Impact of posttraumatic stress disorder and injury severity on recovery in children with traumatic brain injury

The adverse impact on recovery of posttraumatic stress disorder (PTSD) in mild traumatic brain injury (TBI) has been demonstrated in returned veterans. The study assessed this effect in children's health outcomes following TBI and extended previous work by including a full range of TBI severity, and improved assessment of PTSD within a longitudinal design. There were 205 children and adolescents (6 to 15 years of age) who experienced a TBI that were assessed at 2, 3, 6, 12, and 18 months following the TBI. Severity of TBI was classified as mild, moderate, or severe. After controlling for the impact of the severity of TBI, premorbid behavioral and emotional problems and executive function, children with TBI and PTSD did not experience as much psychosocial recovery as those without PTSD. Furthermore the level of psychosocial function was no better than that experienced by children with a severe TBI. In contrast, severe TBI was predictive of a poorer physical recovery in the first 6 months, after which recovery was equivalent across all severity levels.     

Changes in resting connectivity during recovery from severe traumatic brain injury

In the present study we investigate neural network changes after moderate and severe traumatic brain injury (TBI) through the use of resting state functional connectivity (RSFC) methods. Using blood oxygen level dependent functional MRI, we examined RSFC at 3 and 6 months following resolution of posttraumatic amnesia. The goal of this study was to examine how regional off-task connectivity changes during a critical period of recovery from significant neurological disruption. This was achieved by examining regional changes in the intrinsic, or “resting”, BOLD fMRI signal in separate networks: 1) regions linked to goal-directed (or external-state) networks and 2) default mode (or internal-state) networks. Findings here demonstrate significantly increased resting connectivity internal-state networks in the TBI sample during the first 6 months following recovery. The most consistent finding was increased connectivity in both internal and external state networks to the insula and medial temporal regions during recovery. These findings were dissociable from repeat measurements in a matched healthy control sample.     

人脂肪间充质干细胞来源的外排体促进大鼠创伤性脑损伤后神经功能恢复

目的研究人脂肪间充质干细胞(h AMSCs)来源的外排体对创伤性脑损伤(TBI)的治疗作用及其可能的机制。方法分离健康成人脂肪MSCs,通过超滤法提取外排体。将大鼠分成:假手术组,PBS对照组,MSC治疗组,exosomes治疗组。于TBI建模24 h后,治疗组分别沿损伤边缘区局部注射,PBS 30μL,MSC 2×10~5个细胞/只,exosomes 25μg总蛋白量/只,总体积30μL。在建模前和TBI后1、3、7、10、13、16和30 d测试所有大鼠的m NSS评分和前肢踩空试验。3和7d处死大鼠,提取大鼠脑组织总RNA,实时定量PCR检测大鼠炎性因子TNF-α和IL-1β的表达,30 d处死大鼠,tunel-neun双标免疫荧光检测TBI后神经元凋亡。结果外排体的治疗显著促进TBI后的神经功能的恢复,治疗效果与MSC治疗效果相当,其机制可能是通过抑制大鼠TBI后急性炎性反应,减少神经元凋亡。结论人脂肪间充质干细胞来源的外排体促进脑外伤后神经功能的恢复,这将为临床提供一种新的更安全的TBI治疗手段。     

Response inhibition after traumatic brain injury (TBI) in children: impairment and recovery

Children who experience traumatic brain injury (TBI) often show cognitive impairments postinjury, some of which recover over time. We examined the recovery of motor response inhibition immediately following TBI and over 2 years. We assessed the role of injury severity, age at injury, and lesion characteristics on initial impairment and recovery while considering the role of pre-injury psychiatric disorder. Participants were 136 children with TBI aged 5-16 years. Latency of motor response inhibition was measured with the stop-signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. The performance of the TBI participants at each measurement occasion was standardized with 117 children of similar age, but without injury. Residualized latency scores were calculated. Growth curve analyses showed an initial impairment in response inhibition and improvement over the 2 years following injury. Younger TBI patients were initially more impaired although they exhibited greater recovery of response inhibition than did older TBI patients. Longer duration of coma, but not reactivity of pupils or Glasgow Coma Scale score, predicted initial deficit. Lesion characteristics or pre-injury attention deficit hyperactivity disorder did not predict initial impairment or recovery. Replication with longitudinal testing of a comparison group of children sustaining extracranial injury is necessary to confirm our findings.     

