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Background: Diffuse axonal injury (DAI), a feature seen in severe traumatic brain injury (TBI), is associated with substantial morbidity and mortality. Although blood pressure variability (BPV) has been shown to impact TBI outcomes overall, its relevance in DAI cases remains uncertain. We investigated whether 24-hour post-injury BPV and other clinical factors were linked to patient outcomes.Methods: We conducted a retrospective analysis of Level I trauma center-admitted TBI patients with radiographic DAI diagnosis (computed tomography/magnetic resonance imaging). Hospital disposition (home, nursing facility, hospice/death) and Glasgow Coma Scale (GCS) on hospital day 5 (HD5GCS) were outcomes of interest. We assessed associations with clinical factors using ordinal logistic regression.Results: Among 153 patients (mean age 49 ± 20 years, 74% male), median admission GCS was 5.0 (3.0-12.5), HD5GCS was 8.0 (6.0-11), and median hospital stay was 25 (15.5-34.5) days. The BPV, measured as successive variation in systolic blood pressure (SBPSV) and standard deviation in systolic blood pressure (SBPSD), was not significantly associated with hospital disposition. SBPSV and SBPSD were also not associated with our secondary outcome of HD5GCS. Initial international normalized ratio (INR) (Coefficient -3.67, odds ratio [OR] 0.03, 95% confidence interval [CI] 0.00-0.70), cerebral contusion (Coeff -2.39, OR 0.09, 95% CI 0.01-0.75), and HD5GCS (Coeff 0.59, OR 1.80, 95% CI 1.30-2.49) were associated with increased odds of discharge to hospice or death. Administration of blood products (Coeff 1.06, OR 2.89, 95% CI 1.10-7.60), vasopressors (Coeff 1.40, OR 4.05, 95% CI 1.37-11.96), and hyperosmolar therapy (Coeff 1.23, OR 3.41, 95% CI 1.36-8.54), and concurrent intraventricular hemorrhage (Coeff 0.99, OR 2.70, 95% CI 0.86-6.49) were linked to poorer HD5GCS.Conclusion: Blood pressure variability was not correlated with outcomes in patients with diffuse axonal injury. Low Glasgow Coma Score on hospital day 5, high initial INR, and concomitant cerebral contusion were associated with poorer outcomes.

Traumatic brain injury (TBI) results from physical or traumatic injuries to the brain's surrounding bony structures and associated tissues, which can lead to various sequelae, including simple concussion, acute epidural hematoma, parenchymal contusions, subarachnoid hemorrhage, diffuse axonal injury, and chronic traumatic encephalopathy. Susceptibility-weighted imaging (SWI) has enhanced the accuracy of neuroimaging for these injuries. SWI is based on 3D gradient echo magnetic resonance imaging (MRI) with long echo times and flow compensation. Owing to its sensitivity to deoxyhemoglobin, hemosiderin, iron, and calcium, SWI is extremely informative and superior to conventional MRI for the diagnosis and follow-up of patients with acute, subacute, and prolonged hemorrhage. This systematic review aimed to evaluate and summarize the published articles that report SWI results for the evaluation of TBI and to determine correlations between clinical status and SWI results. Consequently, our analysis also aimed to identify the appropriate MRI sequences to use in the assessment of patients with TBI. We searched the Medline and Embase online electronic databases for relevant papers published from 2012 onwards. We found that SWI had higher sensitivity than gradient echo MRI in detecting and characterizing microbleeds in TBIs and was able to differentiate diamagnetic calcifications from paramagnetic microhemorrhages. However, it is important that future research not only continues to evaluate the utility of SWI in TBIs but also attempts to overcome the limitations of the studies described in this review, which should help validate the conclusions and recommendations from our analysis. [ABSTRACT FROM AUTHOR]

Severe intracranial trauma during torture or assault is reportedly caused by shaken adult syndrome. However, intracranial traumas caused by natural forces, excluding human factors and collision impact, are extremely rare. We report an autopsy case of shaken adult syndrome caused by ocean wave forces. A man in his 40s without any medical history was washed away by a wave during recreational fishing. He was found approximately 500 m away from the fishing point drifting on the ocean in a state of cardiopulmonary arrest and was confirmed dead, with no response to cardiopulmonary resuscitation, 3 h after the accident. The autopsy revealed no mechanical trauma to the entire body surface, including the head. Both lungs were inflated, and pleural effusion was observed. The brain was swollen and congested, and subarachnoid hemorrhage was observed in the interhemispheric fissure and the convexity of the parietal occipital lobe. Macroscopic and microscopic hemorrhage spots were found in the brain, and the results of the blood alcohol test and urinary toxicological screening were negative. The cause of death was determined as drowning. This case demonstrates a rare but notable mechanism of injury observed in immersed bodies. [ABSTRACT FROM AUTHOR]

