Trauma experiences change the brain even in those without PTSD

Trauma may cause distinct and long-lasting effects even in people who do not develop PTSD (post-traumatic stress disorder), according to research by scientists working at the University of Oxford’s Department of Psychiatry. It is already known that stress affects brain function and may lead to PTSD, but until now the underlying brain networks have proven elusive.


Led by Prof Morten Kringelbach, the Oxford team’s systematic meta-analysis of all brain research on PTSD is published in the journal Neuroscience and Biobehavioural Reviews. The research is part of a larger programme on PTSD in British war veterans run by the Scars of War Foundation based at The Queen’s College, University of Oxford. The foundation uses neuroscience to advance understanding of the effects of war and disaster.

The research team’s initial survey of the scientific literature for all the published studies reporting brain activity in individuals with a diagnosis of PTSD yielded over 2000 records. This number was then reduced using stringent criteria to ensure the highest possible data quality for processing with meta-analytic tools.

The team separated studies by type of control group: -exposed (those who had experienced trauma but did not have a diagnosis of PTSD) and trauma-naïve (those who had not experienced trauma), and compared the individuals with PTSD to both groups. This yielded an insight into how the abnormalities in functional brain activity in PTSD comprise a whole-brain network.

The analysis showed that there were differences between the brain activity of individuals with PTSD and that of the groups of both trauma-exposed and trauma-naïve participants.

This suggests that even in the absence of symptoms, trauma may have an enduring effect on . Critically, the research found that in parts of a region of the brain called the , was different when comparing people with PTSD to the trauma-exposed group.

The findings suggest that the transition to clinical PTSD could be linked with imbalances specifically in the basal ganglia – but linked with imbalances in a larger brain network. This view has been reinforced by new evidence uncovered by the team using whole-brain computational modelling of other neuropsychiatric disorders. This modelling showed that these disorders lead to specific imbalances in specific .

Crucially, the meta-analysis has identified the need to directly compare trauma-exposed and trauma-naïve groups to identify potential biomarkers that could help early diagnosis and potentially novel treatments for PTSD.

Professor Kringelbach said: ‘This research suggests that there may be a spectrum of traumatic effect on the brain, where people who have experienced trauma may not meet the threshold for a diagnosis of PTSD but may have similar changes within the brain. This could make them more susceptible to PTSD if they experience a subsequent trauma.

‘While PTSD is often seen and portrayed as an issue for war veterans, it can affect other groups, including emergency service workers and refugees from conflict or disaster. By understanding how the brain is changed, we may be better placed to prevent the effects of trauma developing into clinical PTSD.’

PTSD often presents as a series of non-specific, confusing and distressing symptoms. The condition is therefore difficult for clinicians to differentiate from a wide variety of others. In particular among soldiers, PTSD can initially seem very similar to the effects of explosions and blows to the head. Mild traumatic brain injury (mTBI) and PTSD are especially common in soldiers and war veterans.

After the end of World War One, the Report of the War Office Committee of Enquiry into “Shell Shock.” announced the need to differentiate between the effects of trauma and brain injury. Resolving this long-outstanding question is an important part of the Scars of War Foundation’s remit.

The new insights are guiding the research team’s brain imaging study of British war veterans, which is about to start and which will compare veterans with PTSD to veterans both with and without trauma. Better understanding of the brains of war veterans is a vital first step in the Foundation’s aim of providing clinicians with the means to make early diagnoses, while increasing the accuracy of early diagnoses has the potential to avoid the progression to intractable chronic versions of these conditions.

That could cut costs for war veteran care. It would also make possible the development of more effective treatments.

The Director of Scars of War Foundation and Falklands War veteran Hugh McManners commented: ‘A possible implication of our research is that because trauma seems to lead to brain changes in everyone who is exposed, PTSD may not actually be abnormal or a ‘disorder’ but the ‘s natural reaction to events and experiences that are abnormal. There may therefore be more ‘natural’ military and social methods of preventing and treating it. We hope to elucidate this further in the scanning phase of this project. More immediately, this could prove significant in helping to remove the stigma suffered by Service men and women who develop PTSD.’

Reducing trauma deaths in the UK.

Traumatic haemorrhage is a leading cause of death in young adults in the UK.1 The CRASH-2 trial showed that the early administration of tranexamic acid safely reduces mortality in bleeding trauma patients.2 Further study demonstrated that the treatment is widely practicable and cost effective.3

RoadPeace—the UK national charity for road crash victims—represented trauma victims on the CRASH-2 trial steering committee, and we are now committed to ensuring that victims benefit from this life-saving treatment. To assess whether bleeding trauma patients in the UK are treated with tranexamic acid, we sent freedom of information requests to 291 UK hospitals in September, 2012, which asked the following questions: does your hospital’s trauma protocol include administration of tranexamic acid to bleeding trauma patients; and in 2011, how many acute trauma patients received a blood transfusion and, of those, how many were treated with tranexamic acid?

