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INTRODUCTION: Severe diquat poisoning often leads to acute kidney injury, gastrointestinal injury, paralytic ileus, rhabdomyolysis, respiratory failure, refractory circulatory failure, and brainstem damage. CASE SUMMARY: A previously healthy 38-year-old man was admitted to our hospital with anuria, mild abdominal distension, and calf pain after ingesting diquat (200 g/L) 100 mL approximately 13 h before presentation. His blood diquat concentration was 8.14 µg/L on admission. Gastrointestinal catharsis, haemoperfusion, and haemodiafiltration were performed. Subsequently, he developed marked abdominal distention, impaired consciousness, hypotension, and respiratory failure, leading to death. IMAGES: Computed tomography revealed gas accumulation in the portal venous system and mesenteric vessels. Moreover, gastrointestinal pneumatosis was present. Computed tomography also revealed changes in the lung, brainstem, and calf muscles. CONCLUSION: Diquat poisoning can result in acute kidney injury, hepatic injury, gastrointestinal injury, paralytic ileus, rhabdomyolysis, refractory circulatory failure, brainstem damage, and hepatic portal venous gas, all observed in this patient.

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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 ß-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 ß-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.

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Cavernomas are common, benign vascular lesions that affect the brain. Five-year bleeding risk is approximately 3.8% for asymptomatic lesions. Non-spontaneous, traumatic cavernoma haemorrhage has been seldom reported. We present the case of a 49-year-old male with multiple traumatic brain injuries who was managed conservatively. Initial imaging was suggested, and reported as, a traumatic brainstem haemorrhage. However, after resuscitation and a follow-up MRI scan, the diagnosis of a cavernoma bleed was confirmed in keeping with his mild neurological syndrome. This case illustrates the old dictum to treat the patient and not the scan. It serves as one of the few reported cases of post-traumatic cavernoma bleed, and showcases the difficulty in ascribing haemorrhage to spontaneous or traumatic aetiology. We recommend having a low threshold to investigate further in these unusual situations.

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Background: Traumatic brainstem injury (TBSI) is one of the forms of brain injury and has a very high mortality rate. Understanding the molecular mechanism of injury can provide additional information for clinical treatment. Materials and methods: In this study, we detected transcriptome, proteomics, and metabolome expression changes in the brainstem of TBSI rats, and comprehensively analyzed the underlying mechanisms of TBSI. Results: After TBSI, there was significant diffuse axonal injury (DAI) in the brainstem of rats. A total of 579 genes, 70 proteins, and 183 metabolites showed significant changes in brainstem tissue. Through molecular function and pathway analysis, the differentially expressed genes, proteins, and metabolites of TBSI were mainly attributed to neural signal regulation, inflammation, neuroprotection, and immune system. In addition, a comprehensive analysis of transcripts, proteins, and metabolites showed that the genes, proteins, and metabolic pathways regulated in the brainstem after TBSI were involved in neuroactive ligand-receptor interaction. A variety of GCPR-regulated pathways were affected, especially GAGA's corresponding receptors GABAA, GABAB, GABAC, and transporter GAT that were inhibited to varying degrees. Conclusion: This study provides insights into the development of a rapid diagnostic kit and making treatment strategies for TBSI.

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BACKGROUND: Brainstem toxicity after radiation therapy (RT) is a devastating complication and a particular concern with proton radiation (PBT). We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with PBT. METHODS: All patients <21 years with brain tumors treated with PBT at our institution from 2007-2019, with a brainstem Dmean >30 Gy and/or Dmax >50.4 Gy were included. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, and/or motor weakness with corresponding radiographic abnormality within brainstem. RESULTS: A total of 595 patients were reviewed and 468 (medulloblastoma = 200, gliomas = 114, ependymoma = 87, ATRT = 43) met our inclusion criteria. Median age at RT was 6.3 years and median prescribed RT dose was 54Gy [RBE]. Fifteen patients (3.2%) developed SBI, at a median of 4 months after RT. Grades 2, 3, 4, and 5 brainstem injuries were seen in 7, 5, 1, and 2 patients respectively. Asymptomatic radiographic changes were seen in 51 patients (10.9%). SBI was significantly higher in patients with age ≤3 years, female gender, ATRT histology, patients receiving high-dose chemotherapy with stem cell rescue, and those not receiving craniospinal irradiation. Patients with SBI had a significantly higher V50-52. In 2014, our institution started using strict brainstem dose constraints (Dmax ≤57 Gy, Dmean ≤52.4 Gy, and V54≤10%). There was a trend towards decrease in SBI from 4.4% (2007-2013) to 1.5% (2014-2019) (P = .089) without affecting survival. CONCLUSION: Our results suggest a low risk of SBI after PBT for pediatric brain tumors, comparable to photon therapy. A lower risk was seen after adopting strict brainstem dose constraints.

