The purpose of this article is to review relevant literature on the effect of mild traumatic brain injury (mTBI) and blast injury on the vestibular system. Dizziness and imbalance are common sequelae associated with mTBI, and in some individuals, these symptoms may last for six months or longer. In war-related injuries, mTBI is often associated with blast exposure. The causes of dizziness or imbalance following mTBI and blast injuries have been linked to white matter abnormalities, diffuse axonal injury in the brain, and central and peripheral vestibular system damage. There is some evidence that the otolith organs may be more vulnerable to damage from blast exposure or mTBI than the horizontal semicircular canals. In addition, benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder following head injury that is treated effectively with canalith repositioning therapy. Treatment for (non-BPPV) mTBI-related vestibular dysfunction has focused on the use of vestibular rehabilitation (VR) augmented with additional rehabilitation methods and medication. New treatment approaches may be necessary for effective otolith organ pathway recovery in addition to traditional VR for horizontal semicircular canal (vestibulo-ocular reflex) recovery.

Mild traumatic brain injury (mTBI), often referred to as concussion, has become increasingly recognized as a serious health issue in the general population. The prevalence of mTBI in athletes, particularly repeated injuries in young athletes, is of great concern as injuries to the developing brain can have long-term detrimental effects. In this study we used a novel awake closed-head injury (ACHI) model in rodents to examine repeated mTBI (rmTBI), to determine if repeated injuries produced the neurological and molecular changes evident with human concussion. Animals were administered 4, 8, and 16 rmTBIs and acute neurological assessments were performed after the injuries. Changes in glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) levels were assessed using Western blot analysis at one day following rmTBI in the ipsilateral dentate gyrus (DG) and the cornu ammonis (CA) regions of the hippocampus and the cortex (CX) indicative of astrocyte and microglial cell reactivity. Results indicated that the ACHI model produces neurological deficits immediately after the injuries, with the most deficits arising in the rmTBI16 group. Despite deficits in all injury groups, histological staining with cresyl violet revealed no significant morphological tissue damage to the brain. Western blot analysis, however, showed a significant increase in DG and CX GFAP expression in the rmTBI16 group with no changes in Iba-1 levels. This suggests an acute activation of astrocytes in response to injury, with a delay or absence of microglial activation. Our findings show that with repetitive concussions, we are able to detect acute neurological and molecular changes in the juvenile female brain. However, further investigation is necessary to determine if these are transient changes. / Graduate

BACKGROUND:Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury.FINDINGS:Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes.CONCLUSIONS:This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.

Acquired brain injury (ABI) and long-term neurological conditions (such as multiple sclerosis, Parkinson’s disease), are major causes of disability in the UK, and can lead to significant physical, cognitive, neuro-behavioural, psychological and social difficulties for sufferers. Individuals affected by an ABI or neurological conditions commonly report difficulties around emotional adjustment, reduced attention, mental control, and self-efficacy and their health-related quality of life also often appears to be much reduced. Whilst conventional neuro-rehabilitation has tended to address physical and cognitive impairments and deficits rather than psychological sequelae, recently a growing trend for more holistic approaches appears to have emerged (e.g., Wilson et al., 2000, 2013). Amongst these approaches, mindfulness-based interventions (collectively known as MBIs) have sought to address this gap in terms of therapeutic intervention. There is a growing body of research evidence pointing to the utility of MBIs in the rehabilitation and support of these populations in improving perceived quality of life and increasing self-management of these conditions. However, the research still remains limited and debate persists in terms of the conceptual and theoretical framework of mindfulness. The present study sought to evaluate the effectiveness of an adapted, short-form MBI group programme for a mixed population of patients (n = 22) currently offered in a local neuro-rehabilitation service. A specific pre-post control group design was adopted in order to investigate whether the intervention produced improvements in mindfulness skills, and whether these would in turn lead to improvements in measures associated with self-efficacy and perceived quality of life. Results indicated participants completing the MBI group programme showed significantly higher mean scores across measures of mindfulness. The results also indicated that these improvements were predictive of improvements across self-efficacy and quality of life measures, with large effect sizes observed. The findings would appear to support the research hypothesis that a suitably modified MBI is beneficial for a mixed ABI population. Findings, study limitations, clinical relevance and implications, as well as methodological and theoretical considerations and directions for future research are discussed in light of the main research questions.