Inflicted traumatic brain injury in infants and young children

Abstract This article will discuss the subject of inflicted or abusive head injury in infants and young children. Inflicted neurotrauma is a very common injury and a frequent problem in attempting to distinguish between inflicted and accidental injury. Inflicted head injury occurs usually in the home in the presence of the individual who has inflicted the injury outside the view of unbiased witnesses. Distinguishing between inflicted and accidental injury may be dependent upon the pathological findings and consideration of the circumstances surrounding the injury. The most common finding in an inflicted head injury is the presence of subdural hemorrhage. Subdural hemorrhage may occur in a variety of distributions and appearances. The natural history of subdural bleeding and the anatomy of the "subdural" will be considered. The anatomy of the dura and its attachment to the skull and to the arachnoid determines how subdural bleeding evolves into the cleaved dural border cell layer and as well as how bridging veins are torn and anatomically where bleeding will occur. Different biomechanical mechanisms result in different distributions of subdural blood and these differences will be discussed.     

Changes in working memory after traumatic brain injury in children

The impact of traumatic brain injury (TBI) on working memory (WM) was studied in 144 children (79 with mild, 23 with moderate, and 42 with severe injuries) who underwent magnetic resonance imaging (MRI) at 3 months and were tested at baseline and at 3, 6, 12, and 24 months postinjury. An n-back WM task for letter identity was administered with memory load ranging from 1- to 3-back and a 0-back condition. A TBI Severity x Quadratic Tune interaction showed that net percentage correct (correct detections of targets minus false alarms) was significantly lower in severe than in mild TBI groups. The Left Frontal Lesions x Age interaction approached significance. Mechanisms mediating late decline in WM and the effects of left frontal lesions are discussed.     

Porteus Maze performance following traumatic brain injury in children.

To investigate planning in traumatically brain injured children, the authors gave the Porteus Maze Test (PMT; S. D. Porteus, 1959) to 276 pediatric patients who had sustained a traumatic brain injury (TBI) at least 3 years previously. Sensitivity of the PMT to TBI severity, age at test, and volume of focal brain lesions detected by magnetic resonance imaging was also studied. The Peabody Picture Vocabulary Test-Revised (L. M. Dunn & L. M. Dunn, 1981) was also administered as a control measure. Results indicated that the PMT was highly sensitive to TBI severity and to volume of circumscribed prefrontal lesions. In contrast to the PMT data, receptive vocabulary was related to injury severity but not to discrete prefrontal lesions. Implications for mechanisms of cognitive deficit after TBI in children are discussed.     

Social competence in young children with inflicted traumatic brain injury

As infants develop skills that allow for increasing independence in social and cognitive domains, they acquire the ability to identify goals, sequence behaviors to carry out goals, and to flexibly use strategies for attaining goals in both social and independent play contexts. Little is known about how brain injury in young children may disrupt the precursors to such executive processes. In this study, we examined social and cognitive competence in 25 infants ages 3 to 23 months who sustained moderate to severe traumatic brain injury (TBI) secondary to physical abuse and in 22 healthy community comparison children. Children with TBI were evaluated an average of 1.6 months after the injury. A toy-centered activity with the examiner was used to capture joint attention and social behavior and an exploratory toy play situation was used to measure independent goal-directed play. The inflicted TBI group showed significant reduction in both social and cognitive domains relative to the comparison group. Canonical correlation analyses disclosed that inflicted TBI was associated with reduction in (a) initiation of social interactions, (b) responsiveness to interactions initiated by the examiner, (c) positive affect, and (d) compliance. The groups performed comparably on indexes of gestural and verbal communication and for the occurrence of negative affect. Joint attention was an area of vulnerability for the TBI group in both social initiation and response contexts. Although general cognitive and motor scores were lower in the inflicted TBI group, the complexity of independent toy play did not differ across groups. Early brain injury causes significant disruption in behaviors regulating initiation and responsiveness in social contexts. Longitudinal follow-up will characterize the long-term consequences of early disruption in joint attention and other behaviors on the development of social and cognitive precursors to executive processes.     

