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Traumatic Brain Injury (TBI): Clinical Updates and Perspectives

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Brain Injury".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 19017

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Dr. Anna Antoni

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Guest Editor

Department of Orthopedics and Trauma-Surgery, Medical University of Vienna, 1090 Vienna, Austria
Interests: polytrauma; traumatic brain injury; pelvis and acetabulum fractures

Special Issue Information

Dear Colleagues,

Traumatic brain injury (TBI) causes a high number of deaths, disabilities and impairments worldwide. TBI of all grades mandates the cooperation of various medical fields. Emergency medicine, anaesthesia, trauma surgery, neurosurgery, radiology, neurology, psychiatry, rehabilitation and other fields must collaborate to achieve good outcomes. Hence, this Special Issue, titled "Traumatic Brain Injury (TBI): Clinical Updates and Perspectives", aims to provide an overview of the latest advancements and future perspectives in the specialties involved in the management of TBI.

This Special Issue focuses on various aspects of TBI, including diagnosis, prognosis, management (surgical and non-surgical) and rehabilitation:

Guidelines for the management of mild TBI, TBI and antithrombotic therapy, imaging for TBI;
Multimodal neuromonitoring;
Artificial intelligence;
Surgical techniques;
Neurocognitive impairment after TBI;
Biomarkers;
Rehabilitation after experiencing TBI;
Other clinical updates and perspectives related to the field of TBI.

We are inviting researchers to submit their original research or review papers related to these areas. By doing so, you will contribute to the evaluation of current approaches and advancement of management strategies for TBI.

Dr. Anna Antoni
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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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 2600 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

traumatic brain injury
mild traumatic brain injury
moderate traumatic brain injury
severe traumatic brain injury
concussion
rehabilitation
guidelines

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Published Papers (9 papers)

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Research

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15 pages, 1863 KiB

Open AccessArticle

Blood-Based Lateral-Flow Immunoassays Dipstick Test for Damaged Mitochondrial Electron Transport Chain in Pyruvate Treated Rats with Combined Blast Exposure and Hemorrhagic Shock

by Evans Okonkwo, Biswajit Saha, Geetaram Sahu, Alakesh Bera and Pushpa Sharma

J. Clin. Med. 2025, 14(3), 754; https://doi.org/10.3390/jcm14030754 - 24 Jan 2025

Cited by 1 | Viewed by 716

Abstract

Blast trauma presents a unique challenge due to its complex mechanism of injury, which impacts the brain and other vital organs through overpressure waves and internal bleeding. Severe blood loss leads to an inadequate oxygen supply and insufficient fuel delivery to cells, impairing ATP production by mitochondria—essential for cell survival. While clinical symptoms of metabolic disruption are evident soon after injury, the molecular, cellular, and systemic damage persists for days to years post-injury. Current challenges in treating traumatic brain injury (TBI) stem from (1) the lack of early blood-based biomarkers for detecting metabolic failure and mitochondrial damage and (2) the limited success of mitochondrial-targeted therapeutic strategies. Objectives: To identify blood-based mitochondrial biomarkers for evaluating the severity of brain injuries and to investigate therapeutic strategies targeting mitochondria. Methods: A preclinical rat model subjected to blast exposure, with or without hemorrhagic shock (HS), followed by resuscitation was utilized. Blood samples were obtained at baseline (T0), post-injury (T60), and at the conclusion of the experiment (T180), and analyzed using a validated dipstick assay to measure mitochondrial enzyme activity. Results: Blast and HS injuries led to a significant decrease in the activity of mitochondrial enzymes, including complex I, complex IV, and the pyruvate dehydrogenase complex (PDH), compared to baseline (p < 0.05). Concurrently, blood lactate concentrations were significantly elevated (p < 0.001). An inverse correlation was observed between mitochondrial enzyme dysfunction and blood lactate levels (p < 0.05). Treatment with sodium pyruvate post-injury restored complex I, complex IV, and PDH activity to near-baseline levels, corrected hyperlactatemia, and reduced reactive oxygen species (ROS) production by mitochondria. Conclusions: Serial monitoring of blood mitochondrial enzyme activity, such as complex I, complex IV, and PDH, may serve as a valuable tool for prognostication and guiding the use of mitochondrial-targeted therapies. Additionally, mitochondrial enzyme assays in blood samples can provide insights into the global redox status, potentially paving the way for novel therapeutic interventions in TBI. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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25 pages, 1966 KiB