Objective: Application of Tandem Mass Tags (TMT)-based LC–MS/MS analysis to screen for differentially expressed proteins (DEPs) in traumatic axonal injury (TAI) of the brainstem and to predict potential biomarkers and key molecular mechanisms of brainstem TAI. Methods: A modified impact acceleration injury model was used to establish a brainstem TAI model in Sprague–Dawley rats, and the model was evaluated in terms of both functional changes (vital sign measurements) andstructural changes (HE staining, silver-plating staining and β-APP immunohistochemical staining). TMT combined with LC–MS/MS was used to analyse the DEPs in brainstem tissues from TAI and Sham groups. The biological functions of DEPs and potential molecular mechanisms in the hyperacute phase of TAI were analysed by bioinformatics techniques, and candidate biomarkers were validated using western blotting and immunohistochemistry on brainstem tissues from animal models and humans. Results: Based on the successful establishment of the brainstem TAI model in rats, TMT-based proteomics identified 65 DEPs, and bioinformatics analysis indicated that the hyperacute phase of TAI involves multiple stages of biological processes including inflammation, oxidative stress, energy metabolism, neuronal excitotoxicity and apoptosis. Three DEPs, CBR1, EPHX2 and CYP2U1, were selected as candidate biomarkers and all three proteins were found to be significantly expressed in brainstem tissue 30 min-7 days after TAI in both animal models and humans. Conclusion: Using TMT combined with LC–MS/MS analysis for proteomic study of early TAI in rat brainstem, we report for the first time that CBR1, EPHX2 and CYP2U1 can be used as biomarkers of early TAI in brainstem by means of western blotting and immunohistochemical staining, compensating for the limitations of silver-plating staining and β-APP immunohistochemical staining, especially in the case of very short survival time after TAI (shorter than 30 min). A number of other proteins that also have a potential marker role are also presented, providing new insights into the molecular mechanisms, therapeutic targets and forensic identification of early TAI in brainstem. [ABSTRACT FROM AUTHOR]

BackgroundTraumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied.MethodsPatients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups.ResultsMann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p = 0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p = 0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p = 0.01).ConclusionsThese findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.

Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

Abstract Background Astrocytes respond to injury and disease through a process known as reactive astrogliosis, of which inflammatory signaling is one subset. This inflammatory response is heterogeneous with respect to the inductive stimuli and the afflicted central nervous system region. This is of plausible importance in e.g. traumatic axonal injury (TAI), where lesions in the brainstem carries a particularly poor prognosis. In fact, astrogliotic forebrain astrocytes were recently suggested to cause neuronal death following axotomy. We therefore sought to assess if ventral brainstem- or rostroventral spinal astrocytes exert similar effects on motor neurons in vitro. Methods We derived brainstem/rostroventral spinal astrocyte-like cells (ES-astrocytes) and motor neurons using directed differentiation of mouse embryonic stem cells (ES). We activated the ES-astrocytes using the neurotoxicity-eliciting cytokines interleukin- (IL-) 1α and tumor necrosis factor-(TNF-)α and clinically relevant inflammatory mediators. In co-cultures with reactive ES-astrocytes and motor neurons, we assessed neurotoxic ES-astrocyte activity, similarly to what has previously been shown for other central nervous system (CNS) regions. Results We confirmed the brainstem/rostroventral ES-astrocyte identity using RNA-sequencing, immunocytochemistry, and by comparison with primary subventricular zone-astrocytes. Following cytokine stimulation, the c-Jun N-terminal kinase pathway down-stream product phosphorylated c-Jun was increased, thus demonstrating ES-astrocyte reactivity. These reactive ES-astrocytes conferred a contact-dependent neurotoxic effect upon co-culture with motor neurons. When exposed to IL-1β and IL-6, two neuroinflammatory cytokines found in the cerebrospinal fluid and serum proteome following human severe traumatic brain injury (TBI), ES-astrocytes exerted similar effects on motor neurons. Activation of ES-astrocytes by these cytokines was associated with pathways relating to endoplasmic reticulum stress and altered regulation of MYC. Conclusions Ventral brainstem and rostroventral spinal cord astrocytes differentiated from mouse ES can exert neurotoxic effects in vitro. This highlights how neuroinflammation following CNS lesions can exert region- and cell-specific effects. Our in vitro model system, which uniquely portrays astrocytes and neurons from one niche, allows for a detailed and translationally relevant model system for future studies on how to improve neuronal survival in particularly vulnerable CNS regions following e.g. TAI.

Traumatic axonal injury (TAI) is one of the most common pathological features of severe traumatic brain injury (TBI). Our previous study using proteomics suggested that peripherin (PRPH) should be a potential candidate as a biomarker for TAI diagnosis. This study is to further elucidate the role and association of PRPH with TAI. In the animal study, we performed immunohistochemistry, ELISA and morphological analysis to evaluate PRPH level and distribution following a severe impact. PRPH‐positive regions were widely distributed in the axonal tract throughout the whole brain. Axonal injuries with PRPH inclusion were observed post‐TBI. Besides, PRPH was significantly increased in both cerebral spinal fluid and plasma at the early phase post‐TBI. Colocalization analysis based on microscopy revealed that PRPH represents an immunohistological biomarker in the neuropathological diagnosis of TAI. Brain samples from patients with TBI were included to further test whether PRPH is feasible in the real practice of neuropathology. Immunohistochemistry of PRPH, NFH, APP and NFL on human brain tissues further confirmed PRPH as an immunohistological biomarker that could be applied in practice. Collectively, we conclude that PRPH mirrors the cytoskeleton injury of axons and could represent a neuropathological biomarker for TAI. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) triggers progressive neurodegeneration resulting in brain atrophy that continues months‐to‐years following injury. However, a comprehensive characterization of the spatial and temporal evolution of TBI‐related brain atrophy remains incomplete. Utilizing a sensitive and unbiased morphometry analysis pipeline optimized for detecting longitudinal changes, we analyzed a sample consisting of 37 individuals with moderate‐severe TBI who had primarily high‐velocity and high‐impact injury mechanisms. They were scanned up to three times during the first year after injury (3 months, 6 months, and 12 months post‐injury) and compared with 33 demographically matched controls who were scanned once. Individuals with TBI already showed cortical thinning in frontal and temporal regions and reduced volume in the bilateral thalami at 3 months post‐injury. Longitudinally, only a subset of cortical regions in the parietal and occipital lobes showed continued atrophy from 3 to 12 months post‐injury. Additionally, cortical white matter volume and nearly all deep gray matter structures exhibited progressive atrophy over this period. Finally, we found that disproportionate atrophy of cortex along sulci relative to gyri, an emerging morphometric marker of chronic TBI, was present as early as 3 month post‐injury. In parallel, neurocognitive functioning largely recovered during this period despite this pervasive atrophy. Our findings demonstrate msTBI results in characteristic progressive neurodegeneration patterns that are divergent across regions and scale with the severity of injury. Future clinical research using atrophy during the first year of TBI as a biomarker of neurodegeneration should consider the spatiotemporal profile of atrophy described in this study. [ABSTRACT FROM AUTHOR]