成纤维细胞生长因子修饰骨髓间充质干细胞可促进颅脑损伤后功能的恢复

背景：骨髓间充质干细胞虽然能促进神经再生,但因治疗方式局限,并未取得较好的疗效。应用单纯的骨髓间充质干细胞移植治疗脑损伤还远不能达到治疗和改善病情的目的。 目的：探讨成纤维细胞生长因子修饰的骨髓间充质干细胞对颅脑损伤后功能恢复及胶质纤维酸性蛋白表达的影响。 方法：采用液压冲击法建立SD大鼠颅脑创伤模型,建模后随机分为对照组(颅脑损伤组)、骨髓间充质干细胞组及成纤维细胞生长因子-骨髓间充质干细胞组。体外分离、培养骨髓间充质干细胞,利用腺病毒载体介导成纤维细胞生长因子基因转染入骨髓间充质干细胞。采用Western-Blot法检测成纤维细胞生长因子基因转染及胶质纤维酸性蛋白的表达情况;应用免疫组化检测BrdU标记的骨髓间充质干细胞在脑内的分布及数量;利用Longa评分法于移植后1 d、3 d、1周、2周对大鼠进行神经功能学评分;TUNEL法检测脑组织细胞的凋亡情况。 结果与结论：Western-Blot结果显示,成纤维细胞生长因子基因成功转入腺病毒载体,并且能够在骨髓间充质干细胞中表达,且胶质纤维酸性蛋白在成纤维细胞生长因子-骨髓间充质干细胞组的表达明显高于其他两组(P < 0.05)。BrdU标记的骨髓间充质干细胞在成纤维细胞生长因子-骨髓间充质干细胞组脑组织中的表达明显高于其他两组(P < 0.05)。移植后2周,成纤维细胞生长因子-骨髓间充质干细胞组大鼠的神经功能缺损Longa评分明显低于其他两组(P < 0.05)。TUNEL检测到的凋亡细胞数在成纤维细胞生长因子-骨髓间充质干细胞组明显少于其他两组(P < 0.05)。提示成纤维细胞生长因子修饰的骨髓间充质干细胞移植能够减轻颅脑损伤模型大鼠的神经功能损伤程度,促进神经功能恢复,效果优于骨髓间充质干细胞单独移植治疗。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Comprehensive assessment of memory functioning following traumatic brain injury in children

This study examined specific memory functions in 52 children with mild‐moderate or severe traumatic brain injury (TBI) and 29 noninjured controls using the Wide Range Assessment of Memory and Learning (WRAML). Children's recall varied as a function of injury severity and task demands. The participants with severe brain injuries performed worse than controls on global measures of visual memory, learning, and general memory functioning, as well as on specific subtests measuring recall of contextual verbal information. Children with mild‐moderate brain injuries performed similarly to controls except for poorer performance on 2 subtests measuring sound‐symbol learning and recall of geometric designs. Results suggest that the WRAML provides clinically useful information and that specific aspects of memory processing need to be evaluated following childhood TBI.     

Factor structure of the wisc-R in children with traumatic brain injury

The factor structure of the WISC-R was examined in a sample of 108 children with traumatic brain injury. Principal factor analysis of 11 WISC-R subtests yielded three factors, which were subjected to varimax rotation. The rotated factor pattern suggested the existence of a Verbal Comprehension factor, a Perceptual Organization factor, and a somewhat weaker third factor. The meaning and implications of this third factor are discussed.     

Posttraumatic stress symptoms in children following orthopedic or traumatic brain injury

Examined posttraumatic stress (PTS) symptoms in children following pediatric traumatic brain injury (TBI). Children (ages 6-12) with TBI (n = 81) and orthopedic injury (01; n = 59) were assessed 6 and I2 months postinjury. Parents of children with severe TBI reported higher levels of child PTS symptoms than did parents of children with moderate TBI or 0 1 at the 6- and 12-month follow-ups. Group differences in child-reported PTS symptoms emerged at the 12-month follow-up with higher symptom levels reported by children with severe TBI than by those with moderate TBI or OI. At both follow-ups, rates of clinically significant symptom levels were higher in the severe TBI group than in the moderate TBI or OI groups. The group differences in parent and child reports were significant even after taking ethnicity, social disadvantage, and age at injury into account. Parent and child reports of child PTS symptoms were related to family socioeconomic status. Implications for clinical intervention with children and families following pediatric TBI are discussed.     