Open AccessArticle

Symptom Persistence Relates to Volume and Asymmetry of the Limbic System after Mild Traumatic Brain Injury

by Cheryl Vanier, Priya Santhanam, Nicholas Rochester, Lauren Carter, Mike Lim, Amir Kilani, Shivani Venkatesh, Sherwin Azad, Thomas Knoblauch, Tapasya Surti, Colin Brown, Justin Roy Sanchez, Leon Ma, Shaunaq Parikh, Leo Germin, Enrico Fazzini and Travis H. Snyder

J. Clin. Med. 2024, 13(17), 5154; https://doi.org/10.3390/jcm13175154 - 30 Aug 2024

Cited by 1 | Viewed by 1731

Abstract

Background: Persistent symptoms have been reported in up to 50% of the 27 million people with mild traumatic brain injuries (mTBI) every year. MRI findings are currently limited by low diagnostic and prognostic sensitivities, constraining the value of imaging in the stratification of patients following mTBI. Limbic system structures are promising brain regions in offering prognostic factors for symptom persistence following mTBI. The objective of this study was to associate volume and symmetry of limbic system structures with the presence and persistence of common symptoms in patients with mTBI. Methods: This study focused on 524 adults (aged 18–82), 58% female, with 82% injured in motor vehicle accidents and 28% reporting loss of consciousness (LOC). Magnetic resonance imaging (MRI) data included a sagittal 3D T1-weighted sequence with 1.2 mm slice thickness, with voxel sizes of 0.93 mm × 0.93 mm × 1.2 mm, obtained a median of 156 days after injury. Symptom diagnosis and persistence were collected retrospectively from patient medical records. Intracranial volume-adjusted regional volumes per side utilizing automated volumetric analysis (NeuroQuant^®) were used to calculate total volume, laterality index, and side-independent asymmetry. Covariates included age, sex, LOC, and days from injury. Limbic volumetrics did not relate to symptom presentation, except the (-) association between headache presence and thalamus volume (adjusted odds ratio = 0.51, 95% confidence interval = 0.32, 0.85). Headache, balance problems, anxiety, and depression persistence was (-) associated with thalamus volume (hazard ratio (HR) 1.25 to 1.94). Longer persistence of balance problems was associated with (-) lateral orbitofrontal cortex volume (HR = 1.33) and (+) asymmetry of the hippocampus (HR = 0.27). Persistence of cognitive deficits was associated with (+) asymmetry in the caudal anterior cingulate (HR = 0.67). Depression persistence was associated with (+) asymmetry in the isthmus of the cingulate gyrus (HR = 5.39). Persistence of anxiety was associated with (-) volume of the parahippocampal gyrus (HR = 1.67), orbitofrontal cortex (HR > 1.97), and right-biased laterality of the entorhinal cortex (HR = 0.52). Conclusions: Relative volume and asymmetry of the limbic system structures in patients with mTBI are associated with the persistence of symptoms, particularly anxiety. The conclusions of this study are limited by the absence of a reference group with no mTBI. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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13 pages, 618 KiB

Open AccessArticle

Differences in Eotaxin Serum Levels between Polytraumatized Patients with and without Concomitant Traumatic Brain Injury—A Matched Pair Analysis