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OBJECTIVE: In some cases of incomplete cervical spinal cord injury (iSCI) there is marked paresis and dysfunction of upper-extremity movement but not lower-extremity movement. A continued explanation of such symptoms is a somatotopic organization of corticospinal tract (CST) fibers passing through the decussation at the craniovertebral junction (CVJ) and lateral CST (LCST). In central cord syndrome, it has been suggested that injury to the core of the cervical cord may include selective damage to medially located arm/hand LCST fibers, without compromising laterally located leg fibers. Because such somatotopic organization in the primate CST might contribute to the disproportionate motor deficits after some forms of iSCI, the authors made a systematic investigation of CST organization in the CVJ and LCST using modern neuroanatomical techniques. METHODS: High-resolution anterograde tracers were used in 11 rhesus macaque monkeys to define the course of the corticospinal projection (CSP) through the CVJ and LCST from the arm/hand, shoulder, and leg areas of the primary motor cortex (M1). This approach labels CST fibers of all sizes, large and small, arising in these areas. The CSP from the dorsolateral and ventrolateral premotor cortex and supplementary motor area were also studied. A stereological approach was adapted to quantify labeled fiber distribution in 8 cases. RESULTS: There was no evidence for somatotopic organization of CST fibers passing through the CVJ or contralateral LCST. Fiber labeling from each cortical representation was widespread throughout the CST at the CVJ and LCST and overlapped extensively with fibers from other representations. This study demonstrated no significant difference between medial versus lateral subsectors of the LCST in terms of number of fibers labeled from the M1 arm/hand area. CONCLUSIONS: This investigation firmly rejects the concept of somatotopy among CST fibers passing through the CVJ and LCST, in contrast with the somatotopy in the cortex, corona radiata, and internal capsule. All CST fibers in the CVJ and LCST would thus appear to be equally susceptible to focal or diffuse injury, regardless of their cortical origin. The disproportionate impairment of arm/hand movement after iSCI must therefore be due to other factors, including greater dependence of hand/arm movements on the CST compared with the lower limb. The dispersed and intermingled nature of frontomotor fibers may be important in motor recovery after cervical iSCI.

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BACKGROUND: Traumatic 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. METHODS: Patients 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. RESULTS: Mann-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). CONCLUSIONS: These 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.

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BACKGROUND AND PURPOSE: Brainstem hemorrhage (BSH) is the most devastating subtype of intracerebral hemorrhage (ICH) with the highest mortality ranging from 56 % to 61.2 %. However, there is no effective medical or surgical therapy to improve its outcomes in clinic to date due to lack of understanding of its injury mechanisms. Herein, we explored the brainstem iron overload and injury in a rat model of BSH. METHODS: Neurological scores were examined on day 1, 3, and 7 after modeling, and mortality of the rats was recorded to draft a survival curve. Rats were monitored by MRI using T2 and susceptibility weighted imaging (SWI) before sacrifice for examination of histology and immunofluorescence on day 1, 3, and 7. RESULTS: BSH rats had a high mortality of 56 % and demonstrated the severe neurological deficits mimicking the clinical conditions. SWI showed that the same increasing tendency in change of hypointense area with that in iron deposition by Perls staining from day 1 to 7. Expression of heme oxygenase 1 (HO-1) and generation of reactive oxygen species (ROS) had similar tendency and both peaked on day 3. Neuronal degeneration occurred and stayed elevated from day 1 to 7, while myelin sheath injury was initially observed on day 1 but without significant difference within 7 days. CONCLUSIONS: The time courses of erythrocyte lysis, HO-1 expression, iron deposition and ROS generation are related to each other after BSH. Besides, brainstem injury including neuronal degeneration and myelin damage were observed and discussed.