209 (72%) of the 291 hospitals responded. Of these 209 hospitals, 11 stated that they did not treat trauma patients and 19 failed to answer the question about trauma protocols. Of the 179 remaining hospitals, 159 (89%) include tranexamic acid in their trauma protocols. The second question aimed to assess whether bleeding trauma patients received tranexamic acid. Most hospitals did not answer this question (citing the pertinent Freedom of Information Act 2000 clause) on the basis that it would be too costly to obtain the data. 34 hospitals reported the number of trauma patients that received a blood transfusion and the number given tranexamic acid. Of 451 trauma patients transfused at these 34 hospitals, 34 (8%) received tranexamic acid. Four of these 34 hospitals were major trauma centres. Of 285 trauma patients transfused at these four major trauma centres, 13 (5%) received tranexamic acid.

Although tranexamic acid is included in most hospital trauma protocols, our data show that few bleeding trauma patients were given this treatment in 2011. Patients with trauma severe enough to require blood transfusion would be expected to benefit from tranexamic acid, and we are concerned that patients were denied this life-saving treatment. One explanation for the low use is that tranexamic acid might not have been incorporated into trauma protocols for the full duration of 2011. Since most hospitals now include tranexamic acid in their trauma protocols, more recent figures might be higher.

We will repeat this survey in 2013 to assess progress. We are optimistic that use will improve because of recent and rapid policy responses—notably, the aforementioned trauma protocol coverage, the Trauma Promise, and the NHS move to include tranexamic acid administration in its 2013—14 best practice tariff for major trauma centres.45 To support these efforts, we recommend that tranexamic acid be included in trauma audit at all UK accident and emergency hospitals and that hospitals regularly publish data on the proportion of trauma patients that are appropriately given the treatment. We urge all UK hospitals to reaffirm their commitment to providing effective trauma care by making the Trauma Promise.

Source: Lancet


The development and validation of an internet-based training package for the management of perineal trauma following childbirth:MaternityPEARLS.


Background Birth-related perineal trauma has a major impact on women’s health. Appropriate management of perineal injuries requires clinical knowledge and skill. At present, there is no agreement as to what constitutes an effective clinical training programme, despite the presence of sufficient evidence to support standardised perineal repair techniques. To address this deficiency, we developed and validated an interactive distance learning multi-professional training package called MaternityPEARLS.

Method MaternityPEARLS was developed as a comprehensive e-learning package in 2010. The main aim of the MaternityPEARLS project was to develop, refine and validate this multi-professional e-learning tool. The effect of MaternityPEARLS in improving clinical skills and knowledge was compared with two other training models; traditional training (lectures + model-based hands on training) and offline computer lab-based training. Midwives and obstetricians were recruited for each training modality from three maternity units. An analysis of covariance was done to assess the effects of clinical profession and years of experience on scoring within each group. Feedback on MaternityPEARLS was also collected from participants. The project started in January 2010 and was completed in December 2010.

Results Thirty-eight participants were included in the study. Pretraining and post-training scores in each group showed considerable improvement in skill scores (p<0.001 in all groups). Mean changes were similar across all three groups for knowledge (3.24 (SD 5.38), 3.00 (SD 3.74), 3.30 (SD 3.73)) and skill (25.34 (SD 8.96), 22.82 (SD 9.24), 20.7 (SD 9.76)) in the traditional, offline computer lab-based and e-learning groups, respectively. There was no evidence of any effect of clinical experience and baseline knowledge on outcomes.

Conclusions MaternityPEARLS is the first validated perineal trauma management e-learning package. It provides a level of improvement in skill and knowledge comparable to traditional methods of training. However, as an e-learning system, it has the advantage of ensuring the delivery of a standardised, continuously updated curriculum that has global accessibility.

Source: PMJ. BMJ


Response to acute concussive injury in soccer players: is gender a modifying factor?

Several studies have suggested a gender difference in response to sports-related concussion (SRC). The Concussion in Sport group did not include gender as a modifying factor in SRC, concluding that the evidence at that point was equivocal. In the present study the authors endeavored to assess acute neurocognitive and symptom responses to an SRC in equivalent cohorts of male and female soccer players. The authors hypothesized that female athletes would experience greater levels of acute symptoms and neurocognitive impairment than males.


Baseline symptom and neurocognitive scores were determined in 40 male and 40 female soccer players by using the Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) scale prior to any SRC. After sustaining an SRC, each athlete completed postconcussion ImPACT tests and was carefully matched on a wide array of biopsychosocial variables. Baseline symptom and neurocognitive test scores were compared, and their acute symptoms and neurocognitive responses to concussive injury were assessed.


