Spectrum of Magnetic Resonance Imaging Findings in Acute Pediatric Traumatic Brain Injury - A Pictorial Essay.

Head trauma (HT) in pediatric patients is the number one cause of mortality and morbidity in children. Although computer tomography (CT) imaging provides ample information in assessing acute traumatic brain injuries (TBIs), there are instances when magnetic resonance imaging (MRI) is needed. Due to its high sensitivity in diagnosing small bleeds, MRI offers a well-documented evaluation of primary acute TBIs. Our pictorial essay aims to present some of the latest imaging protocols employed in head trauma and review some practical considerations. Injury mechanisms in accidental HT, lesions' topography, and hematoma signal variability over time are also discussed. Acute primary intra- and extra-axial lesions and their MRI aspect are showcased using images from patients in our hospital. This pictorial essay has an educational purpose. It is intended to guide young emergency and intensive care unit doctors, neurologists, and neurosurgeons in diagnosing acute primary TBIs on MRI while waiting for the official radiologist's report. The presentation focuses on the most frequent traumatic lesions encountered in acute pediatric head trauma.

The prognostic importance of traumatic axonal injury on early MRI: the Trondheim TAI-MRI grading and quantitative models.

OBJECTIVES: We analysed magnetic resonance imaging (MRI) findings after traumatic brain injury (TBI) aiming to improve the grading of traumatic axonal injury (TAI) to better reflect the outcome. METHODS: Four-hundred sixty-three patients (8-70 years) with mild (n = 158), moderate (n = 129), or severe (n = 176) TBI and early MRI were prospectively included. TAI presence, numbers, and volumes at predefined locations were registered on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging, and presence and numbers on T2*GRE/SWI. Presence and volumes of contusions were registered on FLAIR. We assessed the outcome with the Glasgow Outcome Scale Extended. Multivariable logistic and elastic-net regression analyses were performed. RESULTS: The presence of TAI differed between mild (6%), moderate (70%), and severe TBI (95%). In severe TBI, bilateral TAI in mesencephalon or thalami and bilateral TAI in pons predicted worse outcomes and were defined as the worst grades (4 and 5, respectively) in the Trondheim TAI-MRI grading. The Trondheim TAI-MRI grading performed better than the standard TAI grading in severe TBI (pseudo-R2 0.19 vs. 0.16). In moderate-severe TBI, quantitative models including both FLAIR volume of TAI and contusions performed best (pseudo-R2 0.19-0.21). In patients with mild TBI or Glasgow Coma Scale (GCS) score 13, models with the volume of contusions performed best (pseudo-R2 0.25-0.26). CONCLUSIONS: We propose the Trondheim TAI-MRI grading (grades 1-5) with bilateral TAI in mesencephalon or thalami, and bilateral TAI in pons as the worst grades. The predictive value was highest for the quantitative models including FLAIR volume of TAI and contusions (GCS score <13) or FLAIR volume of contusions (GCS score ≥ 13), which emphasise artificial intelligence as a potentially important future tool. CLINICAL RELEVANCE STATEMENT: The Trondheim TAI-MRI grading reflects patient outcomes better in severe TBI than today's standard TAI grading and can be implemented after external validation. The prognostic importance of volumetric models is promising for future use of artificial intelligence technologies. KEY POINTS: Traumatic axonal injury (TAI) is an important injury type in all TBI severities. Studies demonstrating which MRI findings that can serve as future biomarkers are highly warranted. This study proposes the most optimal MRI models for predicting patient outcome at 6 months after TBI; one updated pragmatic model and a volumetric model. The Trondheim TAI-MRI grading, in severe TBI, reflects patient outcome better than today's standard grading of TAI and the prognostic importance of volumetric models in all severities of TBI is promising for future use of AI.

Sex differences in the extent of acute axonal pathologies after experimental concussion.

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.

[Head injuries: What the team physician needs to know]. / Kopfverletzungen: Was der Teamarzt wissen sollte.

