Ballooned neurons in semi-recent severe traumatic brain injury.

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.

Prognostic Significance of Magnetic Resonance Imaging in Detecting Diffuse Axonal Injuries: Analysis of Outcomes and Review of Literature.

Background: Diffuse axonal injury (DAI) is the brain injury characterized by extensive lesions in the white matter tracts over a widespread area. DAI is one of the most common and devastating types of traumatic brain injury and a major cause of unconsciousness and persistent vegetative state after head trauma. It occurs in about half of all cases with severe head trauma. Objective: This study was undertaken to evaluate the prognostic significance of magnetic resonance imaging (MRI) in detecting DAI and to determine which clinical factors provide prognostic information in patients with traumatic brain injuries. Materials and Methods: This prospective study was conducted in a tertiary care hospital between April 2017 to May 2019 on 52 patients admitted to the hospital with severe traumatic injuries of the head and clinical diagnosis of DAI. The clinical outcomes and findings of Thecomputerized tomography (CT)/magnetic resonance imaging (MRI) of the brain were assessed at 1 month, 3 months, 6 months, and 1 year on the basis of improvement in Glasgow Coma Scale (GCS), the time required to consciousness, and the duration of hospital stay. The patients were classified into three groups according to the MRI grading classification proposed by Adams. The outcomes at the 6 month follow-up time were dichotomized as non recovered (Glasgow Outcome Scale (GOS) score 1 or 2) or recovered (GOS score 3-5).The following factors were evaluated in relation to outcome: age, admission GCS score, the motor component of the GCS examination at admission and at 24 hours post admission, brainstem injury based on T2-weighted and gradient echo MRI sequences, presence of bilateral brainstem injuries, presence of DAIin the brainstem and the supra tentorial compartment (including the cortex, basal ganglia, and corpus callosum) on both CT and MRI, cerebral contusions, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, and intraventricular hemorrhage. The statistical analysis was performed with x2 between various stages and between patients with and without hemorrhagic DAI. A separate analysis with x2 and Yates' correction was performed after grouping the patients with good recovery and moderate disability against patients with severe disability and vegetative state. Results: The correlation of patients GCS on admission, after 24 hours, and at discharge is statistically significant P < 0.001. Correlation among mean hospital stay in Grade I DAI, Grade II DAI, and Grade III DAI wass statistically significant (f = 70.22, P < 0.001). Correlation among mean time required for consciousness in Grade I DAI, Grade II DAI, and Grade III DAI was statistically significant (f = 181.92, P < 0.001). Based on anatomical location within the brainstem, the poorest outcomes occurred with injury to the medulla- with a 100% mortality rate. Poor outcomes were also associated with any injury to the pons. There was a significant correlation among brainstem injuries that crossed the midline, the motor component of the GCS examination, performed 24 hours after admission and at outcome. The median time to MRI was 1 day (range 0-35 days) among all, but 4 patients underwent MRI within 7 days after admission. Patients who did not recover underwent MRI at an average of 0.8 days after admission, whereas those who recovered underwent MRI at an average of 4.2 days after admission (P = 0.52). To determine if the time from admission to MRI had an influence on results, comparison was made between T2 and patient outcomes in relation to the interval between admission and MRI. Statistical analysis in the group of patients with different DAI stages showed a significant difference (P = 0.013). A statistically significant difference was also found between patients with hemorrhagic and non hemorrhagic DAI (P = 0.004). Conclusion: The current study showed a correlation between the mean time interval to recovery of consciousness in patients with DAI and the severity of injury grading on MRI. Hospital stay required for Grade I DAI was 2-3 weeks, for Grade II DAI was 3-4 weeks, and for Grade III DAI was 7-8 weeks. Apart from the well-known role of the Glasgow Coma Scale (GCS) in the prognosis of the outcome of patients with closed head injury, the presence of hemorrhage in DAI-type lesions and the association with traumatic space occupying lesions are additional poor prognostic signs established in this study. The analysis of outcomes were done for patients admitted with DAI and the current study established that poor outcomes were consistently seen in patients with brainstem injuries and poor results on 24-hour post admission GCS motor examinations.

Axons-on-a-chip for mimicking non-disruptive diffuse axonal injury underlying traumatic brain injury.