Leukemia inhibitory factor (LIF) is a neuroprotective cytokine that is essential for appropriate glial responses, remyelination, and preservation of neuronal conductance after injury. The intranasal route for delivery of therapeutics to the central nervous system is of particular interest given that it bypasses the blood?brain barrier and peripheral clearance systems. We explored the possibility that LIF might improve neurological function when administered intranasally during the acute phase in a pediatric model of mild traumatic brain injury (mTBI). We tested two doses of LIF and evaluated behavioral outcomes. Here, we show that acute 40-ng intranasal LIF treatment twice a day for 3 days attenuates astrogliosis and microgliosis, protects against axonal damage, significantly improves sensorimotor function, and is well tolerated without detrimental effects on growth. Altogether, our studies provide pre-clinical evidence for the use of acute intranasal LIF treatment as a viable therapeutic for pediatric cases of mTBIs.

Abstract Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects.

Background: Astrocytes respond to injury and disease through a process known as reactive astrogliosis, of which inflammatory signaling is one subset. This inflammatory response is heterogeneous with respect to the inductive stimuli and the afflicted central nervous system region. This is of plausible importance in e.g. traumatic axonal injury (TAI), where lesions in the brainstem carries a particularly poor prognosis. In fact, astrogliotic forebrain astrocytes were recently suggested to cause neuronal death following axotomy. We therefore sought to assess if ventral brainstem- or rostroventral spinal astrocytes exert similar effects on motor neurons in vitro. Methods: We derived brainstem/rostroventral spinal astrocyte-like cells (ES-astrocytes) and motor neurons using directed differentiation of mouse embryonic stem cells (ES). We activated the ES-astrocytes using the neurotoxicity-eliciting cytokines interleukin- (IL-) 1α and tumor necrosis factor-(TNF-)α and clinically relevant inflammatory mediators. In co-cultures with reactive ES-astrocytes and motor neurons, we assessed neurotoxic ES-astrocyte activity, similarly to what has previously been shown for other central nervous system (CNS) regions. Results: We confirmed the brainstem/rostroventral ES-astrocyte identity using RNA-sequencing, immunocytochemistry, and by comparison with primary subventricular zone-astrocytes. Following cytokine stimulation, the c-Jun N-terminal kinase pathway down-stream product phosphorylated c-Jun was increased, thus demonstrating ES-astrocyte reactivity. These reactive ES-astrocytes conferred a contact-dependent neurotoxic effect upon co-culture with motor neurons. When exposed to IL-1β and IL-6, two neuroinflammatory cytokines found in the cerebrospinal fluid and serum proteome following human severe traumatic brain injury (TBI), ES-astrocytes exerted similar effects on motor neurons. Activation of ES-astrocytes by these cytokines was associated with pathways relating to endoplasmic reticulum stress and altered regulation of MYC. Conclusions: Ventral brainstem and rostroventral spinal cord astrocytes differentiated from mouse ES can exert neurotoxic effects in vitro. This highlights how neuroinflammation following CNS lesions can exert region- and cell-specific effects. Our in vitro model system, which uniquely portrays astrocytes and neurons from one niche, allows for a detailed and translationally relevant model system for future studies on how to improve neuronal survival in particularly vulnerable CNS regions following e.g. TAI. [ABSTRACT FROM AUTHOR]

BackgroundTraumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy. Moreover, we showed that DLK and LZK are the major upstream triggers for JUN N-terminal kinase (JNK) signaling following total axonal transection. However, the degree to which DLK/LZK are involved in TAI/TBI is unknown.MethodsHere we used the impact acceleration (IA) model of diffuse TBI, which produces TAI in the visual system, and complementary genetic and pharmacologic approaches to disrupt DLK and LZK, and explored whether DLK and LZK play a role in RGC perikaryal and axonal degeneration in response to TAI.ResultsOur findings show that the IA model activates DLK/JNK/JUN signaling but, in contrast to axotomy, many RGCs are able to recover from the injury and terminate the activation of the pathway. Moreover, while DLK disruption is sufficient to suppress JUN phosphorylation, combined DLK and LZK inhibition is required to prevent RGC cell death. Finally, we show that the FDA-approved protein kinase inhibitor, sunitinib, which has activity against DLK and LZK, is able to produce similar increases in RGC survival.ConclusionThe mitogen-activated kinase kinase kinases (MAP3Ks), DLK and LZK, participate in cell death signaling of CNS neurons in response to TBI. Moreover, sustained pharmacologic inhibition of DLK is neuroprotective, an effect creating an opportunity to potentially translate these findings to patients with TBI.

