The incidence and impact of 'Tandem Neurotrauma'.

Introduction: The epidemiology and prognosis of the isolated traumatic brain injury (TBI) and spinal cord injury (SCI) are well studied. However, the knowledge of the impact of concurrent neurotrauma is very limited. Research questions: To characterize the longitudinal incidence of concurrent TBI and SCI and to investigate their combined impact on clinical care and outcomes, compared to a comparative but isolated SCI or TBI. Materials and methods: Data from 167,793 patients in the Trauma Audit and Research Network (TARN) registry collected in England and Wales between 2008 and 2018 were analysed. Tandem neurotrauma was defined as patients with concurrent TBI and SCI. The patient with isolated TBI or SCI was matched to the patient with tandem neurotrauma using propensity scores. Results: The incidence of tandem neurotrauma increased tenfold between 2008 and 2018, from 0.21 to 2.21 per 100,000 person-years. Patients in the tandem neurotrauma group were more likely to require multiple surgeries, ICU admission, longer ICU and hospital LOS, higher 30-day mortality, and were more likely to be transferred to acute hospitals and rehabilitation or suffer death at discharge, compared to patients with isolated TBI. Likewise, individuals with tandem neurotrauma compared to those with isolated SCI had a higher tendency to receive more than one surgery, ICU admission, longer LOS for ICU and higher mortality either at 30-day follow-up or at discharge. Discussion and conclusions: The incidence of tandem neurotrauma has increased steadily during the past decade. Its occurrence leads to greater mortality and care requirements, particularly when compared to TBI alone. Further investigations are warranted to improve outcomes in tandem neurotrauma.

Traumatic Brain Injury in Cameroon: A Prospective Observational Study in a Level I Trauma Centre.

Background and Objective: About 14 million people will likely suffer a traumatic brain injury (TBI) per year by 2050 in sub-Saharan Africa. Studying TBI characteristics and their relation to outcomes can identify initiatives to improve TBI prevention and care. The objective of this study was to define the features and outcomes of TBI patients seen over a 1-year period in a level-I trauma centre in Cameroon. Materials and Methods: Data on demographics, causes, clinical aspects, and discharge status were collected over a period of 12 months. The Glasgow Outcome Scale-Extended (GOSE) and the Quality-of-Life Questionnaire after Brain Injury (QoLIBRI) were used to evaluate outcomes six months after TBI. Comparisons between two categorical variables were done using Pearson's chi-square test. Results: A total of 160 TBI patients participated in the study. The age group 15-45 years was most represented (78%). Males were more affected (90%). A low educational level was seen in 122 (76%) cases. Road traffic incidents (RTI) (85%), assaults (7.5%), and falls (2.5%) were the main causes of TBI, with professional bike riders being frequently involved (27%). Only 15 patients were transported to the hospital by ambulance, and 14 of these were from a referring hospital. CT-imaging was performed in 78% of cases, and intracranial traumatic abnormalities were identified in 64% of cases. Financial constraints (93%) was the main reason for not performing a CT scan. Forty-six (33%) patients were discharged against medical advice (DAMA) due to financial constraints. Mortality was 14% (22/160) and high in patients with severe TBI (46%). DAMA had poor outcomes with QoLIBRI. Only four patients received post-injury physical therapy services. Conclusions: TBI in Cameroon mainly results from RTIs and commonly affects young adult males. Lack of pre-hospital care, financial constraints limiting both CT scanning and medical care, and a lack of acute physiotherapy services likely influenced care and outcomes adversely.

Comparative effectiveness of decompressive craniectomy versus craniotomy for traumatic acute subdural hematoma (CENTER-TBI): an observational cohort study.

Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014-2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12-26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p < 0.0001). Higher centre preference for DC over craniotomy was not associated with better functional outcome (adjusted common odds ratio (OR) per 14% [IQR increase] more DC in a centre = 0.9 [95% CI 0.7-1.1], n = 200). Primary DC was associated with more follow-on surgeries and complications [secondary cranial surgery 27% vs. 18%; shunts 11 vs. 5%]; and similar odds of in-hospital mortality (adjusted OR per 14% IQR more primary DC 1.3 [95% CI (1.0-3.4), n = 200]). Interpretation: We found substantial practice variation in the employment of DC over craniotomy for ASDH. This variation in treatment strategy did not result in different functional outcome. These findings suggest that primary DC should be restricted to salvageable patients in whom immediate replacement of the bone flap is not possible due to intraoperative brain swelling. Funding: Hersenstichting Nederland for the Dutch NeuroTraumatology Quality Registry and the European Union Seventh Framework Program.

Early neuro-rehabilitation in traumatic brain injury: the need for an African perspective.