A concussion is the mildest form of a mild traumatic brain injury (tbi) and resembles the most prevalent type of sports associated tbi. Diffuse axonal injuries, the main pathophysiological mechanism of concussion, leads to disruption of communication between different brain areas. The resulting clinical symptoms may relate to several clinical domains (cognition, fatigue, anxiety disorders, headaches/migraines or vestibulo-ocular problems), all of which need to be assessed in a clinical screening during an evaluation for possible concussion. Appropriate and consensus-based protocols to conduct clinical exams are provided by the Concussion in Sport Group (Sport Concussion Assessment Tool (SCAT), Sport Concussion Office Assessment Tool (SCOAT)) and should be used in the most up-to-date version. Therapeutically, slowly and incrementally increasing sub symptomatic activation consisting of daily routine activities, aerobic and cognitive exercises should be introduced early after the trauma. Education about concussion should be geared towards target audiences and will then greatly contribute to adherence and acceptance of medical management.

The Effect of Dexamethasone on Neuroinflammation and Cerebral Edema in Rats With Traumatic Brain Injury Combined With Seawater Drowning.

OBJECTIVE: To investigate the effect and mechanism of dexamethasone (DX) on axonal injury after traumatic brain injury (TBI) combined with seawater drowning (SWD) in rats. METHODS: To gain an in-depth understanding of TBI + SWD in rats, we established the compound injury model of rats by the Marmarou method and intratracheal pumping of seawater to simulate the pathological conditions. Rats in the DX group received intraperitoneal injections of DX (1 mg/kg) immediately after injury, and rats in the sham group and TBI + SWD group received intraperitoneal injections of the same amount of normal saline. RESULTS: Hematoxylin-eosin (HE) showed that DX improved matrix looseness, cell swelling, and nuclear condensation 168 hours after injury. Immunohistochemistry (IHC) staining showed that the protein expression of AQP4 was decreased in the DX group compared with the TBI + SWD group from 12 hours to 168 hours after injury. DX decreased the modified neurological severity score (mNSS) significantly at 24 hours and 168 hours after injury (P < 0.05). At 72 h and 168 h after injury, DX significantly lowered the expressions of IL-8 and TNF-α (P < 0.05). CONCLUSION: DX may play a neuroprotective role by reducing cerebral edema and inflammatory response after TBI + SWD injury in rats.

Lesion Frequency Distribution Maps of Traumatic Axonal Injury on Early Magnetic Resonance Imaging After Moderate and Severe Traumatic Brain Injury and Associations to 12 Months Outcome.

Traumatic axonal injury (TAI) is a common finding on magnetic resonance imaging (MRI) in patients with moderate-severe traumatic brain injury (TBI), and the burden of TAI is associated with outcome in this patient group. Lesion mapping offers a way to combine imaging findings from numerous individual patients into common lesion maps where the findings from a whole patient cohort can be assessed. The aim of this study was to evaluate the spatial distribution of TAI lesions on different MRI sequences and its associations to outcome with use of lesion mapping. Included prospectively were 269 patients (8-70 years) with moderate or severe TBI and MRI within six weeks after injury. The TAI lesions were evaluated and manually segmented on fluid-attenuated inversed recovery (FLAIR), diffusion weighted imaging (DWI), and either T2* gradient echo (T2*GRE) or susceptibility weighted imaging (SWI). The segmentations were registered to the Montreal Neurological Institute space and combined to lesion frequency distribution maps. Outcome was assessed with Glasgow Outcome Scale Extended (GOSE) score at 12 months. The frequency and distribution of TAI was assessed qualitatively by visual reading. Univariable associations to outcome were assessed qualitatively by visual reading and also quantitatively with use of voxel-based lesion-symptom mapping (VLSM). The highest frequency of TAI was found in the posterior half of corpus callosum. The frequency of TAI was higher in the frontal and temporal lobes than in the parietal and occipital lobes, and in the upper parts of the brainstem than in the lower. At the group level, all voxels in mesencephalon had TAI on FLAIR. The patients with poorest outcome (GOSE scores ≤4) had higher frequencies of TAI. On VLSM, poor outcome was associated with TAI lesions bilaterally in the splenium, the right side of tectum, tegmental mesencephalon, and pons. In conclusion, we found higher frequency of TAI in posterior corpus callosum, and TAI in splenium, mesencephalon, and pons were associated with poor outcome. If lesion frequency distribution maps containing outcome information based on imaging findings from numerous patients in the future can be compared with the imaging findings from individual patients, it would offer a new tool in the clinical workup and outcome prediction of the patient with TBI.

Prediction for the prognosis of diffuse axonal injury using automated pupillometry.

