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Traumatic Brain Injury: Current Treatment and Future Options

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

Deadline for manuscript submissions: closed (20 January 2026) | Viewed by 18899

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Dr. Ismail Zaed

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Department of Neurosurgery, Neurocenter of the Southern Switzerland, Ente Ospedaliero Cantonale, CH-2900 Lugano, Switzerland
Interests: neurosurgical anatomy; skull base surgery; endoscopic surgery; neuro-oncological surgery; neurovascular surgery; spine surgery; machine learning; enhanced recovery after surgery; global neurosurgery
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Dear Colleagues,

Traumatic brain injury (TBI) presents a significant global health challenge; however, its critical aspects, such as a reliable pathophysiological classification and targeted treatments, still lack sufficient data. While there has been a surge in TBI-related publications, the translation of these research findings into clinical practice remains frustratingly slow.

Encouragingly, substantial international efforts offer hope for significant advancements in TBI diagnostics and patient care. Given its interdisciplinary nature, TBI spans multiple medical specialties, ranging from emergency medicine and intensive care to rehabilitation and psychiatry. Consequently, reports on scientific progress in this field are dispersed across various journals, each with its own narrow focus, complicating efforts to grasp the full scope of TBI medicine and emerging trends.

The rapid evolution of technical solutions in laboratory medicine, imaging, and neurophysiology has yielded new tools with numerous potential clinical applications. Few medical domains demand personalized medicine and the integration of artificial intelligence more than TBI, given its complexity as an individual disease. Despite the proliferation of innovative technologies and their potential applications, everyday TBI care has seen minimal progress over the past two decades and still heavily relies on the subjective experience and judgment of treating clinicians.

This Special Issue aims to provide an up-to-date review of TBI for all the healthcare professionals who meet and treat TBI patients at various levels and across different facilities. The focus of this Special Issue is on clinically relevant recent developments and emerging trends, with the aim of providing the reader with a good understanding of the current state of TBI medicine.

Dr. Ismail Zaed
Guest Editor

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Keywords

traumatic brain injury
trauma
biomarkers
post-traumatic outcome
epidemiology

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Published Papers (8 papers)

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Research

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9 pages, 223 KB

Open AccessArticle

Predictive Factors in Development of Postoperative Delirium in Chronic Subdural Hematomas: A Prospective Multicenter Study

by Ismail Zaed, Salvatore Chibbaro, Francesco Marchi, Luca Ricciardi, Leonardo Di Cosmo, Charles Henry Mallereau, Guillaume Dannhoff, Julien Todeschi, Mario Ganau, Davide Milani and Andrea Cardia

J. Clin. Med. 2026, 15(9), 3412; https://doi.org/10.3390/jcm15093412 - 29 Apr 2026

Viewed by 334

Abstract

Introduction: Chronic subdural hematoma (CSDH) is a complex disease with an overall incidence of 1.7–20.6 per 100,000 persons per year and is more commonly encountered in the elderly population. It is projected to be one of the most common neurosurgical procedures. Postoperative delirium is a common complication associated with the elderly, causing increased morbidity and prolonged hospital stay. However, its risk factors in chronic subdural hematoma patients have not been well studied. Methods: A total of 202 consecutive patients with chronic subdural hematoma at different neurosurgical centers in Europe between January 2023 and June 2025 were enrolled. Various clinical indicators were analyzed to identify independent risk factors for postoperative delirium using univariate and multivariate regression analyses. Results: Out of the 202 patients (age, 71 (IQR, 18); female-to-male ratio, 1:2.7) studied, 63 (31.2%) experienced postoperative delirium. Univariate analysis identified age (p < 0.001), gender (p = 0.014), restraint belt use (p < 0.001), electrolyte imbalance (p < 0.001), visual analog scale (VAS) pain score (p < 0.001), hematoma thickness (p < 0.001), midline shift (p < 0.001), hematoma side (p = 0.013), hematoma location (p = 0.018), and urinal catheterization (p = 0.028) as significant factors. Multivariate regression analysis confirmed the significance of restraint belt use (B = 7.657, p < 0.001), electrolyte imbalance (B = −3.993, p = 0.001), VAS pain score (B = 2.331, p = 0.016), and midline shift (B = 0.335, p = 0.007). Hematoma thickness and age had no significant impact. Conclusions: Increased midline shift and VAS pain scores, alongside restraint belt use and electrolyte imbalance, elevate delirium risk in chronic subdural hematoma surgery. Our prediction models may offer a reference value in this context. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