Diffuse axonal injury (DAI) is the most severe pathological feature of traumatic brain injury (TBI). However, how primary axonal injury is induced by transient mechanical impacts remains unknown, mainly due to the low temporal and spatial resolution of medical imaging approaches. Here we established an axon-on-a-chip (AoC) model for mimicking DAI and monitoring instant cellular responses. Integrating computational fluid dynamics and microfluidic techniques, DAI was induced by injecting a precisely controlled micro-flux in the transverse direction. The clear correlation between the flow speed of injecting flux and the severity of DAI was elucidated. We next used the AoC to investigate the instant intracellular responses underlying DAI and found that the dynamic formation of focal axonal swellings (FAS) accompanied by Ca2+ surge occurs during the flux. Surprisingly, periodic axonal cytoskeleton disruption also occurs rapidly after the flux. These instant injury responses are spatially restricted to the fluxed axon, not affecting the overall viability of the neuron in the acute stage. Compatible with high-resolution live microscopy, the AoC provides a versatile system to identify early mechanisms underlying DAI, offering a platform for screening effective treatments to alleviate TBI.

Time to Follow Commands in Severe Traumatic Brain Injury Survivors With Favorable Recovery at 2 Years.

BACKGROUND: The recovery of severe traumatic brain injury (TBI) survivors with long-term favorable outlook is understudied. Time to follow commands varies widely in this patient population but has important clinical implications. OBJECTIVE: To (1) evaluate time to follow commands in severe patients with TBI with favorable outcomes, (2) characterize their trajectory of recovery, and (3) identify predictors associated with delayed cognitive improvement. METHODS: Participants were recruited prospectively at a Level I trauma center through the Brain Trauma Research Center from 2003 to 2018. Inclusion criteria were age 16 to 80 years, Glasgow Coma Scale score ≤8 and motor score <6, and Glasgow Outcome Scale-Extended measure ≥4 at 2 years postinjury. RESULTS: In 580 patients, there were 229 (39.5%) deaths and 140 (24.1%) patients had favorable outcomes at 2 years. The mean age was 33.7 ± 14.5 years, median Glasgow Coma Scale was 7 (IQR 6-7), and median Injury Severity Score was 30 (IQR 26-38). The mean time to follow commands was 12.7 ± 11.8 days. On multivariable linear regression, the presence of diffuse axonal injury (B = 9.2 days [4.8, 13.7], P < .0001) or intraventricular hemorrhage (B = 6.4 days [0.5, 12.3], P < .035) was associated with longer time before following commands and patients who developed nosocomial infections (B = 6.5 days [1.6-11.4], P < .01). CONCLUSION: In severe TBI survivors with favorable outcomes, time to follow commands varied widely. Most patients began to follow commands within 2 weeks. Evidence of diffuse axonal injury, intraventricular hemorrhage, and infections can delay cognitive improvement in the acute period. Patients make considerable recovery up to 2 years after their injury.

Vitamin D Deficiency and Prognosis after Traumatic Brain Injury with Intracranial Injury: A Multi-Center Observational Study.

Vitamin D may be important for neuroprotection after traumatic brain injury (TBI) by modifying the inflammatory response. The objective of this study was to evaluate the association between vitamin D deficiency and functional and survival outcomes in patients with TBI and intracranial injury. This study was a prospective multi-center cohort study conducted on adult TBI patients, with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination, admitted to five participating emergency departments (EDs) from December 2018 to June 2020. The study outcomes were good functional recovery at hospital discharge and survival at 6-months after injury. The primary exposure was serum vitamin D deficiency (0-10 ng/mL). Multi-level logistic regression analysis was performed to estimate the association between vitamin D deficiency and the study outcomes. Among 606 patients, 101 (16.7%) patients had vitamin D deficiency at the time of ED arrival. Good functional recovery was observed in 65.2% (395/606) of total population, and this proportion was significantly lower in the vitamin D deficiency group than the non-deficiency group (56.4 vs. 66.9%, p = 0.04, adjusted odds ratio (OR; 95% confidence interval [CI]): 0.56 (0.36-0.88)). Overall survival rate at 6 months after injury was 79.5% (434/546), and patients with vitamin D deficiency had significantly lower likelihood of survival at 6 months than patients without deficiency [75.0 vs. 80.3%, adjusted OR (95% CI): 0.59 (0.39-0.89)]. Vitamin D deficiency is associated with poor functional outcomes at hospital discharge and mortality at 6-months after injury in TBI patients with intracranial hemorrhage or diffuse axonal injury.

An In-Depth Analysis of Brain and Spine Neuroimaging in Children with Abusive Head Trauma: Beyond the Classic Imaging Findings.