Abstract Background Magnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings. Methods Data were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS)

Traumatic axonal injury (TAI) accounts for a large proportion of the mortality of traumatic brain injury (TBI). The diagnosis of TAI is currently of limited use for medicolegal purposes. It is known that axons in TAI are diffusely damaged by secondary processes other than direct head injury. However, the physiopathological mechanism of TAI is still elusive. The present study used RGD peptide, an antagonist of the mechanotransduction protein integrin, to explore the role of integrin-transmitted mechanical signalling in the pathogenesis of rat TAI. The rats were subjected to a linearly accelerating load, and changes in beta-amyloid precursor protein (β-APP) expression, skeleton ultrastructure, skeleton protein neurofilament light (NF-L), and α-tubulin in the brainstem were observed, indicating that RGD could relieve the severity of axonal injury in TAI rats. In addition, the expression of β-integrin was stronger and centralized in the brainstem of the deceased died from TAI compared to other nonviolent causes. This study examined the pathophysiology and biomechanics of TAI and assessed the role of integrin in the injury of microtubules and neurofilaments in TAI. Thus, we propose that integrin-mediated cytoskeletal injury plays an important role in TAI and that integrin has the potential as a biomarker for TAI. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) has high morbidity and poor prognosis and imposes a serious socioeconomic burden. Traumatic axonal injury (TAI), which is one of the common pathological changes in the primary injury of TBI, is often caused by the external force to the head that causes the white matter bundles to generate shear stress and tension; resulting in tissue damage and leading to the cytoskeletal disorder. At present, the forensic pathological diagnosis of TAI-caused death is still a difficult problem. Most of the TAI biomarkers studied are used for the prediction, evaluation, and prognosis of TAI in the living state. The research subjects are mainly humans in the living state or model animals, which are not suitable for the postmortem diagnosis of TAI. In addition, there is still a lack of recognized indicators for the autopsy pathological diagnosis of TAI. Different diagnostic methods and markers have their limitations, and there is a lack of systematic research and summary of autopsy diagnostic markers of TAI. Therefore, this study mainly summarizes the pathological mechanism, common methods, techniques of postmortem diagnosis, and corresponding biomarkers of TAI, and puts forward the strategies for postmortem diagnosis of TAI for forensic cases with different survival times, which is of great significance to forensic pathological diagnosis. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem. The majority of cases were characterized by fractures of the cranium at or about the impact site, extensive subarachnoid hemorrhages, coup and contrecoup contusions, and primarily diffuse axonal and vascular lesions throughout the cerebrum, particularly in the brainstem. Absence of spontaneous respiration that was encountered frequently was associated with both severity of impact and the severity of brainstem axonal and vascular lesions. A focused regional examination of brainstem pathology indicated a link between adverse outcomes and diffuse axonal lesions within the medial medulla or vascular lesions within the anteroventral brainstem, a pattern suggesting that injury to brainstem respiratory centers may play a role in apnea following BHBT. In addition, while the overall burden of diffuse axonal and vascular pathologies correlated with each other, we found minimal overlap in their regional distribution. Our findings indicate that high-energy, blunt-force impact TBI causes diffuse lesions in axons and blood vessels associated with poor outcomes. They also suggest that axons and vessels may have distinct responses to tissue deformation and that commonly used markers of vascular pathology, for example, in diagnostic radiology, cannot be used as direct surrogates of diffuse axonal injury. In concert, our study underscores the role of regional axonal and vascular injuries in the brainstem in acute respiratory decompensation after high-rate blunt TBI, even in the presence of head protection; it also emphasizes the importance of detailed clinicopathological work in complex brains in the field of TBI.

New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 ± 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 ± 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.1 ± 7.9) and accurately discriminated between patients and controls (AUC: 0.91). The number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients, respectively), consistent with prior histopathological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe TBI.

Background: Magnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings.Methods: Data were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS) < 13 or patient intubated with unrecorded pre-intubation GCS, CT with Marshall score < 3, serum biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1) sampled ≤ 24 h of injury, MRI < 30 days of injury. The degree of axonal injury on MRI was graded using the Adams-Gentry classification. The association between serum concentrations of biomarkers and Adams-Gentry stage was assessed and the optimum threshold concentration identified, assuming different minimum sensitivities for the detection of brainstem injury (Adams-Gentry stage 3). A cost-benefit analysis for the USA and UK health care settings was also performed.Results: Among 65 included patients (30 moderate-severe, 35 unrecorded) axonal injury was detected in 54 (83%) and brainstem involvement in 33 (51%). In patients with moderate-severe TBI, brainstem injury was associated with higher concentrations of NSE, Tau, UCH-L1 and GFAP. If the clinician did not want to miss any brainstem injury, NSE could have avoided MRI transfers in up to 20% of patients. If a 94% sensitivity was accepted considering potential transfer-related complications, GFAP could have avoided 30% of transfers. There was no added net cost, with savings up to £99 (UK) or $612 (US). No associations between proteins and axonal injury were found in intubated patients without a recorded pre-intubation GCS.Conclusions: Serum protein biomarkers show potential to safely reduce the number of transfers to MRI in critically ill patients with moderate-severe TBI at no added cost. [ABSTRACT FROM AUTHOR]

Present review paper aims to understand role of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in diagnosis of traumatic axonal injury (TAI), induced by head trauma, in individual patients with a concussion or mild traumatic brain injury (mTBI). Precise information on presence and severity of TAI in brain is necessary for determining appropriate therapeutic strategies. Several hundred DTI-based studies have reported TAI in concussion or mTBI. Majority of these DTI-based studies have been performed in a group of patients, whereas case studies that have reported TAI in individual patients with a concussion or mTBI are fewer. Summary of these DTI-based studies for individual patients is as follows: DTI can be used as a non-invasive tool for determining presence and severity of TAI in individual patients with concussion or mTBI. However, for diagnosis of TAI in an individual patient, several conditions are required to be met: no past history of head trauma, presence of possible conditions for TAI occurrence during head trauma, development of new clinical features after head trauma, and DTI observed abnormality of a neural structure that coincides with a newly developed clinical feature. However, further studies for a more precise diagnosis of TAI in individual patients should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Only in 7–15% of patients with mild traumatic brain injury (mTBI), traumatic CT-abnormalities are found. Nevertheless, 40% of mTBI patients suffer from posttraumatic complaints not resolving after 6 months. We discuss the ability of susceptibility-weighted imaging (SWI), sensitive for microbleeds, to detect more subtle brain abnormalities. Summary: After a search on PubMed, we selected 15 studies on SWI in adult mTBI patients; 11 studies on 3T MRI, and 4 studies on 1.5T MRI. All 1.5T studies showed that, compared to T2, gradient echo, diffusion-weighted imaging, or fluid-attenuated inversion recovery sequences, SWI is more sensitive for microbleeds. Only two 1.5T studies described the association between SWI findings and outcome. In 3 of the 4 studies, no control group was present. The mean number of microbleeds varied from 3.2 to 6.4 per patient. In the 3T studies, the percentage of patients with traumatic microbleeds varied from 5.7 to 28.8%, compared to 0–13.3% in normal controls. Microbleeds were particularly located subcortical or juxtacortical. The number of microbleeds in mTBI varied from 1 to 10 per patient. mTBI patients with microbleeds appeared to have higher symptom severity at 12 months and perform worse on tests of psychomotor speed and speed of information processing after 3 and 12 months, compared to mTBI patients without microbleeds. Key Messages: There is some evidence that traumatic microbleeds predict cognitive outcome and persistent posttraumatic complaints in patients with mTBI. [ABSTRACT FROM AUTHOR]