by Lukas L. Negrin, Robin Ristl, Gregor Wollner and Stefan Hajdu

J. Clin. Med. 2024, 13(14), 4218; https://doi.org/10.3390/jcm13144218 - 19 Jul 2024

Cited by 1 | Viewed by 1124

Abstract

Background/Objectives: Early detection of traumatic brain injury (TBI) is crucial for minimizing secondary neurological damage. Our study aimed to assess the potential of IL-4, IL-6, IL-7, IL-8, IL-10, TNF, and eotaxin serum levels—as a single clinical tool or combined into a panel—for diagnosing TBI in multiple injured patients. Methods: Out of 110 prospectively enrolled polytrauma victims (median age, 39 years; median ISS, 33; 70.9% male) admitted to our level I trauma center over four years, we matched 41 individuals with concomitant TBI (TBI cohort) to 41 individuals without TBI (non-TBI cohort) based on age, gender, Injury Severity Score (ISS), and mortality. Patients’ protein levels were measured upon admission (day 0) and on days 1, 3, 5, 7, and 10 during routine blood withdrawal using one separation gel tube each time. Results: The median serum levels of IL-4, IL-6, IL-7, IL-8, IL-10, and TNF exhibited non-similar time courses in the two cohorts and showed no significant differences on days 0, 1, 3, 5, and 7. However, the median eotaxin levels had similar trend lines in both cohorts, with consistently higher levels in the TBI cohort, reaching significance on days 0, 3, and 5. In both cohorts, the median eotaxin level significantly decreased from day 0 to day 1, then significantly increased until day 10. We also found a significant positive association between day 0 eotaxin serum levels and the presence of TBI, indicating that for every 20 pg/mL increase in eotaxin level, the odds of a prevalent TBI rose by 10.5%. ROC analysis provided a cutoff value of 154 pg/mL for the diagnostic test (sensitivity, 0.707; specificity, 0.683; AUC = 0.718). Conclusions: Our findings identified the brain as a significant source, solely of eotaxin release in humans who have suffered a TBI. Nevertheless, the eotaxin serum level assessed upon admission has limited diagnostic value. IL-4, IL-6, IL-7, IL-8, IL-10, and TNF do not indicate TBI in polytraumatized patients. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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11 pages, 1185 KiB

Open AccessArticle

Settlement Is at the End—Common Trauma Scores Require a Critical Reassessment Due to the Possible Dynamics of Traumatic Brain Injuries in Patients’ Clinical Course

by Jason-Alexander Hörauf, Mathias Woschek, Cora Rebecca Schindler, Rene Danilo Verboket, Thomas Lustenberger, Ingo Marzi and Philipp Störmann

J. Clin. Med. 2024, 13(11), 3333; https://doi.org/10.3390/jcm13113333 - 5 Jun 2024

Cited by 2 | Viewed by 991

Abstract

Background: Scientific studies on severely injured patients commonly utilize the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS) for injury assessment and to characterize trauma cohorts. However, due to potential deterioration (e.g., in the case of an increasing hemorrhage) during the clinical course, the assessment of injury severity in traumatic brain injury (TBI) can be challenging. Therefore, the aim of this study was to investigate whether and to what extent the worsening of TBI affects the AIS and ISS. Methods: We retrospectively evaluated 80 polytrauma patients admitted to the trauma room of our level I trauma center with computed-tomography-confirmed TBI. The initial AIS, ISS, and Trauma and Injury Severity Score (TRISS) values were reevaluated after follow-up imaging. Results: A total of 37.5% of the patients showed a significant increase in AIS_head (3.7 vs. 4.1; p = 0.002) and the ISS (22.9 vs. 26.7, p = 0.0497). These changes resulted in an eight percent reduction in their TRISS-predicted survival probability (74.82% vs. 66.25%, p = 0.1835). Conclusions: The dynamic nature of intracranial hemorrhage complicates accurate injury severity assessment using the AIS and ISS, necessitating consideration in clinical studies and registries to prevent systematic bias in patient selection and subsequent data analysis. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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14 pages, 541 KiB

Open AccessArticle

Athlete Fear Avoidance, Depression, and Anxiety Are Associated with Acute Concussion Symptoms in Athletes

by Ilana Patlan, Gabrielle Gamelin, Kosar Khalaj, Tristan Castonguay and Geoffrey Dover