BACKGROUND: Traumatic brain injury (TBI) is a global public health challenge, affecting about 69 million individuals annually and being one of the leading causes of mortality. It has adverse consequences in terms of cognitive and physical functioning, which makes rehabilitation interventions an integral part of its management. Early neuro-rehabilitation guidelines for traumatic brain injury have not yet been developed and implemented in most of Africa especially Sub-Saharan Africa. BODY: We aimed with this Opinion to propose a collective reflection on the development and implementation of early neuro-rehabilitation guidelines as an integral part of the care in traumatic brain injury. The different aspects to be considered for reflection have been highlighted: Traumatic brain injury severity to be considered in early neuro-rehabilitation; who should be assessed and receive early neurorehabilitation, barriers to be considered for early neurorehabilitation; what early neurorehabilitation to be considered; the different phases involved in rehabilitation after mild, moderate, and severe TBI; and lastly, what perspective for the creation of neurorehabilitation teams. In conclusion, neuro-rehabilitation should start at the time of admission and should continue from the intensive care unit through the community for the moderate-to-severe traumatic brain injury population. However, mild TBI should also be considered for long-term follow-up in the community due to the fact that some mild traumatic brain injury patients might develop chronic cognitive problems or fatigue with time. CONCLUSION: Neurorehabilitation should start at the time of admission and continue from the intensive care unit through the community for the moderate-to-severe traumatic brain injury population. There is a need to develop, agree on, and implement guidelines on early neuro-rehabilitation interventions for patients with moderate to severe traumatic brain injury in the African region, where disparities in care are common reality.

Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES).

BACKGROUND: Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care. METHODS: A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted. RESULTS: A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided. CONCLUSIONS: This consensus provides practical recommendations to support clinician's decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.

Comparison of health-related quality of life in patients with traumatic brain injury, subarachnoid haemorrhage and cervical spine disease.

PURPOSE: The degree of disability that is acceptable to patients following traumatic brain injury (TBI) continues to be debated. While the dichotomization of outcome on the Glasgow Outcome Score (GOSE) into 'favourable' and 'unfavourable' continues to guide clinical decisions, this may not reflect an individual's subjective experience. The aim of this study is to assess how patients' self-reported quality of life (QoL) relates to objective outcome assessments and how it compares to other debilitating neurosurgical pathologies, including subarachnoid haemorrhage (SAH) and cervical myelopathy. METHOD: A retrospective analysis of over 1300 patients seen in Addenbrooke's Hospital, Cambridge, UK with TBI, SAH and patients pre- and post- cervical surgery was performed. QoL was assessed using the SF-36 questionnaire. Kruskal-Wallis test was used to analyse the difference in SF-36 domain scores between the four unpaired patient groups. To determine how the point of dichotomization of GOSE into 'favourable' and 'unfavourable' outcome affected QOL, SF-36 scores were compared between GOSE and mRS. RESULTS: There was a statistically significant difference in the median Physical Component Score (PCS) and Mental Component Score (MCS) of SF-36 between the three neurosurgical pathologies. Patients with TBI and SAH scored higher on most SF-36 domains when compared with cervical myelopathy patients in the severe category. While patients with Upper Severe Disability on GOSE showed significantly higher PC and MC scores compared to GOSE 3, there was a significant degree of variability in individual responses across the groups. CONCLUSION: A significant number of patients following TBI and SAH have better self-reported QOL than cervical spine patients and patients' subjective perception and expectations following injury do not always correspond to objective disability. These results can guide discussion of treatment and outcomes with patients and families.

Cell-Free Mitochondrial DNA in Acute Brain Injury.

Traumatic brain injury and aneurysmal subarachnoid haemorrhage are a major cause of morbidity and mortality worldwide. Treatment options remain limited and are hampered by our understanding of the cellular and molecular mechanisms, including the inflammatory response observed in the brain. Mitochondrial DNA (mtDNA) has been shown to activate an innate inflammatory response by acting as a damage-associated molecular pattern (DAMP). Here, we show raised circulating cell-free (ccf) mtDNA levels in both cerebrospinal fluid (CSF) and serum within 48 h of brain injury. CSF ccf-mtDNA levels correlated with clinical severity and the interleukin-6 cytokine response. These findings support the use of ccf-mtDNA as a biomarker after acute brain injury linked to the inflammatory disease mechanism.

Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells.

Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature. Indeed, GBM-derived CD11b+ microglia/macrophages were necessary and sufficient to protect progenitors against ZIKV infection in a non-cell autonomous manner. Using SOX2+ GBM cell lines, we found that CD11b+-conditioned medium containing type 1 interferon beta (IFNß) promoted progenitor resistance to ZIKV, whereas inhibition of JAK1/2 signaling restored productive infection. Additionally, CD11b+ conditioned medium, and IFNß treatment rendered HDB progenitor lines and explants refractory to ZIKV. These findings provide insight into neuroprotection for HDB progenitors as well as enhanced GBM oncolytic therapies.