12 pages, 423 KB

Open AccessArticle

Relative Incidence of New-Onset Substance Use Disorders Following Traumatic Brain Injury: A Global Retrospective Multicenter Analysis Using the TriNetX Database

by Zachary T. Hoglund, Christopher Sollenberger, Kyle W. Scott, John D. Arena, Visish M. Srinivasan, Jan-Karl Burkhardt, Jeffrey Turnbull, Julio Rosado-Philippi, Heather Heitkotter, Alexander I. Helfand, Daniel W. Griepp and Chad F. Claus

J. Clin. Med. 2026, 15(3), 1182; https://doi.org/10.3390/jcm15031182 - 3 Feb 2026

Viewed by 882

Abstract

Background: Traumatic brain injury (TBI) imposes a substantial public health burden through long-term physical, cognitive, and psychiatric effects. This includes substance use disorders (SUDs) for which TBI is a demonstrated risk factor; however, prior studies have not comprehensively compared relative incidences of SUD subtypes post-TBI or differences between intracranial hemorrhage (ICH) and non-ICH TBI in patients without prior SUD history. This global retrospective analysis using the TriNetX database aims to quantify new-onset SUD incidence post-TBI in the largest cohort of patients evaluated to date, with cohorts stratified by SUD subtype and ICH versus non-ICH TBI, to highlight opportunities for post-injury care models to mitigate SUD risk. Methods: De-identified data from the TriNetX Research Network were used to select patients with TBI (n = 1,889,112) and define distinct cohorts based upon the presence (n = 420,868) or absence (n = 1,471,592) of ICH. Patients with previously diagnosed SUD before the date of TBI were excluded. Patient demographics and medical comorbidities were calculated for each group. The incidence of new SUD diagnosis over the lifetime and at 1-, 3-, and 5-years post-TBI were calculated and compared. Subtypes of SUD were defined and calculated based on the specific substance used. Propensity scores were calculated to create balanced matched ICH and non-ICH cohorts (n = 331,812 each) were used for comparisons of 5-year SUD incidence. Results: In the full TBI cohort, 5-year new SUD incidence was 4.2% overall, with nicotine (2.4%) and alcohol (1.1%) predominating, followed by cannabis (0.9%) and opioids (0.4%). Rates of SUDs increased over time, but attenuated beyond 5 years, with approximately 50% of those who would ultimately be diagnosed with SUD manifesting (lifetime) by 3 years post-TBI. After propensity matching, non-ICH TBI showed higher 5-year risk for any SUD (4.2% vs. 3.6%; risk difference −0.65%, p < 0.0001) and all subtypes (p < 0.05) except inhalants (p = 0.53). Conclusions: This largest-to-date analysis of new-onset SUD post-TBI demonstrates significantly higher rates of SUD in TBI patients; rates of nicotine, alcohol, cannabis, and opioid use disorders were most common. Non-ICH TBI patients demonstrated greater rates of SUD after injury than patients with ICH-associated TBI. Of patients suffering from TBI without ICH who would eventually be diagnosed with SUD, approximately 50% had obtained that diagnosis within 3 years of the injury. Taken together, these findings demonstrate the clinical need for routine SUD screening in post-TBI care, especially for 3 years post-injury. Such an intervention has the potential to significantly alleviate the public health burden and associated cost of care for TBI-associated substance use disorder patients. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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17 pages, 734 KB

Open AccessArticle

Predictive Accuracy of Glasgow Coma Scale and Pupillary Data on Presence of Traumatic Brain Injury

by Diana Schüller, Arasch Wafaisade, Rolf Lefering, Filippo Migliorini, Eftychios Bolierakis, Matthias Weuster, Yusuke Kubo, Matthias Fröhlich and Arne Driessen

