Traumatic Brain Injury Subtypes Research Articles

Identifying latent subgroups of primary head injury: an explorative latent class analysis on neuropathologically examined medico-legal autopsy cases.

Traumatic brain injury (TBI) is a significant global health concern and frequently encountered in medico-legal autopsies. Previous studies suggest that certain TBI subtypes are more likely to co-occur than others. Therefore, we aimed to explore the potential of latent class analysis (LCA) to identify and characterize primary head injury combinations in neuropathologically examined medico-legal autopsy cases. The dataset comprised 78 cases from the Forensic Medicine Unit of the Finnish Institute for Health and Welfare over the period of 2016-2022. Data on background and circumstantial characteristics as well as primary and secondary head and brain injuries were collected from police documents, medical records, general autopsy reports and neuropathology reports. Latent class solutions with two to five classes were explored to identify clustering of primary head injuries among the sample. The dataset comprised 69.2% males and the median age was 49 years. In LCA, the solutions appeared reasonable, and each class appeared to represent a distinct TBI profile. The two-class solution was found to fit the present dataset best. Class 1 was characterized by older age, presence of an underlying CNS disease, and less diverse primary head injuries; these were interpreted as suggestive of lower traumatic forces. Class 2 was characterized by male sex and assaults as a prominent injury circumstance; subarachnoid and intracerebral/ventricular haemorrhages and contusions were classified exclusively into this class. In conclusion, this study identified two distinct subgroups of primary head injuries. Understanding typical injury combinations related to distinct circumstances could assist not only forensic pathologists but also clinicians treating TBI patients. However, the present latent class solution should not be interpreted as "ground truth", but instead further research is needed.

Development of Seizures Following Traumatic Brain Injury: A Retrospective Study.

Objectives: The multifaceted impact of Traumatic brain injury (TBI) encompasses complex healthcare costs and diverse health complications, including the emergence of Post-Traumatic Seizures (PTS). In this study, our goal was to discern and elucidate the incidence and risk factors implicated in the pathogenesis of PTS. We hypothesize that the development of PTS following TBI varies based on the type and severity of TBI. Methods: Our study leveraged the Nationwide Inpatient Sample (NIS) to review primary TBI cases spanning 2016-2020 in the United States. Admissions featuring the concurrent development of seizures during the admission were queried. The demographic variables, concomitant diagnoses, TBI subtypes, hospital charges, hospital length of stay (LOS), and mortality were analyzed. Results: The aggregate profile of TBI patients delineated a mean age of 61.75 (±23.8) years, a male preponderance (60%), and a predominantly White demographic (71%). Intriguingly, patients who encountered PTS showcased extended LOS (7.5 ± 9.99 vs. 6.87 ± 10.98 days, p < 0.001). Paradoxically, PTS exhibited a reduced overall in-hospital mortality (6% vs. 8.1%, p < 0.001). Notably, among various TBI subtypes, traumatic subdural hematoma (SDH) emerged as a predictive factor for heightened seizure development (OR 1.38 [1.32-1.43], p < 0.001). Conclusions: This rigorous investigation employing an extensive national database unveils a 4.95% incidence of PTS, with SDH accentuating odds of seizure risk by OR: 1.38 ([1.32-1.43], p < 0.001). The paradoxical correlation between lower mortality and PTS is expected to be multifactorial and necessitates further exploration. Early seizure prophylaxis, prompt monitoring, and equitable healthcare provision remain pivotal avenues for curbing seizure incidence and comprehending intricate mortality trends.

Mass Spectrometry-Based Approaches for Clinical Biomarker Discovery in Traumatic Brain Injury.