OBJECTIVE: Previous studies have reported various predictive indicators of diffuse axonal injury (DAI), but no consensus has not been reached. Although the efficiency of automated pupillometry in patients with consciousness disorder has been widely reported, there are few reports of its use in patients with DAI. This study aimed to investigate the significance of pupillary findings in predicting the prognosis of DAI. PATIENTS AND METHODS: We included patients admitted to our center with a diagnosis of DAI from June 1, 2021 to June 30, 2022. Pupillary findings in both eyes were quantitatively measured by automated pupillometry every 2 hours after admission. We statistically examined the correlations between automated pupillometry parameters, the patients' characteristics, and outcomes such as the Glasgow Outcome Scale Extended (GOSE) after 6 months from injury, the time to follow command, and so on. RESULTS: Among 22 patients included in this study, five had oculomotor nerve palsy. Oculomotor nerve palsy was correlated with all outcomes, whereas Marshall computed tomography (CT) classification, Injury severity score (ISS) and DAI grade were correlated with few outcomes. Some of the automated pupillometry parameters were significantly correlated with GOSE at 6 months after injury, and many during the first 24 hours of measurement were correlated with the time to follow command. Most of these results were not affected by adjustment using sedation period, ISS or Marshall CT classification. A subgroup analysis of patients without oculomotor nerve palsy revealed that many of the automated pupillometry parameters during the first 24 hours of measurement were significantly correlated with most of the outcomes. The cutoff values that differentiated a good prognosis (GOSE 5-8) from a poor prognosis (GOSE 1-4) were constriction velocity (CV) 1.43 (AUC = 0.81(0.62-1), p = 0.037) and maximum constriction velocity (MCV) 2.345 (AUC = 0.78 (0.58-0.98), p = 0.04). The cutoff values that differentiated the time to follow command into within 7 days and over 8 days were percentage of constriction 8 (AUC = 0.89 (0.68-1), p = 0.011), CV 0.63 (AUC = 0.92 (0.78-1), p = 0.013), MCV 0.855 (AUC = 0.9 (0.74-1), p = 0.017) and average dilation velocity 0.175 (AUC = 0.95 (0.86-1), p = 0.018). CONCLUSIONS: The present results indicate that pupillary findings in DAI are a strong predictive indicator of the prognosis, and that quantitative measurement of them using automated pupillometry could facilitate enhanced prediction for the prognosis of DAI.

Weight-Drop Method for Inducing Closed Head Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the foremost causes of disability and death globally. Prerequisites for successful therapy of disabilities associated with TBI involved improved knowledge of the neurobiology of TBI, measurement of quantitative changes in recovery dynamics brought about by therapy, and the translation of quantitative methodologies and techniques that were successful in tracking recovery in preclinical models to human TBI. Frequently used animal models of TBI in research and development include controlled cortical impact, fluid percussion injury, blast injury, penetrating blast brain injury, and weight-drop impact acceleration models. Preclinical models of TBI benefit from controlled injury settings and the best prospects for biometric quantification of injury and therapy-induced gradual recovery from disabilities. Impact acceleration closed head TBI paradigm causes diffuse TBI (DTBI) without substantial focal brain lesions in rats. DTBI is linked to a significant rate of death, morbidity, and long-term disability. DTBI is difficult to diagnose at the time of hospitalization with imaging techniques making it challenging to take prompt therapeutic action. The weight-drop method without craniotomy is an impact acceleration closed head DTBI model that is used to induce mild/moderate diffuse brain injuries in rodents. Additionally, we have characterized neuropathological and neurobehavioral outcomes of the weight-drop model without craniotomy for inducing closed head DTBI of graded severity with a range of mass of weights (50-450 gm). This chapter also discusses techniques and protocols for measuring numerous functional disabilities and pathological changes in the brain brought on by DTBI.

Cerebral Infarction Due to Post-traumatic Cerebral Vasospasm in a 12-Year-Old Female.