Abstract Background We report on a patient with a mild traumatic brain injury (TBI) who developed abdominal pain due to spinothalamic tract (STT) injuries revealed by diffusion tensor tractography (DTT). Case presentation A 53-year-old female patient suffered head trauma resulting from a backward fall. While bathing at a public bathhouse, she fell backward and struck the occipital area of her head against the floor. After the head trauma, she experienced pain in the abdomen and in both hands and feet. She underwent evaluations including conventional brain MRI, abdominal and pelvic ultrasonography, and stomach and intestine endoscopy. No abnormality was observed in her brain or abdomen. In addition, her abdominal pain had not been relieved by medical management. When she came to our hospital 4 years after the head trauma, her pain characteristics and severity were as follows: intermittent pain without allodynia or hyperalgesia; squeezing and warm creeping-like pain in the abdomen (visual analog scale score: 7); tingling pain in both hands and feet (visual analog scale score: 7). She was prescribed pregabalin and gabapentin, and her abdominal and limb pain was well-controlled at a tolerable level. On DTT 4 years after head trauma, the upper portion of the spinothalamic tracts (STTs) in both hemispheres showed partial tearing. Discussion and conclusions Injury of the STT was demonstrated by using DTT in a patient who showed abdominal pain that was refractory to medical management following mild TBI. Our results suggest that central pain due to STT injury might be suspected in patients with abdominal pain that is refractory to medical management following TBI.

Studies show conflicting results regarding the prognostic significance of traumatic axonal injuries (TAI) in patients with traumatic brain injury (TBI). Therefore, we documented the presence of TAI in several brain regions, using different magnetic resonance imaging (MRI) sequences, and assessed their association to patient outcomes using machine learning. Further, we created a novel MRI-based TAI grading system with the goal of improving outcome prediction in TBI. We subsequently evaluated the performance of several TAI grading systems. We used a genetic algorithm to identify TAI that distinguish favorable from unfavorable outcomes. We assessed the discriminatory performance (area under the curve [AUC]) and goodness-of-fit (Nagelkerke pseudo-R2) of the novel Stockholm MRI grading system and the TAI grading systems of Adams and associates, Firsching and coworkers. and Abu Hamdeh and colleagues, using both univariate and multi-variate logistic regression. The dichotomized Glasgow Outcome Scale was considered the primary outcome. We examined the MRI scans of 351 critically ill patients with TBI. The TAI in several brain regions, such as the midbrain tegmentum, were strongly associated with unfavorable outcomes. The Stockholm MRI grading system exhibited the highest AUC (0.72 vs. 0.68–0.69) and Nagelkerke pseudo-R2 (0.21 vs. 0.14–0.15) values of all TAI grading systems. These differences in model performance, however, were not statistically significant (DeLong test, p > 0.05). Further, all included TAI grading systems improved outcome prediction relative to established outcome predictors of TBI, such as the Glasgow Coma Scale (likelihood-ratio test, p < 0.001). Our findings suggest that the detection of TAI using MRI is a valuable addition to prognostication in TBI. [ABSTRACT FROM AUTHOR]

Abstract Background Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy. Moreover, we showed that DLK and LZK are the major upstream triggers for JUN N-terminal kinase (JNK) signaling following total axonal transection. However, the degree to which DLK/LZK are involved in TAI/TBI is unknown. Methods Here we used the impact acceleration (IA) model of diffuse TBI, which produces TAI in the visual system, and complementary genetic and pharmacologic approaches to disrupt DLK and LZK, and explored whether DLK and LZK play a role in RGC perikaryal and axonal degeneration in response to TAI. Results Our findings show that the IA model activates DLK/JNK/JUN signaling but, in contrast to axotomy, many RGCs are able to recover from the injury and terminate the activation of the pathway. Moreover, while DLK disruption is sufficient to suppress JUN phosphorylation, combined DLK and LZK inhibition is required to prevent RGC cell death. Finally, we show that the FDA-approved protein kinase inhibitor, sunitinib, which has activity against DLK and LZK, is able to produce similar increases in RGC survival. Conclusion The mitogen-activated kinase kinase kinases (MAP3Ks), DLK and LZK, participate in cell death signaling of CNS neurons in response to TBI. Moreover, sustained pharmacologic inhibition of DLK is neuroprotective, an effect creating an opportunity to potentially translate these findings to patients with TBI.

