Alterations in Cerebral Oxidative Metabolism following Traumatic Brain Injury

Background  

Traumatic brain injury (TBI) generates regional alterations in cerebral metabolism, leading to the potential evolution of persistent metabolic dysfunction. In the case of penetrating, firearm-related TBI, the pathophysiological mechanisms underlying these acute-phase metabolic derangements are not entirely understood—hindering the potential effectiveness of therapeutic intervention. The use of cerebral microdialysis to monitor biochemical alterations that occur, post-TBI, provides critical insight into the events that perpetuate neurological deterioration.     

Moderate Traumatic Brain Injury: The Grey Zone of Neurotrauma

Moderate traumatic brain injury (MTBI) is poorly defined in the literature and the nomenclature “moderate” is misleading, because up to 15 % of such patients may die. MTBI is a heterogeneous entity that shares many aspects of its pathophysiology and management with severe traumatic brain injury. Many patients who ‘’talk and died’’ are MTBI. The role of neuroimaging is essential for the proper management of these patients. To analyze all aspects of the pathophysiology and management of MTBI, proposing a new way to categorize it considering the clinical picture and neuroimaging findings. We proposed a different approach to the group of patients with Glasgow Coma Scale (GCS) ranging from 9 through 13 and we discuss the rationale for this proposal. Patients with lower GCS scores (9–10), especially those with significant space-occupying lesions on the CT scan, should be managed following the guidelines for severe traumatic brain injury, with ICU observation, frequent serial computed tomography (CT) scanning and ICP monitoring. On the other hand, those with higher range GCS (11–13) can be managed more conservatively with serial neurological examination and CT scans. Given the available evidence, MTBI is an entity that needs reclassification. Large-scale and well-designed studies are urgently needed.     

Effects of a High-Fat Diet on Neuroinflammation and Apoptosis in Acute Stage After Moderate Traumatic Brain Injury in Rats

Neurocritical Care - A high-fat diet (HFD) is correlated with a higher risk of metabolic syndrome. The effect of HFD on neuroinflammation and apoptosis in acute stage after traumatic brain injury...     

Acute Coagulopathy in Isolated Blunt Traumatic Brain Injury

Background  

The role of acute coagulopathy after traumatic brain injury (TBI) on outcome has gained increasing appreciation over the recent years. This study was conducted to assess the frequency, outcome, and risk factors associated with this complication.     

Definite Malingered Neurocognitive Dysfunction in Moderate/Severe Traumatic Brain Injury

There has been disagreement in the literature about whether persons with documented neuropathology can be diagnosed as malingering. To address this question, we present three moderate severe traumatic brain injury patients who were evaluated in the context of litigation who met the Slick, Sherman, and Iverson (1999) criteria for a diagnosis of “Definite Malingered Neurocognitive Dysfunction.” Each performed significantly below-chance on at least one forced-choice symptom validity test, thereby demonstrating a deliberate attempt to appear impaired. These cases represent the first definitive evidence of an intentional effort to appear impaired in the context of documented moderate/severe traumatic brain injury.     

Cognitive Outcome After Mild and Moderate Traumatic Brain Injury in Older Adults

This paper presents findings on the cognitive outcome of older adults sustaining mild traumatic brain injury (TBI). Results indicate that mild TBI patients who are 50 years or older, unlike those with moderate TBI, exhibit cognitive functioning that is comparable to noninjured controls by 1-2-months postinjury. However, these patients continue to report significant anxiety, depression, and somatic preoccupation despite their improvement on objective neuropsychological measures. The lowest postresuscitation Glasgow Coma Scale (GCS) score and the presence of intracranial pathology are more strongly associated with outcome than the durations of posttraumatic amnesia and impaired consciousness, possibly reflecting measurement issues in older persons who are likely to be injured in low velocity falls and to suffer delayed complications. A classification system that considers not only the GCS score but also the presence of intracranial pathology is sensitive to differences in the outcome of older adults, similar to the findings in young patients. The implications of these findings for older TBI patients and directions for research are discussed.     