Cerebral infarction due to post-traumatic cerebral vasospasm is rare. Although some modalities are recommended to detect post-traumatic cerebral vasospasm, its diagnosis remains controversial and challenging. Therefore, in this report, we will use a case report to highlight challenges and to delineate the characteristics of post-traumatic cerebral vasospasm in pediatric patients, including the diagnostic and treatment options. A 12-year-old female was admitted to our hospital following a motor vehicle collision. Her consciousness was severely impaired. Initial computed tomography (CT) revealed an acute subdural hematoma along the tentorium, and a focal subarachnoid hemorrhage was observed in the Sylvian fissure. The patient underwent the insertion of an intracranial pressure sensor and received therapy for increased intracranial pressure (ICP) control under sedation. On the second day, CT angiography (CTA) revealed no signs of arterial abnormality. A patient who is comatose or under sedation has masked neurological symptoms. Thus, new neurological events could only be detected via an intracranial pressure sensor. Her ICP increased on the seventh day, and a CT scan showed a new cerebral infarction in the right middle cerebral artery (MCA) region. We performed decompressive craniectomy to reduce ICP. Postoperative CTA confirmed severe vasospasm in the right MCA. The severe cerebral vasospasm induced the cerebral infarction. Our review suggests that physicians in trauma departments should frequently perform vascular evaluations by CTA, magnetic resonance angiography (MRA), transcranial Doppler ultrasound, or digital subtraction angiography (DSA), especially within two weeks from onset, to detect post-traumatic cerebral vasospasm.

Methylphenidate Ameliorates Behavioural and Neurobiological Deficits in Executive Function for Patients with Chronic Traumatic Brain Injury.

(1) Background: Traumatic brain injury (TBI) often results in cognitive impairments, including in visuospatial planning and executive function. Methylphenidate (MPh) demonstrates potential improvements in several cognitive domains in patients with TBI. The Tower of London (TOL) is a visuospatial planning task used to assess executive function. (2) Methods: Volunteers with a history of TBI (n = 16) participated in a randomised, double-blinded, placebo-controlled, fMRI study to investigate the neurobiological correlates of visuospatial planning and executive function, on and off MPh. (3) Results: Healthy controls (HCs) (n = 18) and patients on placebo (TBI-placebo) differed significantly in reaction time (p < 0.0005) and accuracy (p < 0.0001) when considering all task loads, but especially for high cognitive loads for reaction time (p < 0.001) and accuracy (p < 0.005). Across all task loads, TBI-MPh were more accurate than TBI-placebo (p < 0.05) but remained less accurate than HCs (p < 0.005). TBI-placebo substantially improved in accuracy with MPh administration (TBI-MPh) to a level statistically comparable to HCs at low (p = 0.443) and high (p = 0.175) cognitive loads. Further, individual patients that performed slower on placebo at low cognitive loads were faster with MPh (p < 0.05), while individual patients that performed less accurately on placebo were more accurate with MPh at both high and low cognitive loads (p < 0.005). TBI-placebo showed reduced activity in the bilateral inferior frontal gyri (IFG) and insulae versus HCs. MPh normalised these regional differences. MPh enhanced within-network connectivity (between parietal, striatal, insula, and cerebellar regions) and enhanced beyond-network connectivity (between parietal, thalamic, and cerebellar regions). Finally, individual changes in cerebellar-thalamic (p < 0.005) and cerebellar-parietal (p < 0.05) connectivity with MPh related to individual changes in accuracy with MPh. (4) Conclusions: This work highlights behavioural and neurofunctional differences between HCs and patients with chronic TBI, and that adverse differences may benefit from MPh treatment.

A Case Report Emphasizing an Early Approach in a Patient With Diffuse Axonal Injury.

Diffuse axonal injury (DAI) is a severe and frequently life-altering form of traumatic brain injury that is brought on by forces of rapid acceleration as well as deceleration impacting the brain. DAI primarily stems from mechanical forces that lead to the widespread disruption of axons throughout the brain. Unlike focal injuries that affect a specific brain region, DAI manifests as multifocal axonal damage, often impairing vital neural connections. This injury occurs due to shear and tensile forces during traumatic events, such as car accidents, falls, and sports-related incidents. This current case report includes a 19-year-old male who had a fall from his bike and was hospitalised with brain trauma. A Magnetic resonance imaging (MRI) scan was done, which revealed a case of DAI, and a computed tomography (CT) scan of the brain revealed the extra-calvarial soft tissue swelling in the left parietal region. Small haemorrhagic contusions involved the right ganglio-capsular region. Several integrative techniques, including joint approximation, proprioceptive neuromuscular facilitation (PNF) rhythmic initiation, D1 flexion-extension, and patient education, were used to manage the patient. The patient's development was evaluated using outcome measures, such as the functional independence measure (FIM) and the Glasgow coma scale (GCS). Thus, we conclude that completing physiotherapy exercises consistently helps patients achieve their highest level of functional independence and also enhances their quality of life.