Traumatic axonal injury (TAI) is a critical public health issue with its pathogenesis remaining largely elusive. Finite element (FE) head models are promising tools to bridge the gap between mechanical insult, localized brain response, and resultant injury. In particular, the FE-derived deformation along the direction of white matter (WM) tracts (i.e., tract-oriented strain) has been shown to be an appropriate predictor for TAI. The evolution of fiber orientation in time during the impact and its potential influence on the tract-oriented strain remains unknown, however. To address this question, the present study leveraged an embedded element approach to track real-time fiber orientation during impacts. A new scheme to calculate the tract-oriented strain was proposed by projecting the strain tensors from pre-computed simulations along the temporal fiber direction instead of its static counterpart directly obtained from diffuse tensor imaging. The results revealed that incorporating the real-time fiber orientation not only altered the direction but also amplified the magnitude of the tract-oriented strain, resulting in a generally more extended distribution and a larger volume ratio of WM exposed to high deformation along fiber tracts. These effects were exacerbated with the impact severities characterized by the acceleration magnitudes. Results of this study provide insights into how best to incorporate fiber orientation in head injury models and derive the WM tract-oriented deformation from computational simulations, which is important for furthering our understanding of the underlying mechanisms of TAI. [ABSTRACT FROM AUTHOR]

Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury. [ABSTRACT FROM AUTHOR]

Axonal injury is a major contributor to the clinical symptomatology in patients with traumatic brain injury. Conventional neuroradiological tools, such as CT and MRI, are insensitive to diffuse axonal injury (DAI) caused by trauma. Diffusion tensor MRI parameters may change in DAI lesions; however, the nature of these changes is inconsistent. Multidimensional MRI is an emerging approach that combines T1, T2, and diffusion, and replaces voxel-averaged values with distributions, which allows selective isolation of specific potential abnormal components. By performing a combined post-mortem multidimensional MRI and histopathology study, we aimed to investigate T1-T2-diffusion changes linked to DAI and to define their histopathological correlates. Corpora callosa derived from eight subjects who had sustained traumatic brain injury, and three control brain donors underwent post-mortem ex vivo MRI at 7 T. Multidimensional, diffusion tensor, and quantitative T1 and T2 MRI data were acquired and processed. Following MRI acquisition, slices from the same tissue were tested for amyloid precursor protein (APP) immunoreactivity to define DAI severity. A robust image co-registration method was applied to accurately match MRI-derived parameters and histopathology, after which 12 regions of interest per tissue block were selected based on APP density, but blind to MRI. We identified abnormal multidimensional T1-T2, diffusion-T2, and diffusion-T1 components that are strongly associated with DAI and used them to generate axonal injury images. We found that compared to control white matter, mild and severe DAI lesions contained significantly larger abnormal T1-T2 component (P = 0.005 and P < 0.001, respectively), and significantly larger abnormal diffusion-T2 component (P = 0.005 and P < 0.001, respectively). Furthermore, within patients with traumatic brain injury the multidimensional MRI biomarkers differentiated normal-appearing white matter from mild and severe DAI lesions, with significantly larger abnormal T1-T2 and diffusion-T2 components (P = 0.003 and P < 0.001, respectively, for T1-T2; P = 0.022 and P < 0.001, respectively, for diffusion-T2). Conversely, none of the conventional quantitative MRI parameters were able to differentiate lesions and normal-appearing white matter. Lastly, we found that the abnormal T1-T2, diffusion-T1, and diffusion-T2 components and their axonal damage images were strongly correlated with quantitative APP staining (r = 0.876, P < 0.001; r = 0.727, P < 0.001; and r = 0.743, P < 0.001, respectively), while producing negligible intensities in grey matter and in normal-appearing white matter. These results suggest that multidimensional MRI may provide non-invasive biomarkers for detection of DAI, which is the pathological substrate for neurological disorders ranging from concussion to severe traumatic brain injury. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic axonal injury (TAI) is a condition defined as multiple, scattered, small hemorrhagic, and/or non-hemorrhagic lesions, alongside brain swelling, in a more confined white matter distribution on imaging studies, together with impaired axoplasmic transport, axonal swelling, and disconnection after traumatic brain injury (TBI). Ever since its description in the 1980s and the grading system by Adams et al., our understanding of the processes behind this entity has increased. Methods: We performed a scoping systematic, narrative review by interrogating Ovid MEDLINE, Embase, and Google Scholar on the pathophysiology, biomarkers, and diagnostic tools of TAI patients until July 2020. Results: We underline the misuse of the Adams classification on MRI without proper validation studies, and highlight the hiatus in the scientific literature and areas needing more research. In the past, the theory behind the pathophysiology relied on the inertial force exerted on the brain matter after severe TBI inducing a primary axotomy. This theory has now been partially abandoned in favor of a more refined theory involving biochemical processes such as protein cleavage and DNA breakdown, ultimately leading to an inflammation cascade and cell apoptosis, a process now described as secondary axotomy. Conclusion: The difference in TAI definitions makes the comparison of studies that report outcomes, treatments, and prognostic factors a daunting task. An even more difficult task is isolating the outcomes of isolated TAI from the outcomes of severe TBI in general. Targeted bench-to-bedside studies are required in order to uncover further pathways involved in the pathophysiology of TAI and, ideally, new treatments. [ABSTRACT FROM AUTHOR]

Craniocerebral trauma is the most common cause of death and post-traumatic disability in people under 45 years of age. In Romania, the annual incidence shows, that for every 100,000 inhabitants, there are 300 cases of craniocerebral trauma that require specialized medical assistance. Craniocerebral traumas are the most common types of traumas encountered in current forensic practice. Research on the mechanisms of injury, the timing of head trauma and the establishment of causes of death remain relevant. Establishing the traumatic moment implies both the distinction between pre-mortem and post-mortem injuries but also considerations regarding the post-traumatic survival interval. Regarding the elucidation of the moment of occurrence of the craniocerebral trauma from the forensic point of view, a satisfactory result has not been reached so far. The classic hypothesis regarding the development of traumatic brain injuries shows that they are the result of primary traumatic injuries due to cell necrosis combined with the inflammatory brain response that causes secondary brain injuries. It was considered that post-traumatic neuronal losses are strictly due to necrosis and inflammation, and cellular apoptosis being a physiological process, does not play a role in this process. Due to recent experimental data, brain cell apoptosis has begun to be reevaluated. The pathophysiology of traumatic brain injury is far from being fully understood, with the idea that apoptosis would play an even more important role than originally thought. Specifically, damaged brain cells release neuromodulatory substances that can lead to late-onset neuronal damage long after necrotic and inflammatory brain phenomena have ceased to act. These neuronal cell losses are responsible for the development of various neurological deficits and post-traumatic sequelae. [ABSTRACT FROM AUTHOR]