J. Clin. Med. 2026, 15(2), 697; https://doi.org/10.3390/jcm15020697 - 15 Jan 2026

Viewed by 906

Abstract

Background/Objectives: The GCS is widely used to assess a patient’s level of consciousness after trauma. Although not a diagnostic tool for traumatic brain injury (TBI), prehospital clinicians frequently rely on GCS findings—along with pupil exam, mechanism of injury, and clinical presentation, to estimate the likelihood that TBI may be present before imaging is available. However, the GCS has known limitations and fails to identify a significant proportion of TBI patients. This study aimed to evaluate the association between GCS scores and the presence of TBI, and whether additional clinical variables improve its discriminatory value. Methods: This retrospective cohort study analyzed data from trauma patients registered in the TraumaRegister DGU^® between 2015 and 2017. TBI was defined as a head injury with an Abbreviated Injury Scale (AISHead) score of ≥2. Inclusion criteria consisted of trauma team activations with a maximum AIS ≥ 3 and/or the need for intensive care. Prognostic values were assessed using multivariable logistic regression analysis. Results: 40,216 patients were included of which 17,205 (42.8%) were diagnosed with TBI and 23,011 (57.2%) were non-TBI patients. In the TBI group, 36.4% (n = 6216) presented with an initial GCS of 15 prehospitally. 17.8% (n = 3059) of TBI patients had anisocoric or bilaterally dilated pupils, 22.1% (n = 3799) had sluggish or fixed light reactivity and 17% (n = 2934) had no motoric response in Eppendorf-Cologne Scale (ECS) motor component. GCS score by itself showed better TBI prediction value than pupil size or reactivity or motor component alone. Nevertheless, substantial misclassification was observed when using GCS alone: 25.7% of patients with a normal GCS (15) had TBI (AIS Head ≥ 2), while 19.1% of patients with GCS 3 had no TBI. In the non-TBI group, 2.7% (n = 622) had a GCS of 3, 2.9% (n = 685) had anisocoric or bilaterally dilated pupils, 4.2% (n = 960) had sluggish or fixed light reactivity and 3.3% (n = 751) had no motoric response. Even at the lowest GCS score of 3, 19.1% of patients did not have TBI, while a normal GCS of 15 still included 25.7% of patients with TBI. Conclusions: The expanded model combining GCS with pupillary assessment and the ECS motor component demonstrated superior performance in prehospital TBI detection compared with the GCS alone. Implementing an extended GCS incorporating pupillary and ECS assessment may facilitate earlier recognition of TBI and support timely triage decisions; however, potential effects on patient outcomes require confirmation in prospective studies. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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14 pages, 682 KB

Open AccessArticle

Evaluation of Traumatic Brain Injury Severity Using the Abbreviated Injury Scale and the Injury Severity Score: A Retrospective Study in Two Eastern European Centers

by Iulia-Maria Vadan, Diana Grad, Stefan Strilciuc, Alina Vasilica Blesneag, Marcin Michalak, Vitalie Vacaras, Adina Stan and Dafin F. Muresanu

J. Clin. Med. 2025, 14(17), 6259; https://doi.org/10.3390/jcm14176259 - 4 Sep 2025

Cited by 2 | Viewed by 1569

Abstract

Introduction: Traumatic brain injury (TBI) is a significant global public health issue, with long-term impacts on patients. This study examines the relationship between TBI severity, as measured by the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS) at admission, and various sociodemographic, clinical, and injury-related factors. Methods: We conducted a retrospective analysis using data from 164 adult TBI patients. All were admitted between March 2020 and June 2023 to two Eastern European tertiary hospitals. Variables included sex, age, education, employment, marital status, injury type and cause, place of injury, and clinical measures such as the Marshall score, AIS, and ISS. Statistical methods included Pearson’s Chi-squared, Fisher’s exact, Spearman correlation, Wilcoxon, and Kruskal–Wallis tests. Results: Most patients were male (65.9%), retired (59.8%), and urban residents (73.8%), with a mean age of 64.98 years. The most frequent mechanism of injury was falls (76.2%), typically occurring at home (61%). The predominant injury type was closed head trauma (93.3%). Most patients had mild AIS scores (75%), and the mean ISS was 6.52 (SD: 4.55). Statistically significant group differences were found for AIS among categories of Modified Marshall Score, injury type, and education categories and for ISS among categories of the Modified Marshall Score, injury type, cause and place of injury, employment status, and sex. No significant correlations were found between AIS or ISS and age or hospital length of stay. Conclusions: AIS is more anatomically focused. ISS reflects broader systemic injury patterns and is more influenced by contextual factors. These findings are particularly relevant for the Eastern European population and can help develop better healthcare policies for the region. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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13 pages, 385 KB