BACKGROUND AND PURPOSE: Abusive head trauma is the leading cause of morbidity and mortality in young children. Radiology provides valuable information for this challenging diagnosis, but no single neuroimaging finding is independently diagnostic of abusive head trauma. Our purposes were to describe the prevalence of brain and spine neuroimaging findings and to analyze the association of neuroimaging findings with clinical factors to determine which neuroimaging findings may be used as prognostic indicators. MATERIALS AND METHODS: Children with a confirmed abusive head trauma diagnosis between January 2018 to February 2021 were included in this single-center retrospective study. Patient demographics, survival, Glasgow Coma Scale score on admission, length of hospital stay, and intensive care unit stay were examined. Brain neuroimaging findings were categorized as classic and nonclassic findings. Spine MRIs were also assessed for spinal ligamentous injury, compression fracture, and hemorrhage. The χ2 test or the Wilcoxon rank-sum test was used for the analysis. RESULTS: One hundred two children (male/female ratio: 75:27; average age, 9.49; range, 0.27-53.8 months) were included. Subdural hematoma was the most common (83.3%) classic neuroimaging finding. Bridging vein thrombosis was the most common (30.4%) nonclassic neuroimaging finding. Spinal ligamentous injury was seen in 23/49 patients. Hypoxic-ischemic injury was significantly higher in deceased children (P = .0001). The Glasgow Coma Scale score was lower if hypoxic-ischemic injury (P < .0001) or spinal ligamentous injury were present (P = .017). The length of hospital stay was longer if intraventricular hemorrhage (P = .04), diffuse axonal injury (P = .017), hypoxic-ischemic injury (P = .001), or arterial stroke (P = .0003) was present. The intensive care unit stay was longer if intraventricular hemorrhage (P = .02), diffuse axonal injury (P = .01), hypoxic-ischemic injury (P < .0001), or spinal ligamentous injury (P = .03) was present. CONCLUSIONS: Our results may suggest that a combination of intraventricular hemorrhage, diffuse axonal injury, hypoxic-ischemic injury, arterial stroke, and/or spinal ligamentous injury on neuroimaging at presentation may be used as potential poor prognostic indicators in children with abusive head trauma.

White matter degeneration in diffuse axonal injury and mild traumatic brain injury observed with automatic tractography.

A better understanding of white matter tract damage in patients with diffuse axonal injury (DAI) and mild traumatic brain injury (MTBI) is important to obtain an objective basis for sequelae. The purpose of this study was to clarify the characteristics of white matter tract degeneration in DAI and MTBI using automated tractography. T1-weighted and diffusion tensor imaging (DTI) was performed on seven DAI and seven MTBI patients as well as on nine healthy subjects. Automated probabilistic tractography analysis was performed using FreeSurfer and TRACULA (tracts constrained by underlying anatomy) for the reconstruction of major nerve fibers. We investigated the difference between DTI quantitative values in each white matter nerve fiber between groups and attempted to evaluate the classification accuracy of DAI and MTBI using receiver operator curve analysis. Both DAI and MTBI appeared to exhibit axonal degeneration along the nerve fiber tract in a scattered manner. The mean diffusivity of the ampulla of the corpus callosum was significantly higher in DAI than that in MTBI patients, suggesting axonal degeneration of the corpus callosum in DAI patients. Using mean diffusivity of the right cingulum-angular bundle, DAI and MTBI could be discriminated with an area under the curve of 94%. Both DAI and MTBI exhibited scattered axonal degeneration; however, DAI appeared to exhibit more pronounced axonal degeneration in the ampulla of the corpus callosum than MTBI. Our results suggest that DAI and MTBI can be accurately distinguished using DTI.

Functional plasticity in lateral hypothalamus and its prediction of cognitive impairment in patients with diffuse axonal injury: evidence from a resting-state functional connectivity study.