Precision treatments to address the multifaceted pathophysiology of traumatic brain injury (TBI) are desperately needed, which has led to the intense study of fluid-based protein biomarkers in TBI. Mass Spectrometry (MS) is increasingly being applied to biomarker discovery and quantification in neurological disease to explore the proteome, allowing for more flexibility in biomarker discovery than commonly encountered antibody-based assays. In this narrative review, we will provide specific examples of how MS technology has advanced translational research in traumatic brain injury (TBI) focusing on clinical studies, and looking ahead to promising emerging applications of MS to the field of Neurocritical Care. Proteomic biomarker discovery using MS technology in human subjects has included the full range of injury severity in TBI, though critically ill patients can offer more options to biofluids given the need for invasive monitoring. Blood, urine, cerebrospinal fluid, brain specimens, and cerebral extracellular fluid have all been sources for analysis. Emerging evidence suggests there are distinct proteomic profiles in radiographic TBI subtypes, and that biomarkers may be used to distinguish patients sustaining TBI from healthy controls. Metabolomics may offer a window into the perturbations of ongoing cerebral insults in critically ill patients after severe TBI. Emerging MS technologies may offer biomarker discovery and validation opportunities not afforded by conventional means due to its ability to handle the complexities associated with the proteome. While MS techniques are relatively early in development in the neurosciences space, the potential applications to TBI and neurocritical care are likely to accelerate in the coming decade.

Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue

The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.

Subdural hematoma as a major determinant of short-term outcomes in traumatic brain injury.

OBJECTIVE Early radiographic findings in patients with traumatic brain injury (TBI) have been studied in hopes of better predicting injury severity and outcome. However, prior attempts have generally not considered the various types of intracranial hemorrhage in isolation and have typically not excluded patients with potentially confounding extracranial injuries. Therefore, the authors examined the associations of various radiographic findings with short-term outcome to assess the potential utility of these findings in future prognostic models. METHODS The authors retrospectively identified 1716 patients who had experienced TBI without major extracranial injuries, and categorized them into the following TBI subtypes: subdural hematoma (SDH), traumatic subarachnoid hemorrhage, intraparenchymal hemorrhage (which included intraventricular hemorrhage), and epidural hematoma. They specifically considered isolated forms of hemorrhage, in which only 1 subtype was present. RESULTS In general, the presence of an isolated SDH was more likely to result in worse outcomes than the presence of other isolated forms of traumatic intracranial hemorrhage. Discharge to home was less likely and perihospital mortality rates were generally higher in patients with SDH. These findings were not simply related to age and were not fully captured by the admission Glasgow Coma Scale (GCS) score. The presence of SDH had a much higher sensitivity for poor outcome than the presence of other TBI subtypes, and was more sensitive for these poor outcomes than having a low GCS score (3-8). CONCLUSIONS In these ways, SDH was the most important finding associated with poor outcome, and the authors show that consideration of SDH, specifically, can augment age and GCS score in classification and prognostic models for TBI.

Predicting progressive hemorrhagic injury from isolated traumatic brain injury and coagulation

Progressive hemorrhagic injury (PHI) in traumatic brain injury (TBI) patients is associated with poor outcomes. Early prediction of PHI is difficult yet vital. We hypothesize that TBI subtype and coagulation would be predictors of PHI. This was a retrospective analysis of highest level activation adult trauma patients with evidence of TBI (head Abbreviated Injury Scale ≥3). Coagulopathy was determined using rapid thrombelastography (r-TEG), complete blood counts, and conventional coagulation tests obtained on arrival. Patients were dichotomized into PHI and stable groups based on head computerized CT. Subtypes of TBI included subdural hematoma, intraparenchymal contusions (IPC), subarachnoid hemorrhage, epidural hematoma, and combined. Data are reported as median values with interquartile range (IQR). Multivariate logistic regression was used to assess the effect of subtype and coagulation on PHI. We included 279 isolated TBI patients who met study criteria. There were 157 patients (56%) who experienced PHI; 122 (44%) were stable on repeat CT. Patients with PHI were older, had fewer hospital-free days, and higher mortality (all P<.001). No differences were noted in r-TEG parameters between groups; however, coagulopathy and age were independent predictors of progression in all subtypes (odds ratio [OR], 1.81; 95% CI, 1.09-3.01 [P=.021]; OR, 1.02, 95% CI, 1.01-1.04 [P=.006]). Controlling for age, Glasgow Coma Scale score, and coagulopathy, patients with IPC were more likely to experience PHI (OR, 4.49; 95% CI, 2.24-8.98; P<.0001). This study demonstrates that older patients with coagulation abnormalities and IPC on admission are more likely to experience PHI, identifying a target population for earlier therapies.