Open AccessArticle

Glasgow Coma Scale Score at Admission in Traumatic Brain Injury Patients: A Multicenter Observational Analysis

by Iulia-Maria Vadan, Diana Grad, Stefan Strilciuc, Emanuel Stefanescu, Olivia Verisezan Rosu, Marcin Michalak, Alina Vasilica Blesneag and Dafin Muresanu

J. Clin. Med. 2025, 14(15), 5195; https://doi.org/10.3390/jcm14155195 - 22 Jul 2025

Cited by 4 | Viewed by 4433

Abstract

Introduction: Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, with the Glasgow Coma Scale (GCS) serving as a tool to measure injury severity. This study aimed to investigate the relationship between GCS admission scores and various socio-demographic, clinical, injury-related, and hospital-related variables in patients with TBI across two tertiary care centers in Eastern Europe, a region that remains underrepresented in the literature. Methods: A retrospective observational study was conducted using data from 119 TBI patients admitted between March 2020 and June 2023 at Cluj County Emergency Hospital (Romania) and Saint Vincent Hospital (Poland). GCS scores were analyzed as both categorical and continuous variables. Statistical analyses included Wilcoxon and Kruskal–Wallis tests for group comparisons and Spearman correlations for continuous variables. Results: Most patients included suffered a mild TBI (GCS score between 13 and 15). There were significant associations between GCS scores and post-traumatic amnesia (p < 0.05), discharge status (p < 0.01), discharge destination (p < 0.01), and education level (p < 0.01). GCS scores at admission were linked to survival, absence of post-traumatic amnesia, higher education levels, and home discharge. No significant differences observed across sex, residence, employment status, injury type, cause, or mechanism of injury. A weak but significant negative correlation was observed between GCS and length of hospital stay (rho = −0.229, p > 0.05), while age showed a non-significant correlation. Conclusions: The GCS score at admission is significantly associated with various clinical and socio-demographic outcomes in TBI patients, supporting the utility of the GCS score as a prognostic tool. The predominance of mild cases and the absence of radiological data, such as cerebral contusions or epidural or subdural hematomas, limit the generalizability of the findings. Further studies with larger samples and comprehensive imaging data are necessary to validate these findings. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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14 pages, 827 KB

Open AccessArticle

Clinical, Neuroimaging, and Genetic Markers Associated with Cognitive and Functional Outcomes After Traumatic Brain Injury

by Khrystyna Duve, Svitlana Shkrobot, Pavlo Petakh, Valentyn Oksenych and Oleksandr Kamyshnyi

J. Clin. Med. 2025, 14(8), 2796; https://doi.org/10.3390/jcm14082796 - 18 Apr 2025

Viewed by 1337

Abstract

Background: Traumatic brain injury (TBI) is a major cause of long-term disability worldwide, often leading to progressive cognitive and functional impairments. This study aimed to investigate the underlying factors contributing to long-term deterioration in TBI patients. Methods: We conducted a comprehensive evaluation of 145 patients aged 18–66 years with a documented history of TBI and ongoing cognitive and behavioral deficits. Assessments included neuroimaging, laboratory tests, genetic analysis, and standardized tools such as the Montreal Cognitive Assessment (MoCA) and the Barthel Index. Results: Structural brain abnormalities, including ventricular enlargement and gliosis, were observed in a substantial portion of the cohort. Persistent neuroinflammatory markers were also identified. Genetic analysis revealed a significant association between cognitive decline and polymorphisms in the ACE and PON1 genes. Patients carrying these variants were more likely to exhibit reduced cognitive performance and greater functional limitations. Conclusion: These findings suggest that genetic predisposition, chronic neuroinflammation, and structural brain damage collectively contribute to long-term outcomes following TBI. This highlights the potential of genetic and imaging biomarkers in identifying high-risk individuals and supports the need for personalized approaches to diagnosis, monitoring, and treatment in chronic TBI management. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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23 pages, 1203 KB