OBJECTIVE: Diffuse axonal injury (DAI) is a common pathological process after traumatic brain injury, which may cause survivors severe functional disorders, including cognitive impairment and physical disability. Recent literature indicated lateral hypothalamus and medial hypothalamus damage during DAI. Thus, we aim to investigate whether there is imaging evidence of hypothalamic injury in patients with DAI and its clinical association. METHODS: Twenty-four patients with diagnosed DAI and 26 age and sex-matched healthy controls underwent resting-state functional MRI. We assessed the lateral hypothalamus and medial hypothalamus functional connectivity with seed-based analysis in DAI. Furthermore, a partial correlation was used to measure its clinical association. The prediction of the severity of DAI from the altered lateral hypothalamus and medial hypothalamus connectivity was conducted using a general linear model. RESULTS: Compared with healthy control, the DAI group showed significantly decreased lateral hypothalamus functional connectivity with the basal ganglia and cingulate gyrus, which was positively correlated with mini-mental state examination scores (Bonferroni correction at P < 0.0125). Importantly, this disrupted functional connectivity can be used to predict the patients' cognitive state reliably (P = 0.006; P = 0.009, respectively) in DAI. Moreover, we also observed increased connectivity of medial hypothalamus with the superior temporal gyrus and the regions around the operculum. Furthermore, there was a trend of negative correlation between the medial hypothalamus functional connectivity changes to the right superior temporal gyrus and the disability rating scale scores in the DAI group. CONCLUSION: Our results suggest that there are alterations of medial hypothalamus and lateral hypothalamus connectivity in DAI and further understand its clinical symptoms, including related cognitive impairment.

Beneficial effects of a multidomain cognitive rehabilitation program for traumatic brain injury-associated diffuse axonal injury: a case report.

BACKGROUND: Neuropsychological rehabilitation is a crucial component of medical care for patients with diffuse axonal injury (DAI). However, current cognitive intervention programs directed to favor the training of specific domains individually have shown controversial results. Here, we evaluated the effectiveness of a neuropsychological rehabilitation program directed to favor training of attention, memory, visuospatial abilities, and executive functioning together in a patient with severe traumatic brain injury (TBI)-associated DAI. CASE PRESENTATION: A 26-year-old Hispanic woman with a recent history of a severe TBI attended our center complaining of memory problems, dysarthria, and difficulty in planning. A comprehensive cognitive assessment revealed dysfunction in sustained, selective, and divided attention, alterations in memory, planning, and organization of executive behavior, as well as impairment of visuospatial cognitive functions. The patient underwent a 24-week neuropsychological rehabilitation program directed to favor attention, memory, visuospatial abilities, and executive functioning together. After the cognitive intervention, we observed a better patient's performance in tasks requiring sustained, selective, and divided attention, improvement of encoding and retrieval memory problems, use of spatial relationships, planning, and organization of behavior skills. We also observed generalization effects on other domains, such as learning, mental flexibility, inhibition functions, and language. CONCLUSIONS: In conclusion, our results suggest that neuropsychological rehabilitation programs favoring multiple domains together are useful in reestablishing cognitive deficits in patients with severe DAI.

Disrupted hypothalamic functional connectivity related to cognitive impairment after diffuse axonal injury.

ABSTRACT: This study aims to investigate whether there is imaging evidence of disrupted hypothalamic functional connectivity (FC) in patients with diffuse axonal injury (DAI) and relationships with cognitive impairment.Resting-state functional magnetic resonance imaging (fMRI) data were acquired from acute patients with diagnosed DAI (n = 30) and healthy controls (HC) (n = 30). We first assessed hypothalamic FC with seed-based analysis. Furthermore, the lateral and medial hypothalamic seed was selected to show distinct functional connectivity in DAI. In addition, partial correlation was used to measure the clinical associations with the altered hypothalamic FC in DAI patients.Compared with HC, DAI group showed significantly increased hypothalamic FC with superior temporal gyrus, and the regions around the operculum. Furthermore, there was a significant negative correlation between the connectivity coefficient of hypothalamus to right and left superior temporal gyrus and the disability rating scale scores in DAI group. When the seed regions were divided into lateral and medial hypothalamus, except for increased connectivity of medial hypothalamus (P < .01 with correction), we more observed that decreased left lateral hypothalamic connectivity was positively correlated with mini-mental state examination (MMSE) scores.Our results suggest that there are alterations of hypothalamic FC in DAI and offer further understanding of clinical symptoms including related cognitive impairment.

Cognitive-Linguistic outcome in moderate to severe diffuse axonal injury and association with fatigue.