J. Clin. Med. 2024, 13(8), 2401; https://doi.org/10.3390/jcm13082401 - 20 Apr 2024

Cited by 1 | Viewed by 2452

Abstract

Background: Assessing sport-related concussions in athletes presents challenges due to symptom variability. This study aimed to explore the relationship between acute concussion symptoms and athlete fear avoidance, pain catastrophizing, depression, and anxiety. Anxiety and depression have previously been associated with the number of symptoms after a concussion, but no prior research has examined the possible link between athlete fear avoidance and acute concussion symptoms. Methods: Thirty-four collegiate athletes (mean age = 20.9 ± 1.8 years) were assessed within 48 h of a concussion using the Sport Concussion Assessment Tool 5, Athlete Fear Avoidance Questionnaire (AFAQ), Pain Catastrophizing Scale, and Hospital Anxiety and Depression Scale. Results: Results showed a significant association between the athlete fear avoidance and the number of concussion symptoms (r = 0.493, p = 0.003), as well as depression and anxiety measured by HADS (r = 0.686, p < 0.001). Athlete fear avoidance and HADS scores were predictors of symptom severity, explaining 41% of the variance (p = 0.001). Athletes with higher fear avoidance tended to report more symptoms post concussion. Conclusions: This study underscores the link between athlete fear avoidance, anxiety, depression, and the severity of concussion symptoms. Administering the AFAQ to assess athlete fear avoidance at the initial assessment of a concussion may be helpful in interpreting the symptoms of an acute concussion. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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13 pages, 3340 KiB

Open AccessArticle

Evolution of Severe Closed Head Injury: Assessing Ventricular Volume and Behavioral Measures at 30 and 90 Days Post-Injury

by Serena Campana, Luca Cecchetti, Martina Venturi, Francesco Buemi, Cristina Foti, Antonio Cerasa, Carmelo Mario Vicario, Maria Chiara Carboncini and Francesco Tomaiuolo

J. Clin. Med. 2024, 13(3), 874; https://doi.org/10.3390/jcm13030874 - 2 Feb 2024

Viewed by 1398

Abstract

Background: Assessing functional outcomes in Severe Closed Head Injury (SCHI) is complex due to brain parenchymal changes. This study examines the Ventricles to Intracranial Volume Ratio (VBR) as a metric for these changes and its correlation with behavioral scales. Methods: Thirty-one SCHI patients were included. VBR was derived from CT scans at 3, 30, and 90 days post-injury and compared with Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) assessments at 30 and 90 days. Results: Ten patients were excluded post-decompressive craniectomy or ventriculoperitoneal shunt. Findings indicated a VBR decrease at 3 days, suggesting acute phase compression, followed by an increase from 30 to 90 days, indicative of post-acute brain atrophy. VBR correlated positively with the Marshall score in the initial 72 h, positioning it as an early indicator of subsequent brain atrophy. Nevertheless, in contrast to the Marshall score, VBR had stronger associations with DRS and ERBI at 90 days. Conclusions: VBR, alongside behavioral assessments, presents a robust framework for evaluating SCHI progression. It supports early functional outcome correlations informing therapeutic approaches. VBR’s reliability underscores its utility in neurorehabilitation for ongoing SCHI assessment and aiding clinical decisions. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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13 pages, 234 KiB

Open AccessArticle

Validity of the Norwegian Version of the Needs and Provision Complexity Scale (NPCS) in Patients with Traumatic Brain Injury and Atraumatic Subarachnoid Hemorrhage

by Marit V. Forslund, Ida M. H. Borgen, Tanja Karic, Ingerid Kleffelgård, Solveig L. Hauger, Marianne Løvstad, Marleen R. van Walsem, Emilie I. Howe, Cathrine Brunborg, Nada Andelic and Cecilie Røe