Reactive oxygen species (ROS) is cytotoxic to the cell and is known to contribute to secondary cell death following primary traumatic brain injury (TBI). We described in our study that PN is the main mediator for both lipid peroxidation and protein nitration, and occurred almost immediately after injury. As a downstream factor to oxidative damage, the peak of Ca2+-dependent, calpainmediated cytoskeletal proteolysis preceded that of neurodegeneration, suggesting that calpain-mediated proteolysis is the common pathway leading to neuronal cell death. The time course study clearly elucidated the interrelationship of these cellular changes following TBI, provided window of opportunity for pharmacological intervention. Furthermore, we conducted a pharmacological study to solidify our hypothesis. First of all, we tested the potency of a membrane permeable, catalytic scavenger of PN-derived free radicals, tempol for its ability to antagonize PN-induced oxidative damage. Tempol successfully inhibited PNinduced protein nitration at dosages of 30, 100 and 300mg/kg. Moreover, early single dose of 300mg/kg was administered and isolated mitochondria were examined for respiratory function and oxidative damage level. Our data showed that tempol reduced mitochondrial oxidative damage, and maintained mitochondrial function within normal limits, which suggested that tempol is efficiently permeable to mitochondrial membrane and mitochondrial oxidative damage is essential to mitochondrial dysfunction. Next, we found that calpainmediated proteolysis is reduced at early treatment with a single dose of tempol. However, the effect of tempol on calpain is short-lived possibly due to systematic elimination. In our multiple dose study, tempol showed a significant inhibitory effect on SBDPs. Consequently, we measured neuordegeneration with the de Olmos aminocupric silver staining method at 7 days post-injury and detected a significant decrease of neuronal cell death. Together, the time course study and pharmacological study strongly support the hypothesis that PN is the upstream mediator in secondary cell death in the CCI TBI mouse model. Moreover, inhibition of PN-mediated oxidative damage with the antioxidant, tempol, is able to attenuate multiple downstream injury mechanisms. However, targeting PN alone may be clinically impractical due to its limited therapeutic window. This limitation may be overcome in future studies by a combination of multiple therapeutic strategies.

Tyrimo tikslas. Palyginti eisenos atsigavimą asmenims, patyrusiems trauminį galvos smegenų sužalojimą (TGSS) ar galvos smegenų infarktą (GSI), pirmajame reabilitacijos etape taikant kineziterapiją. Tyrimo uždaviniai.1) Įvertinti asmenų, patyrusių TGSS ar GSI, protinę būklę ir mobilumą prieš ir po kineziterapijos; 2) Įvertinti asmenų, patyrusių TGSS, eiseną taikant kineziterapiją pirmojo reabilitacijos etapo pradžioje ir pabaigoje; 3) Įvertinti asmenų, patyrusių GSI, eiseną taikant kineziterapiją pirmojo reabilitacijos etapo pradžioje ir pabaigoje; 4) Įvertinti asmenų, patyrusių TGSS ar GSI, proto būklės ir mobilumo atsigavimo įtaką eisenos atsigavimui, taikant kineziterapiją. Tyrimo metodai. Tyrime dalyvavo 60 asmenų: 30 asmenų, patyrusių TGSS, ir 30 asmenų, patyrusių GSI. Visiems tiriamiesiems buvo sutrikusi eisena. Vertinome tiriamųjų proto būklę pagal Trumpą Proto Būklės Tyrimo Testą, (TPBVT), mobilumą pagal Rivermead’o mobilumo indeksą (Rivermead Mobility Index) ir eiseną pagal Dinaminį Eisenos Indeksą (Dynamic Gait Index). Rezultatai skaičiuoti atliekant matematinę statistinę analizę. Visiems tiriamiesiems buvo taikoma kineziterapija siekiant eisenos atsigavimo. Tyrimo rezultatai. Tyrimo rezultatai parodė, kad taikant kineziterapiją pagerėjo proto būklė, mobilumas ir eisena abiejose tiriamųjų grupėse. Atlikus asmenų po TGSS ar GSI proto būklės, mobilumo ir eisenos palyginamąją analizę, gavome, kad kineziterapija turi teigiamą įtaką abiejų grupių proto būklės, mobilumo... [toliau žr. visą tekstą] / The aim. To compare gait recovery of individuals after Traumatic Brain Injury (TBI) or Ischemic Brain Stroke (IBS) using Physical Therapy during first rehabilitation stage. The tasks were: 1) To evaluate individuals after TBI or IBS mental state and mobility before and after Physical Therapy. 