Open AccessArticle

Balance Performance After Mild Traumatic Brain Injury in Children and Adolescents: Instrumented BESS in the Acute Situation and Over Time

by Nils K. T. Schönberg, Johanna Wagner, Korbinian Heinrich, Ida Kandler, Tobias Graf, Rieke Böddeker, Lea Zinke, Nicole Fabri, Julia Wilke, Florian Hoffmann, A. Sebastian Schröder, Anne-Sophie Holler, Alexandra Fröba-Pohl, Oliver Muensterer, Doreen Huppert, Matthias Hösl, Florian Heinen and Michaela V. Bonfert

J. Clin. Med. 2025, 14(5), 1666; https://doi.org/10.3390/jcm14051666 - 28 Feb 2025

Viewed by 1898

Abstract

Background: Mild traumatic brain injury (mTBI) in the pediatric population is a significant public health concern, often associated with persistent post-concussion symptoms, including postural instability. Current tools for assessing postural control, such as the Balance Error Scoring System (BESS), lack integration with objective metrics. Incorporating force plate sensors into BESS assessments may enhance diagnostic accuracy and support return-to-play or sports decisions. This study evaluates postural performance in children with mTBI compared to controls using an instrumented BESS and examines recovery trajectories after mTBI. Methods: This prospective, longitudinal study included 31 children with mTBI (12.01 ± 3.28 years, 20 females) and 31 controls (12.31 ± 3.27 years, 18 females). Postural control was assessed using an instrumented BESS protocol during standing on a ground reaction force plate at three timepoints: within 72 h post injury (T1), at two weeks (T2), and three months after trauma (T3). Posturographic parameters derived from the displacement of the center of pressure included the ellipse area, path length, and mean velocity in the anterior–posterior and medio–lateral directions. Symptom burden was monitored using the Post-Concussion Symptom Inventory (PCSI). Results: The BESS total scores did not differ significantly between the groups at any timepoint. A significant reduction in BESS errors over time was observed exclusively in the two-legged stance on a soft surface (p = 0.047). The instrumented BESS revealed higher body swaying in the mTBI group compared to controls, particularly under demanding conditions. Significant between-group differences were most frequently observed in single-leg soft surface (38% of comparisons) and two-legged soft surface stances (29%). In those cases, path length and mean velocity differed between groups, respectively. Ellipse area did not show significant differences across conditions. Conclusions: An instrumented BESS has the potential to enhance the detection of subtle postural deficits in pediatric mTBI patients. Specifically, more demanding conditions with altered sensory-proprioceptive input and path length as an outcome measure should be focused on. This study underscores the need for tailored and age-appropriate objective and quantitative balance assessments to improve diagnostic precision in pediatric mTBI populations. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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13 pages, 1051 KB

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The Brain Fatigue Syndrome—Symptoms, Probable Definition, and Pathophysiological Mechanisms

by Birgitta Johansson and Lars Rönnbäck

J. Clin. Med. 2025, 14(10), 3271; https://doi.org/10.3390/jcm14103271 - 8 May 2025

Cited by 2 | Viewed by 6371

Abstract

Fatigue is a common consequence of traumatic brain injury, neurological diseases or developmental disorders, and systemic inflammatory diseases, including autoimmune conditions that affect the brain. This condition is characterized by reduced endurance for cognitive tasks, diminished quality of life, and impaired work capacity. In addition to cognitive difficulties, individuals often experience disproportionately long recovery times after demanding tasks, emotional instability, stress sensitivity, sensory sensitivity, impaired ability to initiate activities, and sleep disturbances. Tension headaches frequently occur when the brain is excessively activated by mental activity. In this paper, we propose the term “Brain Fatigue Syndrome” (BFS) as a collective name for the symptoms closely associated with this pathological fatigue resulting from brain impact. BFS can be identified through interviews and measured using the self-assessment instrument, the Mental Fatigue Scale (MFS). We suggest potential underlying mechanisms at the cellular level for the BFS symptom complex, including astrocyte dysfunction with impaired glutamate signaling and glucose uptake, mitochondrial dysfunction, blood–brain barrier dysfunction, and the activation of microglia and mast cells. In conclusion, BFS suggests a general brain impact. The symptoms associated with BFS typically resolve when the injury or disease heals. However, in some individuals, BFS persists even after the injury or illness has ostensibly healed. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Current Treatment and Future Options)

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