Specific a priori hypotheses about differences between males and females at baseline and at postconcussion measurements of verbal and visual memory ImPACT scores were evaluated according to simple main effects of the gender variable and according to baseline-to-postconcussion main effect and interaction of 2 × 2 split-plot ANOVA. Neither the interaction nor the main effects nor the simple main effects for either ImPACT variable were found to be statistically significant. Exploratory ANOVAs applied to the remaining ImPACT variables of visualmotor speed, reaction time, impulse control, and symptom total scores revealed only a single statistically significant baseline-to-postconcussion main effect for the symptom total.


The results failed to replicate prior findings of gender-specific baseline neurocognitive differences in verbal and visual memory. The findings also indicated no differential gender-based acute response to concussion (symptoms or neurocognitive scores) among high school soccer players. The implications of these findings for the inclusion of gender as a modifying factor in this tightly matched cohort are addressed. Potential explanations for the null findings are discussed.

Source: Journal of Neurosurgery

The prognostic significance of traumatic brainstem injury detected on T2-weighted MRI.

Magnetic resonance imaging is frequently used to evaluate patients with traumatic brain injury in the acute and subacute setting, and it can detect injuries to the brainstem, which are often associated with poor outcomes. This study was undertaken to determine which MRI and clinical factors provide prognostic information in patients with traumatic brainstem injuries.


The authors performed a retrospective analysis of cases involving patients admitted to a Level I trauma center who were identified in a prospective database as having suffered traumatic brainstem injury identified on MRI. Patient outcomes were dichotomized to dead/vegetative versus functional groups. Standard demographic data, admission Glasgow Coma Scale (GCS) scores, results of the motor component of the GCS examination at admission and 24 hours later, CT scan findings, and peak intracranial pressure were collected from medical records. Volumetric analysis of each patient’s injuries was performed with T2-weighted and gradient echo sequences. The T2-weighted MRI sequence for each patient was reviewed to determine the anatomical location of injury within the brainstem and whether the injury crossed the midline.


Thirty-six patients who met the study inclusion criteria were identified. At 6-month follow-up, 53% of these patients had poor outcomes and 47% had recovered. Patients with injuries to the medulla or deep bilateral injuries to the pons did not recover. The T2 volumes were found superior to gradient echo sequences in regard to predicting survival (ROC/AUC 0.67, p = 0.07 vs 0.60, p = 0.29, respectively), but neither reached statistical significance. The timing of MR image acquisition did not influence the findings. The time from admission to MRI did not differ significantly between the recovered group and the poor-outcome group (p = 0.52, Mann-Whitney test), and lesion size as measured by T2 volume did not vary with time to scan (R2 = 0.03, p = 0.3, linear regression). Performing a stepwise logistic regression with all the variables yielded the following factors related to recovery: crossing midline, p = 0.0156, OR 0.075; and 24-hour GCS motor score, p = 0.0045, OR = 2.25, c-statistic 0.913. Further examination of these 2 factors disclosed the following: none of 15 patients with midline-crossing lesions and a 24-hour GCS motor score of 4 or less recovered; conversely, 12 of 13 patients with lesions that did not cross midline recovered, regardless of GCS motor score.


Bilateral injury to the pons and medulla as detected on T2-weighted MRI sequences was associated with poor outcome in patients with brainstem injuries; T2 volumes were found superior to gradient echo sequences in regard to predicting survival, but neither reached statistical significance. When MRI findings were coupled with clinical examination findings, a strong correlation existed between poor outcome and the combination of bilateral brainstem injury and a motor GCS score of 4 or less 24 hours after admission.

Source: Journal of Neurosurgery.


Hypertonic saline for treating raised intracranial pressure: literature review with meta-analysis A review.

Currently, mannitol is the recommended first choice for a hyperosmolar agent for use in patients with elevated intracranial pressure (ICP). Some authors have argued that hypertonic saline (HTS) might be a more effective agent; however, there is no consensus as to appropriate indications for use, the best concentration, and the best method of delivery. To answer these questions better, the authors performed a review of the literature regarding the use of HTS for ICP reduction.


A PubMed search was performed to locate all papers pertaining to HTS use. This search was then narrowed to locate only those clinical studies relating to the use of HTS for ICP reduction.


A total of 36 articles were selected for review. Ten were prospective randomized controlled trials (RCTs), 1 was prospective and nonrandomized, 15 were prospective observational trials, and 10 were retrospective trials. The authors did not distinguish between retrospective observational studies and retrospective comparison trials. Prospective studies were considered observational if the effects of a treatment were evaluated over time but not compared with another treatment.


The available data are limited by low patient numbers, limited RCTs, and inconsistent methods between studies. However, a greater part of the data suggest that HTS given as either a bolus or continuous infusion can be more effective than mannitol in reducing episodes of elevated ICP. A meta-analysis of 8 prospective RCTs showed a higher rate of treatment failure or insufficiency with mannitol or normal saline versus HTS.

Source: Journal of Neurosurgery