Background: We report on a patient with a mild traumatic brain injury (TBI) who developed abdominal pain due to spinothalamic tract (STT) injuries revealed by diffusion tensor tractography (DTT).Case Presentation: A 53-year-old female patient suffered head trauma resulting from a backward fall. While bathing at a public bathhouse, she fell backward and struck the occipital area of her head against the floor. After the head trauma, she experienced pain in the abdomen and in both hands and feet. She underwent evaluations including conventional brain MRI, abdominal and pelvic ultrasonography, and stomach and intestine endoscopy. No abnormality was observed in her brain or abdomen. In addition, her abdominal pain had not been relieved by medical management. When she came to our hospital 4 years after the head trauma, her pain characteristics and severity were as follows: intermittent pain without allodynia or hyperalgesia; squeezing and warm creeping-like pain in the abdomen (visual analog scale score: 7); tingling pain in both hands and feet (visual analog scale score: 7). She was prescribed pregabalin and gabapentin, and her abdominal and limb pain was well-controlled at a tolerable level. On DTT 4 years after head trauma, the upper portion of the spinothalamic tracts (STTs) in both hemispheres showed partial tearing.Discussion and Conclusions: Injury of the STT was demonstrated by using DTT in a patient who showed abdominal pain that was refractory to medical management following mild TBI. Our results suggest that central pain due to STT injury might be suspected in patients with abdominal pain that is refractory to medical management following TBI. [ABSTRACT FROM AUTHOR]

Contemporary biomechanical modeling of traumatic brain injury (TBI) focuses on either the global brain as an organ or a representative tiny section of a single axon. In addition, while it is common for a global brain model to employ real-world impacts as input, axonal injury models have largely been limited to inputs of either tension or compression with assumed peak strain and strain rate. These major gaps between global and microscale modeling preclude a systematic and mechanistic investigation of how tissue strain from impact leads to downstream axonal damage throughout the white matter. In this study, a unique subject-specific multimodality dataset from a male ice-hockey player sustaining a diagnosed concussion is used to establish an efficient and scalable computational pipeline. It is then employed to derive voxelized brain deformation, maximum principal strains and white matter fiber strains, and finally, to produce diverse fiber strain profiles of various shapes in temporal history necessary for the development and application of a deep learning axonal injury model in the future. The pipeline employs a structured, voxelized representation of brain deformation with adjustable spatial resolution independent of model mesh resolution. The method can be easily extended to other head impacts or individuals. The framework established in this work is critical for enabling large-scale (i.e., across the entire white matter region, head impacts, and individuals) and multiscale (i.e., from organ to cell length scales) modeling for the investigation of traumatic axonal injury (TAI) triggering mechanisms. Ultimately, these efforts could enhance the assessment of concussion risks and design of protective headgear. Therefore, this work contributes to improved strategies for concussion detection, mitigation, and prevention., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Severe traumatic brain injury (TBI) produces shearing forces on long-range axons and brain vessels, causing axonal and vascular injury. To examine whether microbleeds and axonal injury colocalize after TBI, we performed whole-brain susceptibility-weighted imaging (SWI) and diffusion tensor imaging (DTI) in 14 patients during the subacute phase after severe TBI. SWI was used to determine the number and volumes of microbleeds in five brain regions: the frontotemporal lobe; parieto-occipital lobe; midsagittal region (cingular cortex, parasagittal white matter, and corpus callosum); deep nuclei (basal ganglia and thalamus); and brainstem. Averaged fractional anisotropy (FA) and mean diffusivity (MD) were measured to assess microstructural changes in the normal appearing white matter attributed to axonal injury in the same five regions. Regional expressions of microbleeds and microstructure were used in a partial least-squares model to predict the impairment of consciousness in the subacute stage after TBI as measured with the Coma Recovery Scale-Revised (CRS-R). Only in the midsagittal region, the expression of microbleeds was correlated with regional changes in microstructure as revealed by DTI. Microbleeds and microstructural DTI-based metrics of deep, but not superficial, brain regions were able to predict individual CRS-R. Our results suggest that microbleeds are not strictly related to axonal pathology in other than the midsagittal region. While each measure alone was predictive, the combination of both metrics scaled best with individual CRS-R. Structural alterations in deep brain structures are relevant in terms of determining the severity of impaired consciousness in the acute stage after TBI. [ABSTRACT FROM AUTHOR]