Alcohol Intoxication as a Stroke Mimic and the Incidence of Acute Alcohol Intoxication in Stroke

Background and AimAlcohol intoxication can be a posterior circulation stroke mimic as they share symptoms such as dysarthria, gait disturbances and nystagmus. We describe alcohol intoxication as a stroke mimic and the frequency of acute alcohol intoxication among stroke patients.MethodsProspective observational single-center study (2014-2017, Haga Ziekenhuis, the Hague). In all patients older than 16 years presenting as possible acute stroke less than 6 hours of onset, blood ethanol was measured; greater than 0.1 blood alcohol concentration (BAC) was considered elevated.ResultsIn total 974 patients were included: 60 (6%) had elevated blood ethanol (mean: 1.3 BAC). In 180 of 974 patients (18%) a stroke mimic was diagnosed: 12 were due to alcohol intoxication (1% of total cohort, 7% of stroke mimic, mean ethanol level: 2.2 BAC). Half of these patients denied or downplayed their alcohol consumption. Stroke and concurrent alcohol intoxication occurred in 38 of 794 strokes (5%, mean ethanol level: 1.1 BAC). Compared to other stroke patients, these 38 patients presented more often after working hours (mean 6.38pm versus 2.23pm) and received alteplase and endovascular therapy less often (24% versus 43%, P = .018 and 3% versus 10%, P = .241, respectively).ConclusionsOf all patients presenting as possible acute stroke, 6% also drank alcohol. 18% of the whole cohort was diagnosed with a stroke mimic. Acute alcohol intoxication as sole diagnosis was diagnosed in 1% of the total cohort and 7% of stroke mimics, 50% denied or downplayed their alcohol consumption. 5% of all stroke patients also drank alcohol, they were significantly less likely to receive alteplase or endovascular treatment.     

Lacosamide Improves Outcome in a Murine Model of Traumatic Brain Injury

Background

Use of antiepileptic drugs (AED’s) is common in the neurocritical care setting. However, there remains a great deal of controversy regarding the optimal agent. Studies associating the prophylactic use of AED’s with poor outcomes are heavily biased by the prevalent use of phenytoin, an agent highly associated with deleterious effects. In the current study, we evaluate lacosamide for neuroprotective properties in a murine model of closed head injury.

Methods

Mice were subjected to moderate closed head injury using a pneumatic impactor, and then treated with either low-dose (6 mg/kg) or high-dose (30 mg/kg) lacosamide or vehicle at 30 min post-injury, and twice daily for 3 days after injury. Motor and cognitive functional assessments were performed following injury using rotarod and Morris Water Maze, respectively. Neuronal injury and microglial activation were measured by flourojade-B, NeuN, and F4/80 staining at 1 and 7 days post-injury. Timm’s staining was also performed to assess lacosamide effects on mossy fiber axonal sprouting. To evaluate possible mechanisms of lacosamide effects on the inflammatory response to injury, an RNA expression array was used to evaluate for alterations in differential gene expression patterns in injured mice following lacosamide or vehicle treatments.

Results

High-dose lacosamide was associated with improved functional outcome on both the rotarod and Morris Water Maze. High-dose lacosamide was also associated with a reduction of neuronal injury at 24 h post-injury. However, the reduction in neuronal loss observed early did not result in greater neuronal density at 31 days post-injury based on unbiased stereology of NeuN staining. High-dose lacosamide was also associated with a significant reduction in microglial activation at 7 days post-injury. The therapeutic effects of lacosamide are associated with a delay in injury-related changes in RNA expression of a subset of inflammatory mediator genes typically seen at 24 h post-injury.

Conclusions

Administration of lacosamide improves functional performance, and reduces histological evidence of acute neuronal injury and neuroinflammation in a murine model of closed head injury. Lacosamide effects appear to be mediated via a reduction or delay in the acute inflammatory response to injury. Prior clinical and animal studies have found antiepileptic treatment following injury to be detrimental, though these studies are biased by the common use of older medications such as phenytoin. Our current results as well as prior work on levetiracetam suggest the newer AED’s may be beneficial in the setting of acute brain injury.     