Chronic administration of antipsychotics impede behavioral recovery after experimental traumatic brain injury

Antipsychotics are often administered to traumatic brain injured (TBI) patients as a means of controlling agitation, albeit the rehabilitative consequences of this intervention are not well known. Hence, the goal of this study was to evaluate the effects of risperidone (RISP) and haloperidol (HAL) on behavioral outcome after experimental TBI. Anesthetized rats received either a cortical impact or sham injury and then were randomly assigned to five TBI (RISP 0.045mg/kg, RISP 0.45mg/kg, RISP 4.5mg/kg, HAL 0.5mg/kg and VEHicle 1mL/kg) and three Sham (RISP 4.5mg/kg, HAL 0.5mg/kg and VEH 1mL/kg) groups. Treatments began 24h after surgery and were provided once daily for 19 days. Behavior was assessed with established motor (beam-balance/walk) and cognitive (spatial learning/memory in a water maze) tasks on post-operative days 1-5 and 14-19, respectively. RISP and HAL delayed motor recovery, impaired the acquisition of spatial learning, and slowed swim speed relative to VEH in both TBI and sham groups. These data indicate that chronic administration of RISP and HAL impede behavioral recovery after TBI and impair performance in uninjured controls.     

Monitoring recovery from traumatic brain injury using automated neuropsychological assessment metrics (ANAM V1.0).

Twenty-two students in the Coastline Community College Traumatic Head Injury Program completed two sessions of neuropsychological testing spaced 2-3 months apart, using ANAM V1.0. Eight (GP1) were marginally injured, seven (GP2) mildly, and seven (GP3) moderately. Comparisons of first-session accuracy scores with normative data revealed that GP1 was impaired on one test, while GPs 2 and 3 were impaired on 3 and 4 tests, respectively. Second-session accuracy scores were normal for GPs 1 and 2 on all tests, and impaired on one for GP3. Comparisons of first-session efficiency scores with normative data indicated that GP1 was significantly impaired on 2 tests, while GPs 2 and 3 were impaired on all 6. Second-session efficiency scores were normal for GP1 on 5 tests; GPs 2 and 3 also improved but remained impaired on all 6 tests. Based on efficiency, 91 % of the individuals were correctly classified.     

Memory functioning following traumatic brain injury in children with premorbid learning problems

This study examines the memory functioning of 25 children who sustained a traumatic brain injury (TBI) and who had prior learning problems, 48 children with TBI who did not have prior learning problems, and 23 noninjured controls. The children with TBI and prior learning problems displayed significantly worse memory abilities than both the control participants and the children with TBI and no prior learning problems. They differed significantly from these 2 groups on measures of general memory, verbal memory, sound-symbol learning, and attention. The results suggest that children with premorbid learning problems who sustain TBI have less cognitive reserve and a lower threshold for the expression of cognitive impairments in areas that reflect preexisting learning and language problems, compared to children without premorbid learning problems.     

Attention deficit hyperactivity disorder in children and adolescents following traumatic brain injury

To better characterize pediatric psychopathology after neurological insult, secondary attention deficit hyperactivity disorder (SADHD)-or ADHD that develops after traumatic brain injury (TBI)-and its clinical and neuroimaging correlates were investigated. Outcome data were available for 118 children, ages 5 through 14 at the time of hospitalization following TBI (severe TBI n = 37; mild-moderate TBI n = 57) and orthopedic injury (n = 24). Standardized psychiatric, adaptive functioning, cognitive functioning, family functioning, and family psychiatric history assessments were conducted on all participants. Severity of injury and neuroimaging lesion assessments were conducted on TBI participants only. The diagnosis of SADHD was mutually exclusive with preinjury ADHD, which occurred in 13 of 94 TBI participants and 4 of 24 orthopedic injury participants. SADHD occurred in 13 of 34 eligible participants with severe TBI but resolved in 4 of 13 of these participants. SADHD also occurred in 1 of 8 eligible moderate TBI participants, only in the presence of preinjury ADHD traits and 3 of 39 of eligible mild TBI cases. SADHD occurred in 1 of 20 of eligible participants with orthopedic injury without any brain injury. SADHD was significantly associated with TBI severity recorded by categorical and dimensional measures, intellectual and adaptive functioning deficits, and personality change due to TBI, but not with lesion area or location. These results suggest that SADHD is a clinically important syndrome after severe TBI in children and adolescents.     

Nitric oxide in traumatic brain injury

Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours-days later. The initial immediate peak in NO after injury is probably due to the activity of endothelial NOS and neuronal NOS. Pre-injury treatment with 7-nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI). After the initial peak in NO, there can be a period of relative deficiency in NO. This period of low NO levels is associated with a low cerebral blood flow (CBF). Administration of L-arginine at this early time improves CBF, and outcome in many models. The late peak in NO after traumatic injury is probably due primarily to the activity of inducible NOS. Inhibition of inducible NOS has neuroprotective effects in most models.