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Radiotherapy (RT) is an effective method for treating head and neck cancer (HNC). However, RT may cause side effects during and after treatment. Radiation-induced brainstem injury (BSI) is often neglected due to its low incidence and short survival time and because it is indistinguishable from intracranial tumor progression. It is currently believed that the possible mechanism of radiation-induced BSI includes increased expression of vascular endothelial growth factor and damage of vascular endothelial cells, neurons, and glial cells as well as an inflammatory response and oxidative stress. At present, it is still difficult to avoid BSI even with several advanced RT techniques. Intensity-modulated radiotherapy (IMRT) is the most commonly used therapeutic technique in the field of RT. Compared with early conformal therapy, it has greatly reduced the injury to normal tissues. Proton beam radiotherapy (PBT) and heavy ion radiotherapy (HIT) have good dose distribution due to the presence of a Bragg peak, which not only results in better control of the tumor but also minimizes the dose to the surrounding normal tissues. There are many clinical studies on BSI caused by IMRT, PBT, and HIT. In this paper, we review the mechanism, dosimetry, and other aspects of BSI caused by IMRT, PBT, and HIT.Key Points• Enhanced MRI imaging can better detect radiation-induced BSI early.• This article summarized the dose constraints of brainstem toxicity in clinical studies using different techniques including IMRT, PBT, and HIT and recommended better dose constraints pattern to clinicians.• The latest pathological mechanism of radiation-induced BSI and the corresponding advanced treatment methods will be discussed.

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The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans, while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters. In this study, we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences. The severe controlled cortical impact model was produced by an electronic controlled cortical impact device, while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube. Body temperature and mortality were recorded, and neurological deficits were assessed with the modified neurological severity score. Brain edema and blood-brain barrier damage were evaluated by assessing brain water content and Evans blue extravasation. In addition, a cytokine array kit was used to detect inflammatory cytokines. Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining. Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations. More severe motor dysfunction was observed in the severe controlled cortical impact model, while more severe cognitive dysfunction was observed in the severe free weight drop model. Brain edema, inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group. The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage, with higher mortality and lower repeatability compared with the severe controlled cortical impact group. Severe brainstem damage was not found in the severe controlled cortical impact model. These results indicate that the severe controlled cortical impact model is relatively more stable, more reproducible, and shows obvious cerebral pathological changes at an earlier stage. Therefore, the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury, while the severe free weight drop model may be more apt for studies on diffuse axonal injury. All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University, China (approval No. IRB2012-028-02) in February 2012.

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To explore the brainstem injury associated with supratentorial lesions, we conducted analysis of ICP levels and detected ENG parameters by using the cold caloric reflex test and histopathological examinations of the brainstem. Rat model of intracerebral hemorrhage was well-established in the study of supratentorial lesions of varying severities (n=210). Intracerebral pressure monitoring and electronystagmography of the cold caloric reflex test were simultaneously performed in animals. Apoptotic, immunohistochemical, and histopathological changes in different segments of the brainstem were investigated at various time intervals. Electronystagmography parameters were analyzed by cold caloric reflex test. The result showed that the increase of intracerebral pressure was correlated with lesion severity including elevating levels and rostral-caudal progression of neuronal apoptosis, demyelination, N-methyl-D-aspartate cell receptor down-regulation (r=0.815), and histopathological changes. Mutiple discrimination analysis of electronystagmography parameters presented a diagnostic accuracy rate of 79.5% in localizing brainstem injury. In conclusion, our data demonstrated that electronystagmography monitoring along with the cold caloric reflex test performed a favorable effect on the estimation of brainstem injury in ICH rat model, which provided a potential bedside diagnostic tool to assess and predict the progress of supratentorial lesion patient in future.

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Objective To explorer the effectiveness of game-based surface electromyographic biofeedback training (GBsEMGBF) on dysphagic brainstem injury patients.Methods Thirty-six brainstem injury dysphagic patients were randomly and evenly divided into a treatment group and a control group,both of 18,by using a random number table.Both groups were given conventional swallowing rehabilitation including oral sensory and motor training,Mendelsohn swallowing training and balloon dilatation of the cricopharyngeal muscle.The treatment group was additionally provided with GBsEMGBF training.All the treatments were provided 5 times per week for 5 weeks.Both groups were assessed using the functional oral intake scale (FOIS),penetration-aspiration scale (PAS),hyoid anterior movement (HAM),hyoid superior movement (HSM) and upper esophageal sphincter opening (UO) before and after the intervention.Results Before the treatment there were no significant differences between the two groups in all the measurements.After the treatment,there was a significant improvement in the average FOIS,PAS,HAM and HSM scores in both groups,but with significantly greater improvement in the treatment group.Significant improvement was observed in the average UO score after the intervention,but without significant differences between the two groups.Conclusion GBsEMGBF can significantly improve the swallowing function and hyoid motor function in dysphagic patients caused by brainstem injury.