PURPOSE: Individuals with traumatic brain injury (TBI) often have persistent cognitive-linguistic deficits that negatively influence their life. Our objective was to examine the cognitive-linguistic outcome in individuals with moderate to severe diffuse axonal injury (DAI) with a novel test battery. As fatigue is a common symptom affecting the lives of individuals with DAI, we also wanted to assess whether the self-reported fatigue was associated with cognitive-linguistic abilities. METHODS: Selected cognitive-linguistic subtests of the Finnish KAT test and The Mental Fatigue Scale (MFS) were applied to 48 adults with moderate to severe DAI and 27 healthy controls. The majority of the participants with DAI were in the chronic stage. The groups were compared using ANCOVA. Linear regressions were used to analyze the association between MFS and cognitive-linguistic outcomes. RESULTS: The participants with DAI had significantly poorer scores than the controls in most cognitive-linguistic variables and reported significantly more fatigue. Two of the four cognitive-linguistic composite variables were associated with the degree of self-reported fatigue. CONCLUSIONS: Cognitive-linguistic deficits are common in individuals with moderate to severe DAI, and The Finnish KAT test is a valuable tool to detect those. Fatigue was associated with linguistic working memory and language production.

Subcallosal haemorrhage as a sign of diffuse axonal injury in patients with traumatic brain injury.

AIM: To identify the relationship between subcallosal haemorrhage and diffuse axonal injury (DAI) grading. MATERIALS AND METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) images of all patients with traumatic brain injury over the past 5 years were reviewed. Subcallosal haemorrhage was defined as the presence of haemorrhage on admission CT underneath the corpus callosum. Grading of DAI was performed using MRI or CT exclusive of subcallosal haemorrhage status. The association of demographic factors, mechanism of injury, Glasgow Coma Scale (GCS) on admission, and positive subcallosal haemorrhage status with the presence of moderate-severe DAI was assessed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of subcallosal haemorrhage status in predicting DAI severity. Median modified Rankin Scale (mRS) scores were compared between subcallosal haemorrhage positive and negative cases. RESULTS: The images of 1,150 patients were reviewed with 301 patients showing DAI. Of those, 64 patients (21.2%) and 237 patients (78.7%) were positive and negative for subcallosal haemorrhage, respectively. Isolated subcallosal haemorrhage was noted in 15 patients (23.4%). A subcallosal haemorrhage positive status (OR=5.16, p < 0.001) was statistically significantly associated with moderate-severe DAI. The ROC curve for predicting moderate-severe DAI with subcallosal haemorrhage status showed an area under the curve of 0.625 (95% confidence interval [CI]: 0.561-0.688, p < 0.001). The median mRS score was significantly higher (p < 0.001) in the subcallosal haemorrhage positive group (median 4.5, interquartile range [IQR] 2-6) versus the negative group (median 2, IQR 2-3). Isolated subcallosal haemorrhage group showed moderate-severe DAI in 80% (12/15) of cases. CONCLUSION: Subcallosal haemorrhage is a highly specific radiographic predictor of moderate-severe DAI (grade 2-3).

Cognitive Assessment in Patients with Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health problem inWestern countries. ATBI brings many negative consequences, including behavioral and cognitive changes, which affect social adjustment and the performance of functional activities. Cognitive evaluation after TBI is a complex issue in what pertains to definition of the most appropriate questionnaires for clinical use in a comprehensive analysis of the condition of the patient. In this paper, we described a critical review of the main cognitive assessment tests currently used in clinical and research settings in patients with TBI.

MCC950 Inhibits NLRP3 Inflammasome and Alleviates Axonal Injures in Early Stages of Diffuse Axonal Injury in Rats.

Increasing evidence has revealed that neuroinflammation plays a pivotal role in axonal injures. Nucleotide oligomerization domain (NOD)-like receptor protein (NLRP3) inflammasome is reported to be widely involved with the pathology of central nervous system disorders. But the role of NLRP3 in diffuse axonal injury (DAI) are rarely reported. The purpose of this study was to investigate the expression of NLRP3 after diffuse axonal injury and the role of NLRP3 in axonal injures. The lateral head rotation device was used to establish DAI model of rats. Immunohistochemical staining for ß-amyloid precursor protein and Bielschowsky silver staining were used to assess axonal injures and axonal loss. Terminal Deoxynucleotidyl Transferase-Mediated Digoxigenin-dUTP-Biotin Nick-End Labelling Assay was used to detect cell apoptosis. Brain water content was used to assess cerebral edema and the modified Neurologic Severity Score was used to assess the neurological deficits. Components of NLRP3 inflammasome, such as NLRP3, apoptosis-associated speck-like (ASC) adapter protein and caspase-1, and pro-inflammatory cytokines, for example IL-18 and IL-1ß, were over-expressed in early stages of DAI. MCC950, a selective small-molecule inhibitor of NLRP3 inflammasome, inhibited the over-expression of NLRP3 inflammasome and pro-inflammatory cytokines after DAI. MCC950 alleviated axonal injures and cell apoptosis. MCC950 also decreased brain water content and alleviated neurologic deficits 1 day and 3 days after DAI but not 7 days after DAI. These results suggest that MCC950 treatment in the early stages of DAI has a time limiting effect in preventing from axonal injuries and neurological deficits, and that NLRP3 inflammasome plays an important role in axonal injures and may be a potential candidate for axonal injures following DAI.

