoid hemorrhage (SAH), bleeding and trauma which were examined by SDT and CCT in the context of routine clinical practice. Whenever a repeated CCT was clinically indicated SDT examinations were performed within 24 hours and correlated via measurement of the dimensions of all four cerebral ventricles. Basal cerebral arteries including pathologies such as vasospasms were also evaluated in comparison to selected digital subtraction angiography (DSA). Results: Repeated measurements of all four ventricle diameters showed high correlation between CCT and SDT (right lateral r = 0.997, p < 0.001; left lateral r = 0.997, p < 0.001; third r = 0.991, p < 0.001, fourth ventricle r = 0.977, p < 0.001). SDT performed well in visualizing basal cerebral arteries including pathologies (e.g., vasospasms) as compared to DSA. Conclusions: Repeated SDT measurements of the dimensions of all four ventricles in patients after DC for refractory ICP increase delivered reproducible results comparable to CCT. SDT may be considered as a valuable bedside monitoring tool in patients after DC. Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
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Review

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16 pages, 1799 KiB  
Review
B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective
by Hansen Deng, John K. Yue, Benjamin E. Zusman, Enyinna L. Nwachuku, Hussam Abou-Al-Shaar, Pavan S. Upadhyayula, David O. Okonkwo and Ava M. Puccio
Medicina 2020, 56(6), 300; https://doi.org/10.3390/medicina56060300 - 18 Jun 2020
Cited by 21 | Viewed by 2551
Abstract
Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates [...] Read more.
Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates the clinical evidence on Bcl-2 and neurological recovery in patients after traumatic brain injury (TBI). Materials and Methods: All studies in English were queried from the National Library of Medicine PubMed database using the following search terms: (B-cell lymphoma 2/Bcl-2/Bcl2) AND (brain injury/head injury/head trauma/traumatic brain injury) AND (human/patient/subject). There were 10 investigations conducted on Bcl-2 and apoptosis in TBI patients, of which 5 analyzed the pericontutional brain tissue obtained from surgical decompression, 4 studied Bcl-2 expression as a biomarker in the cerebrospinal fluid (CSF), and 1 was a prospective randomized trial. Results: Immunohistochemistry (IHC) in 94 adults with severe TBI showed upregulation of Bcl-2 in the pericontusional tissue. Bcl-2 was detected in 36–75% of TBI patients, while it was generally absent in the non-TBI controls, with Bcl-2 expression increased 2.9- to 17-fold in TBI patients. Terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL) positivity for cell death was detected in 33–73% of TBI patients. CSF analysis in 113 TBI subjects (90 adults, 23 pediatric patients) showed upregulation of Bcl-2 that peaked on post-injury day 3 and subsequently declined after day 5. Increased Bcl-2 in the peritraumatic tissue, rising CSF Bcl-2 levels, and the variant allele of rs17759659 are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). Conclusions: Bcl-2 is upregulated in the pericontusional brain and CSF in the acute period after TBI. Bcl-2 has a neuroprotective role as a pro-survival protein in experimental models, and increased expression in patients can contribute to improvement in clinical outcomes. Its utility as a biomarker and therapeutic target to block neuronal apoptosis after TBI warrants further evaluation. Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
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17 pages, 591 KiB  
Review
The Role of Blood Biomarkers for Magnetic Resonance Imaging Diagnosis of Traumatic Brain Injury
by John K. Yue, Pavan S. Upadhyayula, Lauro N. Avalos, Hansen Deng and Kevin K. W. Wang
Medicina 2020, 56(2), 87; https://doi.org/10.3390/medicina56020087 - 22 Feb 2020
Cited by 27 | Viewed by 4889
Abstract
Background and Objectives: The annual global incidence of traumatic brain injury (TBI) is over 10 million. An estimated 29% of TBI patients with negative computed tomography (CT−) have positive magnetic resonance imaging (MRI+) findings. Judicious use of serum biomarkers with MRI may [...] Read more.