2) To evaluate individuals gait after TBI before and after Physical Therapy during first rehabilitation state. 3) To evaluate individuals gait after IBS before and after Physical Therapy during first rehabilitation state. 4) To find correlation between mental state, mobility and gait recovery of individuals after TBI or IBS using Physical Therapy. Methods and Material. In this study there were 60 persons participated: 30 after TBI and 30 after IBS. All patients had gait disorders. We evaluated mental state using Mini Mental State Examine (MMSE), mobility using Rivermead Mobility Index (RMI) and gait using Dynamic Gait Index. The results were calculated using mathematical statistical analysis. All patients received Physical Therapy to improve their gait. Results. The results showed significant mental state, mobility and gait recovery after Physical Therapy in both groups. Comparative analysis of persons after TBI or IBS mental state, mobility and gait showed that Physical Therapy has a statistically significant influence on mental state, mobility and gait recovery in both groups. We found correlation between mental state, mobility and gait recovery for patients after TBI or IBS. Gait... [to full text]

Background: Trauma is a major cause of death and disability. Adverse events, such as prolonged prehospital time, hypoxia, hypotension and/or hyperventilation have been reported to correlate to poor outcome. Adequate cortisol levels are essential for survival after major trauma. In hypotensive critically ill patients, lack of sufficient amount of cortisol can be suspected, and a concept of critical illness related corticosteroid insufficiency has been proposed. Corticosteroid therapy has many adverse effects in critically ill patients and should only be given if life-saving. Correct measurement of serum cortisol levels is important but difficult in critically ill patients with capillary leakage. Estimation of the free and biologically active cortisol is preferable. In serum less than 10% of cortisol is free and biologically active and not possible to measure with routine laboratory methods. Salivary cortisol can be used as a surrogate for free cortisol, but salivary production is reduced in critically ill patients. Liver resection could reduce cortisol levels due to substrate deficiency. Aims: 1. Evaluate the occurrence of early adverse events in patients with traumatic brain injury and relate them to outcome. 2. Assess cortisol levels over time after trauma and correlate to severity of trauma, sedative/analgesic drugs and cardiovascular function. 3. Evaluate if saliva stimulation could be performed without interfering with salivary cortisol levels. 4. Assess cortisol levels over time after liver resection in comparison to other major surgery. Results: There was no significant correlation between prehospital time ³60 minutes, hypoxia (saturation <95%), hypotension (systolic blood pressure <90 mmHg), or hyperventilation (ETCO2 <4.5 kPa) and a poor outcome (Glasgow Outcome Scale 1-3) in patients with traumatic brain injury. Cortisol levels decreased significantly over time after trauma, but there was no correlation between low (<200 nmol/L) serum cortisol levels and severity of trauma. Infusion of sedative/analgesic drugs was the strongest predictor for a low (<200 nmol/L) serum cortisol. The odds ratio for low serum cortisol levels (<200 nmol/L) was 8.0 for patients receiving continuous infusion of sedative/analgesic drugs. There was no significant difference between unstimulated and stimulated salivary cortisol levels (p=0.06) in healthy volunteers. Liver resection was not associated with significantly lower cortisol levels compared to other major surgery. Conclusion: There was no significant correlation between early adverse events and outcome in patients with traumatic brain injury. Cortisol levels decreased significantly over time in trauma patients. Low cortisol levels (<200 nmol/L) were significantly correlated to continuous infusion of sedative/analgesic drugs. Saliva stimulation could be performed without interfering with salivary cortisol levels. Liver resection was not associated with low cortisol levels compared to other major surgery.