Demographics, Causes, and Outcome of Traumatic Brain Injury among Trauma Cases in Cameroon: A Multi-Center Five Year's Retrospective Study.

Traumatic brain injury (TBI) is a huge public health challenge worldwide. Epidemiological monitoring is important to inform healthcare policy. We aimed at determining the prevalence, outcome, and causes of TBI in Cameroon by conducting a 5-year retrospective study in three referral trauma centers. Data on demographics, causes, injury mechanisms, clinical aspects, and discharge status were recorded. Comparisons between two categorical variables were done using Pearson's chi-square test or Fisher's exact test. A total of 6248 cases of TBI were identified of 18,151 trauma cases, yielding a prevalence of 34%. The number of TBI cases increased across the years (915 in 2016, 1406 in 2020). Demographic data and causes of TBI were available for 6248 subjects and detailed data on clinical characteristics on 2178 subjects. Median age was 30.0 (24.0, 41.0) years. Males were more affected (80%). Road traffic incidents (RTIs; 75%) was the main cause of TBI, with professional bike riders being more affected (17%). Computed tomography (CT) imaging was performed in 67.7% of cases. Of the 597 (27.4%) cases who did not undergo neuroimaging, 311 (52.1%) did not have neuroimaging performed because of financial constraints, among which 7% were severe TBI cases. A total of 341 (19.6%) patients were discharged against medical advice, of which 83% had financial limitations. Mortality was 10.3% (225 of 2178) in the overall population, but disproportionately high in patients with severe TBI (55%) compared to those in high-income settings (27%). TBI occurrence is high in Cameroon, and RTIs are the main causes. Disparities in care provision were identified as attributable to financial constraints regarding CT scanning and continuation of care. The data presented can inform preventive interventions to improve care provision and transport policies. Implementation of a universal health insurance may be expected to improve hospital care and reduce the adverse effects of TBI among Cameroonians.

Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury.

BACKGROUND: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. METHODS: TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. RESULTS: Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. CONCLUSIONS: Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations.

The Relative Merits of Posterior Surgical Treatments for Multi-Level Degenerative Cervical Myelopathy Remain Uncertain: Findings from a Systematic Review.

OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments.

Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury.

Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2-5, and Days 6-12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho -0.33, P < 0.001) and microdialysis glucose (Rho -0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.

Prevention of road traffic collisions and associated neurotrauma in Colombia: An exploratory qualitative study.

INTRODUCTION: Neurotrauma is an important but preventable cause of death and disability worldwide, with the majority being associated with road traffic collisions (RTCs). The greatest burden is seen in low -and middle- income countries (LMICs) where variations in the environment, infrastructure, population and habits can challenge the success of conventional preventative approaches. It is therefore necessary to understand local perspectives to allow for the development and implementation of context-specific strategies which are effective and sustainable. METHODS: This study took place in Colombia where qualitative data collection was carried out with ten key informants between October and November 2019. Semi-structured interviews were conducted and explored perceptions on RTCs and neurotrauma, preventative strategies and interventions, and the role of research in prevention. Interview transcripts were analysed by thematic analysis using a framework approach. RESULTS: Participants' confirmed that RTCs are a significant problem in Colombia with neurotrauma as an important outcome. Human and organisational factors were identified as key causes of the high rates of RTCs. Participants described the current local preventative strategies, but were quick to discuss limitations and challenges to their success. Key barriers reported were poor attitudes and knowledge, particularly in the community. Suggestions were provided on ways to improve prevention through better education and awareness, stricter enforcement and new policies on prevention, proper budgeting and resource allocation, as well as through collaboration and changes in attitudes and leadership. Participants identified four key research areas they felt would influence prevention of RTCs and associated neurotrauma: causes of RTCs; consequences and impact of RTCs; public involvement in research; improving prevention. CONCLUSION: RTCs are a major problem in Colombia despite the current preventative strategies and interventions. Findings from this study have a potential to influence policy, practice and research by illustrating different solutions to the challenges surrounding prevention and by highlighting areas for further research.

An exploratory qualitative study of the prevention of road traffic collisions and neurotrauma in India: perspectives from key informants in an Indian industrial city (Visakhapatnam).