Background and Objectives: The annual global incidence of traumatic brain injury (TBI) is over 10 million. An estimated 29% of TBI patients with negative computed tomography (CT−) have positive magnetic resonance imaging (MRI+) findings. Judicious use of serum biomarkers with MRI may aid in diagnosis of CT-occult TBI. The current manuscript aimed to evaluate the diagnostic, therapeutic and risk-stratification utility of known biomarkers and intracranial MRI pathology. Materials and Methods: The PubMed database was queried with keywords (plasma OR serum) AND (biomarker OR marker OR protein) AND (brain injury/trauma OR head injury/trauma OR concussion) AND (magnetic resonance imaging/MRI) (title/abstract) in English. Seventeen articles on TBI biomarkers and MRI were included: S100 calcium-binding protein B (S100B; N = 6), glial fibrillary acidic protein (GFAP; N = 3), GFAP/ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1; N = 2), Tau (N = 2), neurofilament-light (NF-L; N = 2), alpha-synuclein (N = 1), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor peptide (AMPAR; N = 1). Results: Acute GFAP distinguished CT−/MRI+ from CT−/MRI− (AUC = 0.777, 0.852 at 9–16 h). GFAP discriminated CT−/diffuse axonal injury (DAI+) from controls (AUC = 0.903). Tau correlated directly with number of head strikes and inversely with white matter fractional anisotropy (FA), and a cutoff > 1.5 pg/mL discriminated between DAI+ and DAI− (sensitivity = 74%/specificity = 69%). NF-L had 100% discrimination of DAI in severe TBI and correlated with FA. Low alpha-synuclein was associated with poorer functional connectivity. AMPAR cutoff > 0.4 ng/mL had a sensitivity of 91% and a specificity of 92% for concussion and was associated with minor MRI findings. Low/undetectable S100B had a high negative predictive value for CT/MRI pathology. UCH-L1 showed no notable correlations with MRI. Conclusions: An acute circulating biomarker capable of discriminating intracranial MRI abnormalities is critical to establishing diagnosis for CT-occult TBI and can triage patients who may benefit from outpatient MRI, surveillance and/or follow up with TBI specialists. GFAP has shown diagnostic potential for MRI findings such as DAI and awaits further validation. Tau shows promise in detecting DAI and disrupted functional connectivity. Candidate biomarkers should be evaluated within the context of analytical performance of the assays used, as well as the post-injury timeframe for blood collection relative to MRI abnormalities. Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
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Other

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5 pages, 299 KiB  
Reply
Mild Head Trauma (MHT) and Antiplatelet Therapy. Reply to Lorenzati et al. Comment on “Savioli et al. Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications? Medicina 2021, 57, 357”
by Gabriele Savioli, Iride Francesca Ceresa, Sabino Luzzi, Alice Giotta Lucifero, Ginevra Cambiè, Federica Manzoni, Lorenzo Preda, Giovanni Ricevuti and Maria Antonietta Bressan
Medicina 2021, 57(9), 889; https://doi.org/10.3390/medicina57090889 - 27 Aug 2021
Cited by 5 | Viewed by 1423
Abstract
We read your data with interest, and we truly appreciate the similar experience [...] Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
2 pages, 205 KiB  
Comment
Comment on Savioli et al. Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications? Medicina 2021, 57, 357
by Bartolomeo Lorenzati, Alice Bruno, Giulia Racca, Jacopo Giamello, Attilio Allione, Letizia Barutta, Emanuele Bernardi, Ilaria Blangetti, Alessia Bono, Luca Dutto, Chiara Fulcheri, Remo Galaverna, Alberto Grosso, Elena Maggio, Gianpiero Martini, Vincenzo Peloponneso, Massimo Perotto, Tania Prinzis, Paola Ramonda, Alessandro Raviolo, Massimo Rega, Andrea Tortore, Francesco Tosello, Andrea Sciolla, Giuseppe Lauria and on behalf of “Trauma Management Course” Facultyadd Show full author list remove Hide full author list
Medicina 2021, 57(9), 887; https://doi.org/10.3390/medicina57090887 - 27 Aug 2021
Viewed by 1339
Abstract
We read the article of Savioli G. et al. [...] Full article
(This article belongs to the Special Issue Traumatic Brain Injury: Current Efforts in Research and Clinical Care)
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