People with a diagnosis of schizophrenia have been found to perform poorly on tasks assessing semantic memory, and these impairments have been proposed to be related to certain symptoms, in particular Formal Thought Disorder (FTD). A systematic literature review and meta-analysis identified the need a) to determine whether semantic memory is a primary impairment in schizophrenia and not secondary to other cognitive impairments and b) what cognitive models could provide the best explanation for the impairment. With these aims, Studies One and Two compared the performance of a group of people with schizophrenia across a battery of semantic memory tests (Hodges, Salmon and Butters, 1992). In order to eliminate confounding variables, two clinical control groups were recruited for comparison, one with a probable degraded semantic memory arising from Alzheimer‘s Dementia (AD) and the other with a primary dysexecutive syndrome caused by acquired brain injury (ABI). From these comparisons, it was possible to profile the semantic memory impairment in schizophrenia with the conclusion that any deficits are task-specific. Unlike the AD group, the impairment did not seem to arise from a loss of stored knowledge but nor did a retrieval problem, in its simplest terms, offer the best explanation. Since the ABI group performed normally on the battery it is clear that a dysexecutive syndrome does not necessarily explain poor semantic memory performance. Qualitatively, the associations and categories formed by people with schizophrenia on tasks of semantic categorisation e.g. the Category Generation Test (CGT) (Green, Done, Anthony, McKenna and Ochocki, 2004) often resemble loosening of associations and psychotic speech. In order to understand more about the processes involved in the formation of these bizarre categories, I compared performance on the CGT of groups of people with schizophrenia, AD and ABI. I found that the people with AD performed fairly similarly to the people with schizophrenia in that they sorted cards in an idiosyncratic way but the ABI group performed normally, adhering to taxonomic categories. Although this result might suggest that the bizarre associations on the CGT in people with schizophrenia are caused by a deficit in semantic memory (and not a dysexecutive syndrome), further analysis found important differences between the AD and the schizophrenia group in the way the card sorts were formed. In addition, both these groups showed intact semantic memory knowledge of the items they mis-sorted, indicating that categorisation problems do not necessarily arise from a degraded memory store. The difficulties people with schizophrenia appear to have on tests of associations and categorisation (e.g. CGT) could arise from a disorganised semantic memory i.e. differences in the way in which concepts are interconnected. On the CGT, patients with schizophrenia were far more likely to sort items on the basis of thematic (situational) information suggesting a preference for thematic over taxonomic associations. To test this, participants were tested using a triadic comparison task which requires choosing whether an item is best associated with a taxonomic, thematic or perceptually related item. On this test patients performed comparably to controls suggesting that their semantic memory is organised normally and that the abnormalities in the way in which items are associated on some semantic memory tests, including the CGT, are task-specific. It has been proposed that one of the core problems in schizophrenia is that there is ―an aberrant assignment of salience‖ (Kapur 2003) to contextually inappropriate concepts due to a dysregulated dopamine system (Kapur 2003; Kapur et al 2005). It is possible that this could also explain the semantic memory impairments in schizophrenia i.e. certain less relevant concepts/ associations are chosen because they are experienced as more salient. To test this, a group of patients with schizophrenia were assessed using a test of semantic salience. Compared to controls, the patients made significantly more errors of salience including significantly more errors where large aberrant attributions of importance were given to items. The tendency to make errors on the salience test was highly correlated with errors on the CGT and also the semantic association tests, indicating a common underlying mechanism. Therefore, it can be concluded that the semantic memory impairments in schizophrenia are task-specific, not caused by a loss of semantic knowledge or a dysexecutive syndrome, but due to an aberrant assignment of salience to less relevant semantic concepts. More work is needed to understand the cognitive processes underlying this aberrant attribution process, and also the biological substrates involved.