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The vertebral arteries are rarely injured in penetrating neck trauma due to their deep location in the foramen transversarium. These injuries in isolation are not associated with neurological deficits or ischemic changes on radiology as the collaterals are usually sufficient. We report a case of fatal unilateral vertebral artery stab injury leading to bilateral cerebellar and brainstem infarction. The carotid Doppler ruled out the presence of any carotid artery injury. Life-threatening injuries are possible in the presence of hypoplastic contralateral vertebral artery or inadequate flow from the anterior circulation not making up for the deficit. This emphasizes that thorough evaluation and timely management of suspected injuries to even a single vertebral artery should be undertaken.

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OBJECTIVES: Routine transnasal rhinological procedures are widely practiced and are considered as safe, in general. Skull base lesions occur in less than 1% of procedures and typically involve the anterior or middle cranial fossa, while clivus lesions have not been well documented. Here we present a series of three patients with iatrogenic transclival lesions after routine transnasal rhinological procedures. PATIENTS AND METHODS: Three patients with penetrating clivus injuries after routine transnasal rhinological procedures were identified. All patients had undergone transnasal rhinological surgery at other hospitals and two of them were referred for emergency treatment. Patients were managed within an interdisciplinary context. RESULTS: There were two women and one man. Mean age at surgery was 35 years. All operations had been performed under general anaesthesia. In only one instance, perforation of the clivus had been noticed during surgery by the ENT physician, while it went unnoticed in the other two patients. In one patient, no intracranial injury occurred secondary to the clivus fracture, while two patients had extensive brainstem lesions. The first patient survived without deficits, but one patient succumbed to the brainstem injury and the other remained with severe deficits. Risk factors including anatomical variants or distorted morphology were present in all patients. CONCLUSION: Transnasal rhinological procedures can result in penetrating clivus injuries, which may not be noticed during surgery, but which can result in permanent morbidity or mortality. These lesions are obviously very rare and their true incidence remains unknown.

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Objectlve To study the significance of injury and posthumous changes to the axonal in brain stem and provide evidence to the forensic discrimination of brainstem injury. Methods Select the cases that died of the primary brainstem injury or other disease randomly, All cases were divided into control group and experimental group, control group and experimental group that were autopsied at the postmortem interval less than 24h or 48h, or longer than 24h or 48h. The brainstem tissue were cut and stained by silver; Two hundred four samples were observed in microscope and selected 9～10 widest axonal to measure its diameter, then analysis the data. Results There is significant difference in axonal diameter of midbrain and mudella between control group (not including those cases died of cardiovascular diseases) and experiment group (P0.05). Conclusion The axonal swelling of the brainstem is closely related with the traumatic injury, so axonal swelling is a finding useful for identification of traumatic brainstem lesions, but death from cardiovascular diseases should be excluded.

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Objective To study pathological changes of acute brainstem injury and evaluate their significance in forensic postmortem diagnosis of brainstem injury. Method To establish an acute brainstem injury model by using a gravitational force of a free falling weight. 50 rats were divided into two groups, an experimental group (35 rats) and a normal control group (15 rats): Neuron apoptosis and neurofilament (NF) of the brain stem were observed by HE, TUNEL and LSAB methods respectively. Results The brainstem injury model was mimic with that occurred in the forensic pathological practice. HE stain showed congestion, edema, loosening of the blood vascular wall as well as the circle hemorrhage of the brain stem and other part of the brain tissues. TUNEL method showed that the neuron apoptosis increased significantly in the cerebral cortex (P

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To study the significance of the pathological changes of axon and myelin sheath in injured brainstem.The neurofilament and myelin basic protein was demonstrated immunohistochemically,and the pathological changes of axons and myelin sheathes in human brainstem following trauma were observed.In the injured brainstem,irregular swelling and disconnecting axons could be found as early as 0 5h after injury, while pathological changes in myelin sheaths such as tortuous change,partial peeling off from axon and intermittent disappearance could be observed at 19～22h after injury.However,in the normal brainstem,there were no evident changes in axons and myelin sheaths.Pathological changes of axon and myelin sheath in brainstem would occur after trauma,which could be used for postmortem diagnosis of brainstem injury.

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Objective To study GFAP changes of astrocyte and expression of Endothelin-1 in molecular pathology in brainstem injury of human being and explore its forensic medical significance. Method 15 brain specimens of acute brainstem injury and 5 brain specimens of no brainstem injury in different time were selected and their microscopic morphological changes were observed with HE staining, and we study the pathological changes of GFAP of astrocyte and expression of Endothelin-1 in monoclonal antibody im-munohistochemistry SP method. Results The number of GFAP positive cells was increased, the bulk of the cell became bigger and expression of Endothelin-1 could be observed. Conclusion The above pathological changes might be a valuable base used for postmortem diagnosis of acute brainstem injury.