Alterations in Fibroblast Growth Factor Receptor Expression Following Brain Injury

Traumatic injuries to the central nervous system result in astrogliosis and the formation of a dense scar at the site of the wound. Basic fibroblast growth factor (bFGF) has mitogenic and morphogenic effects on astrocytes, and an interaction between bFGF and its receptor is likely to play a role in astrogliosis. We examined trauma-induced changes in the spatial and temporal expression of FGF receptor (FGFR) in adult rats over a 28-day period following a stereotaxic lesion through the cortex and hippocampus. Immunohistochemistry and image analysis were used to evaluate the changes. Antibody characterization studies strongly suggested that staining represented FGFR 1, but did not rule out possible cross-reactivity with FGFR 2 or 3. Double immunohistochemistry for FGFR and glial fibrillary acidic protein demonstrated that mature astrocytes expressed FGFR. Expression was increased on astrocytes adjacent to the wound cavity by Day 2 postlesion. Staining increased further through Day 10 and decreased to control values by Day 28, except for a sustained increase in staining of reactive astrocytes immediately adjacent to the wound cavity. Basic FGF was detected in the nuclei of cells staining for FGFR, suggesting that FGFR-expressing astrocytes also contained bFGF. These data demonstrate a time course for astrocyte expression of FGFR that precedes and parallels the time course for astrocyte hypertrophy. Our observations suggest that endogenous bFGF, acting directly on FGFR-expressing astrocytes, may contribute to astrogliosis.     

马来酸桂哌齐特对急性中重型颅脑损伤患者的疗效观察

目的 探讨马来酸桂哌齐特对急性中重型颅脑损伤患者的治疗作用。方法 将40例急性颅脑损伤患者随机分为马来酸桂哌齐治疗组(治疗组)和胞二磷胆碱治疗组(对照组),每组20例。所有患者药物治疗均在颅脑损伤后12小时内,在脱水、抗炎、神经营养等常规治疗基础上,治疗组加用马来酸桂哌齐特静脉滴注320mg/d,连续14天为1个疗程。对照组则加用胞二磷胆碱静脉滴注0.75g/d。根据意识觉醒时间、GCS评分、GOS评分以及TCD等,比较两组患者病情恢复情况。结果 急性中重型颅脑损伤治疗中,治疗组在意识觉醒时间上与对照组相比具有明显统计学意义(P<0.05);在不同时期GCS评分上,治疗组与对照组相比也具有明显统计学差异(P<0.05);GOS评分治疗组预后明显优于对照组,具有非常明显的统计学意义(P<0.01);TCD结果显示治疗组缓解脑血管痉挛效果优于对照组。结论 急性颅脑损伤早期应用马来酸桂哌齐特,可降低颅脑外伤后的病残程度,提高治疗效果。     

Hemispheric Differences in Cerebral Autoregulation in Children with Moderate and Severe Traumatic Brain Injury

Introduction  To examine hemispheric differences in cerebral autoregulation in children with traumatic brain injury (TBI). After IRB approval and consent, subjects underwent static cerebral autoregulation testing during the first 9 days after PICU admission. Cerebral autoregulation was quantified using the autoregulatory index (ARI). Results  Forty-two (27 M:15 F) children (10 ± 5 years) with TBI and admission Glasgow coma scale score (5 ± 2) were enrolled. Seven (54%) of the 13 children with focal TBI and 8 (28%) of 29 children with diffuse TBI had impairment or absence of cerebral autoregulation of atleast one hemisphere. In patients with isolated focal TBI, ARI was lower (0.40 ± 0.40 vs. 0.67 ± 0.40; P = 0.03) in the side of TBI than in the unaffected hemisphere, but cerebral autoregulation was often impaired on the side without TBI or shift (5/13) on head CT. There was no difference in ARI between hemispheres in children with diffuse TBI, with or without superimposed focal lesions (P = 0.17). Patients with bilateral intact cerebral autoregulation tended to have higher 6 month Glasgow Outcome Score (GOS) than patients with either unilateral or bilateral cerebral autoregulation impairment (GOS 4.0 ± 0.60 vs. 3.6 ± 0.80; P = 0.08). Conclusions  Hemispheric differences in cerebral autoregulation were common in children with isolated focal TBI. Absence of TBI on CT was not always associated with intact cerebral autoregulation. Patients with bilaterally intact cerebral autoregulation tended to have better outcomes.     