Résumé : Les réanimateurs ont recours à des interventions à la fois médicales et chirurgicales en contexte de choc traumatique. Le rôle des vasopresseurs dans cette prise en charge est controversé. Alors que les lignes directrices américaines considèrent que les vasopresseurs sont contre-indiqués, certains experts européens en encouragent l’utilisation pour diminuer le recours aux liquides intraveineux. Avant d’élaborer un essai clinique, il importe de comprendre la pratique actuelle à laquelle se comparera une intervention expérimentale, ainsi que de connaître le niveau d’incertitude dans la littérature entourant la question de recherche. Le Chapitre 2 de ce travail présente une étude observationnelle effectuée dans un centre régional de traumatologie québécois. Cette étude documente les pratiques de réanimation adoptées par les équipes de traumatologie en 2013, particulièrement le recours aux liquides intraveineux et aux vasopresseurs. Les résultats démontrent que les vasopresseurs ont été utilisés chez plus de 40% des patients, particulièrement les victimes de traumatismes crâniens (RC 10.2, IC 95% 2.7-38.5). De plus, les vasopresseurs ont été administrés dans les phases précoces de la réanimation, soit avant l’administration d’un volume important de liquides. Le Chapitre 3 présente une revue systématique portant sur l’utilisation précoce de vasopresseurs en traumatologie. Les bases de données MEDLINE, EMBASE, CENTRAL et ClinicalTrials.gov ont été interrogées, ainsi que les abrégés présentés dans les conférences majeures en traumatologie depuis 2005. La sélection des études et l’extraction des données ont été effectuées en duplicata. Aucune donnée interprétable n’a pu être extraite des études observationnelles et le seul essai clinique identifié n’avait pas une puissance suffisante (RR de mortalité avec vasopresseurs 1.24, IC 95 % 0.64-2.43). Cette synthèse met en lumière l’incertitude scientifique sur le rôle des vasopresseurs en traumatologie. Les vasopresseurs ont des bénéfices potentiels importants, puisqu’ils permettent entre autres de supporter étroitement l’hémodynamie des patients. En revanche, ils présentent aussi un fort potentiel de dangerosité. Ils sont utilisés fréquemment, malgré l’absence de données sur leurs risques et bénéfices. Ces trouvailles établissent clairement la pertinence clinique et le bien-fondé éthique d’un essai clinique sur le rôle des vasopresseurs dans la prise en charge précoce des victimes de traumatismes. / Abstract : Trauma teams often make use of both medical and surgical interventions in the early management of traumatic shock. Vasopressors have an important clinical potential, namely because they allow fluid restriction and narrow hemodynamic support. However, they also have the potential for significant harm. The role of vasopressors in this early phase of care is controversial. Although North American guidelines consider that vasopressors are contraindicated in this clinical setting, some European experts encourage their use in the hopes of reducing intravenous fluid administration and its inherent risks. Before designing an adequate clinical trial on vasopressor use, a number of vital questions must be answered. First, current accepted practice must be described in order to determine how it will compare with an eventual experimental intervention. Second, relevant knowledge gaps in the scientific literature must be identified in order to establish equipoise and refine the research question. Chapter 2 of this document presents an observational study conducted in a regional trauma centre in the province of Québec. This retrospective study documents current practice patterns adopted by trauma teams over the course of 2013, with particular emphasis on vasopressor and intravenous fluid use. Over this timeframe, more than 40 % of patients received vasopressors, most often in the presence of traumatic brain injury (OR 10.2, 95% CI 2.7-38.5). Moreover, these vasopressors were often administered in the very early phases of trauma care, before any significant intravenous fluid loading. Chapter 3 consists of a systematic review on the early use of vasopressors in the management of traumatic shock. MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov were searched, as well as conference proceedings from major trauma meetings since 2005. Independent reviewers completed study selection and data extraction in duplicate. Observational studies yielded no interpretable data, and the only clinical trial addressing the research question had insufficient power to inform clinical practice (RR of death with vasopressor use 1.24, 95% CI 0.64-2.43). This knowledge synthesis highlights the uncertainty surrounding the role of vasopressors in trauma. Trauma teams routinely make use of vasopressors despite the absence of data on their risks and benefits. These findings clearly establish both the clinical impetus and ethical justification for a clinical trial focusing on the early use of vasopressors in the management of traumatic shock.