Objective: Radiologic predictors of posttraumatic amnesia (PTA) duration are lacking. We hypothesized that the number and distribution of traumatic microbleeds (TMBs) detected by gradient recalled echo (GRE) magnetic resonance imaging (MRI) predicts PTA duration. Setting: Academic, tertiary medical center. Participants: Adults with traumatic brain injury (TBI). Design: We identified 65 TBI patients with acute GRE MRI. PTA duration was determined with the Galveston Orientation and Amnesia Test, Orientation Log, or chart review. TMBs were identified within memory regions (hippocampus, corpus callosum, fornix, thalamus, and temporal lobe) and control regions (internal capsule and global). Regression tree analysis was performed to identify radiologic predictors of PTA duration, controlling for clinical PTA predictors. Main Measures: TMB distribution, PTA duration. Results: Sixteen patients (25%) had complicated mild, 4 (6%) had moderate, and 45 (69%) had severe TBI. Median PTA duration was 43 days (range, 0-240 days). In univariate analysis, PTA duration correlated with TMBs in the corpus callosum (R = 0.29, P = .02) and admission Glasgow Coma Scale (GCS) score (R =-0.34, P = .01). In multivariate regression analysis, admission GCS score was the only significant contributor to PTA duration. However, in regression tree analysis, hippocampal TMBs, callosal TMBs, age, and admission GCS score explained 26% of PTA duration variance and distinguished a subgroup with prolonged PTA. Conclusions: Hippocampal and callosal TMBs are potential radiologic predictors of PTA duration. [ABSTRACT FROM AUTHOR]

We describe a diffusion tensor tractography-based diagnostic approach to traumatic axonal injury of the optic radiation in a patient who showed visual field defect after mild traumatic brain injury. A 43-yr-old female patient experienced head trauma during a motor vehicle accident. After the head trauma, she noticed visual disturbance. peripheral field defects were detected in both eyes on the Humphrey visual field test. After diffusion tensor tractography-based reconstruction of the optic radiation, We determined the fractional anisotropy and fiber number of each whole optic radiation. Four regions of interest were placed on the optic radiations based on diffusion tensor tractography configuration. The right optic radiation showed narrowing, and the left optic radiation revealed partial tearing in the posterior portion. The fiber number of the right optic radiation was more than two standard deviations lower than the control mean. The fractional anisotropy values of the regions of interest 2 (the narrowed area of the right optic radiation) and regions of interest 3 (the partially torn area of the left optic radiation) were more than two standard deviations lower than the control mean. Our results suggest that analysis of the configuration and parameters of the optic radiation based on three-dimensionally reconstructed diffusion tensor tractography results is a useful technique in the detection of traumatic axonal injury of the optic radiation in individual patients with mild traumatic brain injury. [ABSTRACT FROM AUTHOR]

This paper reports a mechanism for corticospinal tract injury in a patient with hemiplegia following traumatic brain injury (TBI) based on diffusion tensor tractography (DTT) finding. A 73-year-old male with TBI resulting from a fall, without medical history, was diagnosed as having left convexity epidural hematoma (EDH). He underwent craniotomy and suffered motor weakness on the right side of the body. Two weeks after onset, he was transferred to a rehabilitation department with an alerted level of consciousness. Four weeks after onset, his motor functions were grade 1 by the Medical Research Council’s (MRC) standards in the right-side limbs and grade 4 in the left-side limbs. The result of DTT using the different regions of interest (ROIs) showed that most of the right corticospinal tract (CST) did not reach the cerebral cortex around where the EDH was located, and when the ROI was placed on upper pons, a disconnection of the CST was shown and a connection of the CST in ROI with the middle pons appeared. However, the right CST was connected to the cerebral cortex below the pons regardless of ROI. This study is the first report to use DTT to detect that the discontinuation of the left CST in the cerebral cortex and injury lesions below the lower pons and between the upper and lower pons are responsible for motor weakness in a patient.

Objectives: We report on a patient with sensorineural hearing loss from injury of the auditory radiation following mild TBI, diagnosed by diffusion tensor tractography (DTT). Method: A 35-year-old female patient suffered head trauma. While walking in a crosswalk, her left lumbar area was hit by a turning car and she fell to the ground. She was pulled behind the car for several meters while her occipital area repeatedly hit the ground. She complained that she began to feel hearing impairment approximately two weeks after the head trauma, that aggravated over time. Approximately 1.5 years after head trauma, when she visited a university hospital for evaluation of the brain, she complained of severe hearing impairment. To characterize the patient's hearing loss, pure tone audiometry was evaluated in a sound proof room to screen her hearing status for the frequencies 250-8000 Hz. A pure tone threshold in the range of 41-60 dB HL was considered moderate sensorineural hearing loss and 61-80 dB HL severe. However, no abnormality was observed in either ear on physical examination. The patient was diagnosed with bilateral moderate sensorineural hearing loss. Results: On 1.5 year DTT, the auditory radiation was narrowed in both hemispheres. Conclusion: Neural injury of the auditory radiation was demonstrated in a patient with sensorineural hearing loss following mild TBI, using DTT. [ABSTRACT FROM AUTHOR]

Whiplash is a bony or soft tissue injury resulting from an acceleration–deceleration energy transfer in the neck. Although patients with whiplash injury often complain of cerebral symptoms, and previous studies have reported evidence indicating brain injury, such an association has not been clearly elucidated. Traumatic axonal injury (TAI) is tearing of axons due to indirect shearing forces during acceleration, deceleration, and rotation of the brain or to direct head trauma. Diffusion tensor imaging (DTI) has a unique advantage to detect TAI in patients whose conventional brain CT or magnetic resonance imaging (MRI) results were negative following head trauma. Since the introduction of DTI, six studies using diffusion tensor tractography (DTT) based on DTI data have reported TAI in patients with whiplash injury, even though conventional brain CT or MRI results were negative. A precise TAI diagnosis in whiplash patients is clinically important for proper management and prognosis. Among the methods employed to diagnose TAI in the six previous studies, the common diagnostic approach for neural tract TAI in individual patients with whiplash injury were (1) whiplash injury history due to car accident; (2) development of new clinical symptoms and signs after whiplash injury; (3) evidence of neural tract TAI in DTT results, mainly via configurational analysis; and (4) coincidence of newly developed clinical manifestations and the function of injured neural tracts. All six studies were individual patient case studies; therefore, further prospective studies involving larger number of subjects should be encouraged.