Traumatic Brain Injury: An Objective Model of Consent

The aim of this paper was to explore the issue of consent when considering the use of a life saving but not necessarily restorative surgical intervention for severe traumatic brain injury. A previous study has investigated the issue amongst 500 healthcare workers by using a two-part structured interview to assess opinion regarding decompressive craniectomy for three patients with varying injury severity. A visual analogue scale was used to assess the strengths of their opinions both before and after being shown objective outcome data. Opinions were assessed in a number of scenarios, one of which was that the participants themselves were the injured party. The implication, which was clearly stated, was whether they would provide consent for the procedure to be performed. The study demonstrated that participants were relatively risk aversive in regards to survival with severe disability especially when the injury was severe and there was high probability of that outcome occurring. This finding was not however universal and a minority of participants would provide consent even when the possibility of survival with severe disability was very high. The obvious difficulty comes when considering consent in patients who are unable to express their wishes. In order to address this issue we propose a model of consent based on a balance of the various factors that seem to be of material relevance. These include the severity of the injury, the willingness or otherwise to accept survival with severe disability and the willingness to “risk” the possibility of an unacceptable outcome in order to achieve an acceptable outcome.     

Automated Detection and Quantification of Brain Lesions in Acute Traumatic Brain Injury Using MRI

The purpose of this study is to develop a reproducible method for quantifying brain lesions in traumatic brain injury (TBI). Quantifying the effects of neuropathology is an important goal in the study of brain injury and disease, yet examiners have encountered significant difficulty quantifying brain lesions in neurotrauma where there may exist multiple, overlapping forms of injury including large focal lesions and more subtle, diffuse hemorrhage and/or shear injury. In the current study, we used conventional MRI to quantify brain lesion volume at separate time points in individuals with severe TBI. We present an automated method (ISODATA) for quantifying brain lesions that is compared against a standard semi-automated volumetric approach. The ISODATA method makes no assumptions about the location or extent of brain lesions, instead identifying areas of neuropathology via voxelwise comparisons of MRI signal intensity. The data reveal that ISODATA overlaps significantly with a semi-automated approach, is reliable across multiple observations, and is sensitive to change in lesion size during recovery from TBI. This study validates a reproducible, automated lesion quantification method used here to determine the location and extent of brain pathology following TBI. This approach may be used in conjunction with advanced imaging techniques to characterize the relationship between brain lesions and neurometabolism and function.     

一种改良的创伤性脑损伤模型的建立

目的建立不同损伤程度的创伤性脑损伤模型。方法利用Weiss Young改良的重物打击装置，对36只Wistar大鼠右侧大脑分别给予20g·cm、50g·cm和100g·cm的打击强度致伤。观察大鼠在损伤后不同时间的全身反应、皮层和海马组织的病理学变化及大鼠行为学改变。结果20g·cm打击组大鼠全身反应无异常，皮质轻微挫伤，大鼠逃避反应与伤前无显著差异（P〉0．05）；50g·cm打击组大鼠全身反应轻度异常，皮质挫裂伤，而海马结构基本正常，大鼠逃避反应潜伏期延长（P〈0．05）；100g·cm打击组大鼠全身反应严重异常，皮质及海马均发生明显挫裂伤，大鼠逃避反应潜伏期明显长于前两组（P〈0．05）。结论利用Weiss Young改良的重物打击装置，采用20g·cm、50g·cm和100g·cm的打击强度可较好地制备轻度、中度和重度脑创伤模型。     

Comprehensive Clinical Picture of Patients with Complicated vs Uncomplicated Mild Traumatic Brain Injury

To compare the acute clinical profile of patients with uncomplicated vs complicated mild TBI (MTBI), socio-demographic and medical history variables were gathered for 176 patients diagnosed with MTBI and with (complicated, N = 45) or without (uncomplicated, N = 131) positive findings on cerebral imaging. Neurological examination, neuropsychological assessment and self-evaluation of post-concussive symptoms were done at 2 weeks post trauma. Patients with complicated MTBI were more likely to show auditory and vestibular system dysfunction. Surprisingly, the uncomplicated group reported more severe post-concussive symptoms than patients with positive CT scans. The groups showed no other difference in neurological, psychological, or cognitive outcome. A complete neurological examination should be done acutely in patients with MTBI to determine more specific follow-up required.     

Acute Kidney Injury in Patients with Severe Traumatic Brain Injury: Implementation of the Acute Kidney Injury Network Stage System

Background  

There is limited information on the incidence and effect of acute kidney injury (AKI) in patients with severe traumatic brain injury (TBI), although AKI may affect outcome. Recently, acute kidney injury network (AKIN) classification has been widely accepted as a consensus definition for AKI. The aim of this study is to estimate the frequency and level of severity of AKI in patients with severe TBI by using AKIN criteria and to study whether AKI affects outcome.