J. Clin. Med. 2024, 13(3), 752; https://doi.org/10.3390/jcm13030752 - 28 Jan 2024

Cited by 2 | Viewed by 1301

Abstract

There is a lack of validated measures in Scandinavian languages to track healthcare service needs and delivery for patients with neurological disabilities. The aim of the present study was to validate the Norwegian version of the clinician and patient Needs and Provision Complexity Scale (NPCS) Needs and Gets. Data on the NPCS from 60 adult patients with traumatic brain injury or atraumatic subarachnoid hemorrhage and symptoms lasting >5 months were assessed for inter-rater/test–retest reliability and agreement, as well as concurrent validity with the Neurological Impairment Scale (NIS), the Functional Independence Measure (FIM), and the Community Integration Questionnaire (CIQ). The clinician NPCS showed good–excellent inter-rater reliability, and the patient NPCS demonstrated good–excellent test–retest reliability. Absolute agreement was moderate–excellent across all clinician and patient items. Concurrent validity was significant, with large correlations between clinician NPCS-Needs and the NIS and FIM total scores, and small–medium correlations between the clinician and patient NPCS-Gets and the NIS and FIM total scores. There were no significant correlations between the NPCS and the CIQ. The study findings support the use of the Norwegian version of the NPCS to assess met and unmet healthcare and support needs for Norwegian-speaking adults with neurological disabilities. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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14 pages, 721 KiB

Open AccessReview

Early Autonomic Dysfunction in Traumatic Brain Injury: An Article Review on the Impact on Multiple Organ Dysfunction

by Pattrapun Wongsripuemtet, Tetsu Ohnuma, Zeljka Minic, Monica S. Vavilala, Joseph B. Miller, Daniel T. Laskowitz, William J. Meurer, Xiao Hu, Frederick K. Korley, Huaxin Sheng and Vijay Krishnamoorthy

J. Clin. Med. 2025, 14(2), 557; https://doi.org/10.3390/jcm14020557 - 16 Jan 2025

Viewed by 1449

Abstract

Background/Objectives: Traumatic brain injury (TBI) is a complex condition and a leading cause of injury-related disability and death, with significant impacts on patient outcomes. Extracranial organ involvement plays a critical role in the outcome of patients following TBI. Method: This review aims to provide a comprehensive overview of the pathophysiology, clinical presentation, and challenges in diagnosing patients with autonomic dysfunction after TBI. The databases used in this review include PubMed/MEDLINE, Cochrane Central Register, and Scopus. Results: Of 172 articles identified for screening, 98 were ultimately included in the review. Conclusion: This review summarized the current evidence on the pathophysiology, clinical presentation, and diagnosis of early autonomic dysfunction. It also emphasizes the effects of autonomic dysfunction on end-organ damage. These insights aim to guide clinicians and researchers toward improving the care for and understanding of autonomic dysfunction in TBI patients, while underscoring the need for further research in this area. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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15 pages, 1019 KiB

Open AccessSystematic Review

Nursing Interventions to Prevent Secondary Injury in Critically Ill Patients with Traumatic Brain Injury: A Scoping Review

by Rita Figueiredo, Cidália Castro and Júlio Belo Fernandes

J. Clin. Med. 2024, 13(8), 2396; https://doi.org/10.3390/jcm13082396 - 19 Apr 2024

Cited by 1 | Viewed by 6767

Abstract

Background: Traumatic brain injury is a prevalent health issue with significant social and economic impacts. Nursing interventions are crucial in preventing secondary injury and improving patient prognosis. This scoping seeks to map and analyze the existing scientific evidence on nursing interventions aimed at preventing secondary injuries in critically ill patients with traumatic brain injury. Methods: The review was conducted according to Arksey and O’Malley’s methodological framework. The electronic databases Pubmed, MEDLINE Complete, CINAHL Complete, Nursing & Allied Health Collection: Comprehensive, Cochrane Central Register of Controlled Trials, and Cochrane Clinical Answers were consulted in May 2023. We included articles published in English and Portuguese between 2010 and 2023. Results: From the initial search, 277 articles were identified, with 15 meeting the inclusion criteria for the review. Nursing interventions for TBI patients include neuromonitoring, therapeutics, analytical surveillance, professional training, and family support. Nurses play a crucial role in detecting neurological changes, administering treatments, monitoring metabolic markers, training staff, and involving families. These interventions aim to prevent secondary injury and improve patient outcomes. Conclusions: By prioritizing evidence-based practice and utilizing innovative technologies, nurses enhance TBI patient care and contribute to overall well-being. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI): Clinical Updates and Perspectives)

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