BACKGROUND: Despite current preventative strategies, road traffic collisions (RTCs) and resultant neurotrauma remain a major problem in India. This study seeks to explore local perspectives in the context within which RTCs take place and identify potential suggestions for improving the current status. METHODS: Ten semi-structured interviews were carried out with purposively selected key informants from the city of Visakhapatnam, Andhra Pradesh. Participants were from one of the following categories: commissioning stakeholders; service providers; community or local patient group/advocacy group representatives. Transcripts from these interviews were analysed qualitatively using the Framework Method. RESULTS: Participants felt RTCs are a serious problem in India and a leading cause of neurotrauma. Major risk factors identified related to user behaviour such as speeding and not using personal safety equipment, and the user state, namely drink driving and underage driving. Other reported risk factors included poor infrastructure, moving obstacles on the road such as other vehicles, pedestrians and animals, overloaded vehicles and substandard safety equipment. Participants discussed how RTCs affect not only the health of the casualty, but are also a burden to the healthcare system, families, and the national economy. Although there are ongoing preventative strategies being carried out by both the government and the community, challenges to successful prevention emerged from the interviews which included resource deficiencies, inconsistent implementation, lack of appropriate action, poor governance, lack of knowledge and the mindset of the community and entities involved in prevention. Recommendations were given on how prevention of RTCs and neurotrauma might be improved, addressing the areas of education and awareness, research, the pre-hospital and trauma systems, enforcement and legislation, and road engineering, in addition to building collaborations and changing mindsets. CONCLUSIONS: RTCs remain a major problem in India and a significant cause of neurotrauma. Addressing the identified gaps and shortfalls in current approaches and reinforcing collective responsibility towards road safety would be the way forward in improving prevention and reducing the burden.

Robotic Semi-Automated Transcranial Doppler Assessment of Cerebrovascular Autoregulation in Post-Concussion Syndrome: Methodological Considerations.

Post-concussion syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence and impact, the underlying mechanisms of PCS are unclear. We hypothesized that impaired cerebral autoregulation (CA) is a contributor. In this article, we present our protocol for non-invasively assessing CA in patients with TBI and PCS in a real-world clinical setting. A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical center. Data points included: demographics, symptom profile (Post-Concussion Symptom Scale [PCSS]) and neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]). Cerebrovascular metrics (nMxa co-efficient and the transient hyperaemic-response ratio [THRR]) were collected using transcranial Doppler (TCD), finger plethysmography, and bespoke software (ICM+). Twelve participants were initially recruited but 2 were excluded after unsuccessful insonation of the middle cerebral artery (MCA); 10 participants (5 patients with TBI, 5 healthy controls) were included in the analysis (median age 26.5 years, male to female ratio: 7:3). Median PCSS scores were 6/126 for the TBI patient sub-groups. Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). nMxa was calculated for 90% of included patients, whereas THRR was calculated for 50%. Median study time was 127.5 min and feedback (n = 6) highlighted the perceived acceptability of the study. This pilot study has demonstrated a reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. This protocol is feasible and is acceptable to participants. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI.

Bedside EEG predicts longitudinal behavioural changes in disorders of consciousness.

Providing an accurate prognosis for prolonged disorder of consciousness (pDOC) patients remains a clinical challenge. Large cross-sectional studies have demonstrated the diagnostic and prognostic value of functional brain networks measured using high-density electroencephalography (hdEEG). Nonetheless, the prognostic value of these neural measures has yet to be assessed by longitudinal follow-up. We address this gap by assessing the utility of hdEEG to prognosticate long-term behavioural outcome, employing longitudinal data collected from a cohort of patients assessed systematically with resting hdEEG and the Coma Recovery Scale-Revised (CRS-R) at the bedside over a period of two years. We used canonical correlation analysis to relate clinical (including CRS-R scores combined with demographic variables) and hdEEG variables to each other. This analysis revealed that the patient's age, and the hdEEG theta band power and alpha band connectivity, contributed most significantly to the relationship between hdEEG and clinical variables. Further, we found that hdEEG measures recorded at the time of assessment augmented clinical measures in predicting CRS-R scores at the next assessment. Moreover, the rate of hdEEG change not only predicted later changes in CRS-R scores, but also outperformed clinical measures in terms of prognostic power. Together, these findings suggest that improvements in functional brain networks precede changes in behavioural awareness in pDOC. We demonstrate here that bedside hdEEG assessments conducted at specialist nursing homes are feasible, have clinical utility, and can complement clinical knowledge and systematic behavioural assessments to inform prognosis and care.

Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years.

BACKGROUND: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials. OBJECTIVE: To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling. METHODS: Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years. RESULTS: Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3-6 months. INTERPRETATION: Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment.

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

OBJECTIVE: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI. PARTICIPANTS/SETTING: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99). DESIGN: Case-control observational study. MAIN MEASURES: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility. RESULTS: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI. CONCLUSION: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.