Diffuse axonal injury on magnetic resonance imaging and its relation to neurological outcomes in pediatric traumatic brain injury.

OBJECTIVE: Diffuse axonal injury (DAI), a frequent consequence of pediatric traumatic brain injury (TBI), presents challenges in predicting long-term recovery. This study investigates the relationship between the severity of DAI and neurological outcomes in children. METHODS: We conducted a retrospective analysis of 51 pediatric TBI patients diagnosed with DAI using Adam's classification. Neurological function was assessed at 2, 3, and 6 weeks, and 12 months post-injury using the Pediatric Glasgow Outcome Scale-Extended (PGOSE). RESULTS: PGOSE scores significantly improved over time across all DAI grades, suggesting substantial recovery potential even in initially severe cases. Despite indicating extensive injury, patients with DAI grades II and III demonstrated significant improvement, achieving a good recovery by 12 months. Although the initial Glasgow Coma Scale (GCS) score did not show a statistically significant association with long-term outcomes in our limited sample, these findings suggest that the severity of DAI alone may not fully predict eventual recovery. CONCLUSIONS: Our study highlights the potential for significant neurological recovery in pediatric patients with DAI, emphasizing the importance of long-term follow-up and individualized rehabilitation programs. Further research with larger cohorts and extended follow-up periods is crucial to refine our understanding of the complex relationships between DAI severity, injury mechanisms, and long-term neurological outcomes in children.

The Relationship between Injury Characteristics and Post-Traumatic Recovery after Diffuse Axonal Injury.

BACKGROUND: The diagnosis and prognosis of diffuse axonal injury (DAI) remain challenging. This research aimed to analyze the impact on activities of daily living (ADL), functional outcomes, quality of life (QoL), and the association between lesion severity and DAI location identified through imaging exams. METHODS: This prospective cohort study included 95 patients diagnosed with DAI. Data were collected at admission, three, six, and twelve months post-injury. The associations between variables were evaluated using a mixed-effects model. RESULTS: Functional recovery and QoL improved between three and twelve months after DAI. An interaction was observed between independence in performing ADL and subarachnoid hemorrhage (p = 0.043) and intraventricular hemorrhage (p = 0.012). Additionally, an interaction over time was observed between the Glasgow Outcome Scale (GOS) and DAI severity (p < 0.001), brain lesions (p = 0.014), and the Disability Rating Scale (DRS) with injury in brain hemispheres (p = 0.026) and Adams classification (p = 0.013). Interaction effects over time were observed with the general health perceptions and energy/vitality domains with intraventricular hemorrhage, and the social functioning domain with the obliteration of basal cisterns and Gentry's classification. CONCLUSION: The use of CT in the acute phase of DAI is important for predicting outcomes. The severity and location of DAI are associated with functional outcomes, ADL, and QoL.

Molecular biomarkers of diffuse axonal injury: recent advances and future perspectives.

INTRODUCTION: Diffuse axonal injury (DAI), with high mortality and morbidity both in children and adults, is one of the most severe pathological consequences of traumatic brain injury. Currently, clinical diagnosis, disease assessment, disability identification, and postmortem diagnosis of DAI is mainly limited by the absent of specific molecular biomarkers. AREAS COVERED: In this review, we first introduce the pathophysiology of DAI, summarized the reported biomarkers in previous animal and human studies, and then the molecular biomarkers such as ß-Amyloid precursor protein, neurofilaments, S-100ß, myelin basic protein, tau protein, neuron-specific enolase, Peripherin and Hemopexin for DAI diagnosis is summarized. Finally, we put forward valuable views on the future research direction of diagnostic biomarkers of DAI. EXPERT OPINION: In recent years, the advanced technology has ultimately changed the research of DAI, and the numbers of potential molecular biomarkers was introduced in related studies. We summarized the latest updated information in such studies to provide references for future research and explore the potential pathophysiological mechanism on diffuse axonal injury.

Hyperglycemia disrupted the integrity of the blood-brain barrier following diffuse axonal injury through the sEH/NF-κB pathway.

OBJECTIVES: We aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced-disruption of blood-brain barrier (BBB) integrity after diffuse axonal injury (DAI). METHODS: Rat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium-binding adapter molecule-1, ß-amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. The permeability of blood-brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the nuclear transcription factor kappa B (NF-κB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol-12-myristate-13-acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme-linked immunosorbent assay. RESULTS: Hyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF-κB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF-κB pathway abrogated the protective effects of TPPU on BBB integrity in vitro. CONCLUSIONS: sEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF-κB pathway.

Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA).

Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets-the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20-1.51 kg; 6-9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.

The neuropathology of intimate partner violence.

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd-8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd-9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Radiomics Enhances Diagnostic and Prognostic Value of Diffusion Kurtosis Imaging in Diffuse Axonal Injury.

The aim of our study was to investigate the potential of advanced radiomics in analyzing diffusion kurtosis MRI (DKI) to increase the informativeness of DKI in diffuse axonal injury (DAI). We hypothesized that DKI radiomic features could be used to detect microstructural brain injury and predict outcomes in DAI. The study enrolled 31 patients with DAI (mean age 31.48 ± 11.10 years, 8 (25.8%) female) and 12 healthy volunteers (mean age 33.67 ± 11.06 years, 4 (33.3%) female). A total of 342,300 radiomic features were calculated (2282 features per each combination of 10 parametric DKI maps with 15 ROIs). Our results showed that several radiomic features were capable of distinguishing between healthy and injured brain tissue and accurately predicting outcomes with an accuracy of over 0.9. Advanced DKI radiomic features show high diagnostic and prognostic potential in DAI and may outperform average ROI values in DKI maps.

The Relationship Between Cortical Morphological and Functional Topological Properties and Clinical Manifestations in Patients with Posttraumatic Diffuse Axonal Injury: An Individual Brain Network Study.

To evaluate the altered network topological properties and their clinical relevance in patients with posttraumatic diffuse axonal injury (DAI). Forty-seven participants were recruited in this study, underwent 3D T1-weighted and resting-state functional MRI, and had single-subject morphological brain networks (MBNs) constructed by Kullback-Leibler divergence and functional brain networks (FBNs) constructed by Pearson correlation measurement interregional similarity. The global and regional properties were analyzed and compared using graph theory and network-based statistics (NBS), and the relationship with clinical manifestations was assessed. Compared with those of the healthy subjects, MBNs of patients with DAI showed a higher path length ([Formula: see text]: P = 0.021, [Formula: see text]: P = 0.011), lower clustering ([Formula: see text]: P = 0.002) and less small-worldness ([Formula: see text]: P = 0.002), but there was no significant difference in the global properties of FBNs (P: 0.161-0.216). For nodal properties of MBNs and FBNs, several regions showed significant differences between patients with DAI and healthy controls (HCs) (P < 0.05, FDR corrected). NBS analysis revealed that MBNs have more altered morphological connections in the frontal parietal control network and interhemispheric connections (P < 0.05). DAI-related global or nodal properties of MBNs were correlated with physical disability or dyscognition (P < 0.05/7, with Bonferroni correction), and the alteration of functional topology properties mediates this relationship. Our results suggested that disrupted morphological topology properties, which are mediated by FBNs and correlated with clinical manifestations of DAI, play a critical role in the short-term and medium-term phases after trauma.

Pathological Spectrum and ß-APP Immunoreactivity as a Diagnostic Tool of Diffuse Axonal Injury following Traumatic Brain Injury: A Novel Classification.

Aim Different deposition patterns and grading systems used to define and identify DAI remain discordant and to date these are a challenge in clinical practice. Our main objective was to study the post-mortem axonal changes and develop a grading system to identify DAI on the basis of histopathological and immunoreactive ß-amyloid precursor protein (ß-APP) observations in severe TBI cases. Methods Prospective study with 35 decedents with sTBI (GCS score ≤ 8) was conducted and samples were collected from three different sites-corpus callosum, thalamus and brain stem. Serial sections from each site were stained with hematoxylin and eosin (H&E), and immunohistochemistry (IHC) of ß-APP. Results We developed a grading system based on histopathological characteristics to assess the overall damage of axonal injury. We found maximum histopathological changes in cases with prolonged stay. Corpus callosum showed maximum changes in both gradings. Curiously, we also detected axonal swellings with H&E staining. Usually neglected, the thalamus also showed significant histopathological and immunoreactive changes for sTBI. Conclusion Our study based on histopathological and ß-APP scoring system to define and identify DAI thus facilitates accurate diagnosis of DAI post mortem, which has forensic implications, and may further contribute toward survival and improvement of quality of life of sTBI patients.