Seit Veröffentlichung der Studien von G. Van den Berghe et al. im Jahre 2001 galt es die strikte Blutzuckereinstellung in normoglykämische Bereiche bei Schwerverletzten anzustreben. Die intensivierte Insulintherapie wurde daraufhin von verschiedensten Fachgesellschaften in Leitlinien und Therapieregimen integriert, so auch auf der neurochirurgischen ITS der Universitätsklinik Leipzig. Kurze Zeit später erschienen große multizentrische Studien, die den Benefit der intensivierten Insulintherapie in Frage stellten und sogar von einer signifikant höheren Letalität bei strikt normoglykäm eingestellten Patienten berichteten. Daher wird in dieser Studie die zwiespältige aktuelle Datenlage zum Anlass genommen, die Beziehungen zwischen Blutzuckereinstellung und ITS-Regime sowie die Auswirkungen hyperglykämischer Stoffwechselsituationen und mögliche Bedeutung des Blutglukosespiegels respektive der intensivierten Insulintherapie speziell für Patienten mit isoliertem mittelschwerem und schwerem Schädel-Hirn-Trauma zu evaluieren. Mit Hilfe der Integration wird erstmalig ein Verfahren zur Blutglukosedarstellung verwendet, dass durch die Flächenberechnung (Area under the Curve (AUC-BG)) ein Abbild von Höhe und Dauer der Hyperglykämie schafft. Es konnte gezeigt werden, dass die Blutzuckereinstellung mit dem klinischen Verlauf, krankheitsspezifischen Therapiekonzepten, Komplikationen und dem Outcome der Patienten korreliert und positiv Einfluss nimmt. Von besonderem Interesse war die Auswirkung auf den Hirndruck und die Notwendigkeit von Dekompressionskraniektomien, als auch auf Infektionsereignisse, die kontrollierte Beatmung, Ernährungsform und das Outcome. Nach Einführung der intensivierten Insulintherapie wurde ein Vergleich mit konventionell therapierten Patienten herbeigeführt. Es wurden vergleichende Analysen zwischen der retrospektiven (n = 65, konventionelle Insulintherapie, Blutzucker < 10,0 mmol/l [< 180 mg/dl]) und prospektiven Gruppe (n = 65, intensivierte Insulintherapie, Blutzucker 4,4 – 6,1 mmol/l [80 – 110 mg/dl]) bezüglich Blutzuckerfläche, Intensivverlauf und Outcome durchgeführt. Nach 1:1-Matching hinsichtlich Alter und Geschlechterzugehörigkeit waren die beiden Therapiegruppen homogen und es zeigten sich keine Unterschiede bezüglich der Aufnahmecharakteristik. Schädelhirntraumatisierte Patienten profitierten von einer intensivierten Insulintherapie im Vergleich zur Kontrollgruppe, auch wenn es nicht gelang, den Blutzuckerspiegel entsprechend der initiierten Therapierichtlinie signifikant hin zur Normoglykämie zu senken. Die positiven Effekte zeigten sich deutlich in Bezug auf die Infektionsrate und Ernährungsform. Die intensivierte Insulintherapie senkte den Hirndruck und die Rate risikobehafteter Dekompressionskraniektomien mit einem deutlicheren Trend zu besseren Outcomemesswerten. Vor allem Patienten mit einem besseren initialem GCS und Nicht-Diabetiker scheinen von einer guten Blutzuckereinstellung zu profitieren. Hypoglykämien (Blutzucker ≤ 3 mmol/l) traten entgegen der Vermutung dabei nicht gehäuft auf und stellten somit kein Gegenargument einer derartigen Therapie dar. Die Senkung des Blutzuckers in einen moderaten, therapeutischen Bereich sollte das Mindestziel in der Gesamttherapie von Patienten mit einem mittelschweren und schweren Schädel-Hirn-Trauma sein, wobei ein Konsens über den optimal therapeutischen Blutzuckerzielbereich bisher noch nicht gefunden wurde und somit weitere Untersuchungen gerechtfertigt sind.