Effect of hypothalamic- pituitary- adrenal axis on prognosis of patients with traumatic brain injury

Objective To observe the influence of hypothalamic- pituitary- adrenal(HPA) axis on the prognosis of patients with traumatic brain injury(TBI). Methods 140 cases of TBI were fallen into the following groups:mild group(26 cases), moderate group(34 cases),severe group(64 cases), and ultra severe group(16 cases).The serum cortisol was measured at 8∶00 am on the 3rd day after TBI.The dexamethasone suppression test was done to assay the stress response ability of HPA which might be injured in TBI.0.75 mg dexamethasone was taken orally or through a stomach tube at 00∶00 am of the 4th day post- TBI, and then the serum cortisol was assayed at 8∶00 am on the 4th day post-TBI.The rate of the pulmonary infection, average hospitalization days and Glasgow Outcome Scale (GOS) were recorded. Results The rate of HPA axis dysfunction was 11.6%, 35.3%, 64.1% and 81.3% in the mild group, moderate group, severe group and ultra severe group, respectively.The difference among the four subtypes of TBI was statistically significant(χ2trend= 27.432,P< 0.01). The rate of the pulmonary infection,average hospitalization days and GOS were respectively counted in different subtypes of TBI between the patients with normal and impaired HPA.The differences in the above items were significant(P< 0.05)between the same subtypes of TBI with or without HPA axis dysfunction. Conclusion HPA axis function relates to the prognosis of TBI patients. Key words: Hypothalamic-pituitary-adrenal axis; Traumatic brain injury; Prognosis

Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?

The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes. 107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to "diffuse" (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or "focal" (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 × 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP. Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx >0.1), CPP >70 mmHg was associated with better outcome (p = 0.03). TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.

Functional Assessment of Long-Term Deficits in Rodent models of Traumatic Brain Injury

Traumatic brain injury (TBI) ranks as the leading cause of mortality and disability in the young population worldwide. The annual US incidence of TBI in the general population is estimated at 1.7 million per year, with an estimated financial burden in excess of US$75 billion a year in the USA alone. Despite the prevalence and cost of TBI to individuals and society, no treatments have passed clinical trial to clinical implementation. The rapid expansion of stem cell research and technology offers an alternative to traditional pharmacological approaches targeting acute neuroprotection. However, preclinical testing of these approaches depends on the selection and characterization of appropriate animal models. In this article we consider the underlying pathophysiology for the focal and diffuse TBI subtypes, discuss the existing preclinical TBI models and functional outcome tasks used for assessment of injury and recovery, identify criteria particular to preclinical animal models of TBI in which stem cell therapies can be tested for safety and efficacy, and review these criteria in the context of the existing TBI literature. We suggest that 2 months post-TBI is the minimum period needed to evaluate human cell transplant efficacy and safety. Comprehensive review of the published TBI literature revealed that only 32% of rodent TBI papers evaluated functional outcome ≥1 month post-TBI, and only 10% evaluated functional outcomes ≥2 months post-TBI. Not all published papers that evaluated functional deficits at a minimum of 2 months post-TBI reported deficits; hence, only 8.6% of overall TBI papers captured in this review demonstrated functional deficits at 2 months or more postinjury. A 2-month survival and assessment period would allow sufficient time for differentiation and integration of human neural stem cells with the host. Critically, while trophic effects might be observed at earlier time points, it will also be important to demonstrate the sustainability of such an effect, supporting the importance of an extended period of in vivo observation. Furthermore, regulatory bodies will likely require at least 6 months survival post-transplantation for assessment of toxicology/safety, particularly in the context of assessing cell abnormalities.