Behavioral Changes and Associated Factors After Diffuse Axonal Injury.

Diffuse axonal injury (DAI) is a frequent injury after traumatic brain injury (TBI), which causes cognitive and behavioral symptoms. Behavioral changes after DAI affect the patients' quality of life, in addition to causing great damage to their family and society. This study aimed to analyze the behavioral changes of patients with DAI according to family members and to identify the associated factors. This study included patients with DAI, aged between 18 and 60 years, who presented to a referral hospital for traumatic injuries. A prospective cohort study was conducted with 2 evaluations of family members at 3, 6, and 12 months posttrauma. Behavioral changes were evaluated using a questionnaire designed to identify changes according to the perception of family members. The mixed-effects model was applied to identify significant behavioral changes, the effect of time on these changes, and the association between sociodemographic variables, DAI severity, and behavioral changes. Anxiety, dependency, depression, irritability, memory, and mood swings were significantly different (p ≤ .05) before and after trauma. An analysis of the evolution of these behaviors showed that the changes persisted with the same intensity up to 12 months posttrauma. There was an association between depression and income, age and irritability, and DAI severity and dependency. Unfavorable behavioral changes were frequent consequences of DAI, and no improvement in these changes was noted up to 12 months after the injury. Income, age, and DAI severity were related to behavioral changes.

Effect of α7nAChR on learning and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

Permanent isolated micrographia from traumatic basal ganglia injury.

Micrographia is a rare neurological finding in isolation. Most cases of isolated micrographia have been found in association with focal ischemia of the left basal ganglia. Here, we present a case of post-traumatic micrographia stemming from contusion to the left basal ganglia.

Myelin water imaging of moderate to severe diffuse traumatic brain injury.

Traumatic axonal injury (TAI), a signature injury of traumatic brain injury (TBI), is increasingly known to involve myelin damage. The objective of this study was to demonstrate the clinical relevance of myelin water imaging (MWI) by first quantifying changes in myelin water after TAI and then correlating those changes with measures of injury severity and neurocognitive performance. Scanning was performed at 3 months post-injury in 22 adults with moderate to severe diffuse TBI and 30 demographically matched healthy controls using direct visualization of short transverse component (ViSTa) MWI. Fractional anisotropy (FA) and radial diffusivity (RD) were also obtained using diffusion tensor imaging. Duration of post-traumatic amnesia (PTA) and cognitive processing speed measured by the Processing Speed Index (PSI) from Wechsler Adult Intelligence Scale-IV, were assessed. A between-group comparison using Tract-Based Spatial Statistics revealed that there was a widespread reduction of apparent myelin water fraction (aMWF) in TBI, consistent with neuropathology involving TAI. The group difference map of aMWF yielded topography that was different from FA and RD. Importantly, aMWF demonstrated significant associations with PTA (r = -0.564, p = .006) and PSI (r = 0.452, p = .035). In conclusion, reduced myelin water, quantified by ViSTa MWI, is prevalent in moderate-to-severe diffuse TBI and could serve as a potential biomarker for injury severity and prediction of clinical outcomes.

Case of a Hypertensive Crisis in Diffuse Axonal Injury.

This case considers underdosing of analgesics as a prime contributor to hypertension in diffuse axonal injury (DAI) patients who are being mechanically ventilated. In the air medical environment, obtunded patients' hemodynamic parameters are the primary tools available in diagnosing complex disorders such as an acute rise in intracranial pressure (ICP) when invasive ICP monitoring is not available. Therefore, differential diagnoses must follow a continuum, from most severe to least, in order to deal with sudden-onset hypertension rapidly. Not until all critical differentials have been eliminated is analgesia considered. Mimicking the signs of ICP, a compensatory rise in the mean arterial pressure (MAP) is displayed in an acute pain response for mechanically ventilated patients. Therefore, poor analgesic coverage should be considered early in DAI patients who are being ventilated, especially when an increased metabolic drive may be occurring, forcing the therapeutic dosing intervals to be increased. This patient was transferred from Europe back to North America via a fixed wing aircraft, a 16-hour transport time.