Publications by authors named "Peter J A Hutchinson"

51 Publications

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).

BMC Public Health 2021 03 30;21(1):618. Epub 2021 Mar 30.

NIHR Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1186/s12889-021-10686-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008519PMC
March 2021

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

PLoS One 2021 25;16(3):e0249004. Epub 2021 Mar 25.

NIHR Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249004PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993809PMC
March 2021

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

Neurotrauma Rep 2020 25;1(1):218-231. Epub 2020 Nov 25.

Division of Neurosurgery, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

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 ( = 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.
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http://dx.doi.org/10.1089/neur.2020.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703686PMC
November 2020

Bedside EEG predicts longitudinal behavioural changes in disorders of consciousness.

Neuroimage Clin 2020 5;28:102372. Epub 2020 Aug 5.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; School of Computing, University of Kent, Canterbury, United Kingdom.

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.
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http://dx.doi.org/10.1016/j.nicl.2020.102372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426558PMC
August 2020

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

J Neurol 2020 Nov 13;267(11):3223-3234. Epub 2020 Jun 13.

Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/s00415-020-09979-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578150PMC
November 2020

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

J Head Trauma Rehabil 2020 Nov/Dec;35(6):E513-E523

University Division of Anaesthesia, Department of Medicine (Drs Carroll, Menon, and Newcombe and Mss Manktelow, Outtrim, Chatfield, and Forsyth), Academic Department of Neurosurgery, Department of Clinical Neurosciences (Dr Hutchinson), Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (Drs Sahakian, Menon, and Newcombe), Department of Psychiatry (Dr Sahakian), and Behavioural & Clinical Neuroscience Institute (Dr Sahakian), University of Cambridge, Cambridge, United Kingdom; Turku Brain Injury Center, University of Turku, Turku, Finland (Drs Tenovuo and Posti); Turku University Hospital, Turku, Finland (Drs Tenovuo and Posti); Department of Neurosurgery, Turku University Hospital, Turku, Finland (Dr Posti); and Division of Psychology, University of Stirling, Stirling, United Kingdom (Dr Wilson).

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.
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http://dx.doi.org/10.1097/HTR.0000000000000575DOI Listing
May 2020

Mapping global evidence on strategies and interventions in neurotrauma and road traffic collisions prevention: a scoping review.

Syst Rev 2020 05 20;9(1):114. Epub 2020 May 20.

NIHR Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, UK.

Background: Neurotrauma is an important global health problem. The largest cause of neurotrauma worldwide is road traffic collisions (RTCs), particularly in low- and middle-income countries (LMICs). Neurotrauma and RTCs are preventable, and many preventative interventions have been implemented over the last decades, especially in high-income countries (HICs). However, it is uncertain if these strategies are applicable globally due to variations in environment, resources, population, culture and infrastructure. Given this issue, this scoping review aims to identify, quantify and describe the evidence on approaches in neurotrauma and RTCs prevention, and ascertain contextual factors that influence their implementation in LMICs and HICs.

Methods: A systematic search was conducted using five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health on EBSCO host, Cochrane Database of Systematic Reviews), grey literature databases, government and non-government websites, as well as bibliographic and citation searching of selected articles. The extracted data were presented using figures, tables, and accompanying narrative summaries. The results of this review were reported using the PRISMA Extension for Scoping Reviews (PRISMA-ScR).

Results: A total of 411 publications met the inclusion criteria, including 349 primary studies and 62 reviews. More than 80% of the primary studies were from HICs and described all levels of neurotrauma prevention. Only 65 papers came from LMICs, which mostly described primary prevention, focussing on road safety. For the reviews, 41 papers (66.1%) reviewed primary, 18 tertiary (29.1%), and three secondary preventative approaches. Most of the primary papers in the reviews came from HICs (67.7%) with 5 reviews on only LMIC papers. Fifteen reviews (24.1%) included papers from both HICs and LMICs. Intervention settings ranged from nationwide to community-based but were not reported in 44 papers (10.8%), most of which were reviews. Contextual factors were described in 62 papers and varied depending on the interventions.

Conclusions: There is a large quantity of global evidence on strategies and interventions for neurotrauma and RTCs prevention. However, fewer papers were from LMICs, especially on secondary and tertiary prevention. More primary research needs to be done in these countries to determine what strategies and interventions exist and the applicability of HIC interventions in LMICs.
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http://dx.doi.org/10.1186/s13643-020-01348-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240915PMC
May 2020

Continuous cerebrovascular reactivity monitoring in moderate/severe traumatic brain injury: a narrative review of advances in neurocritical care.

Br J Anaesth 2020 Jan 23. Epub 2020 Jan 23.

Department of Intensive Care, Maastricht UMC, Maastricht, the Netherlands.

Impaired cerebrovascular reactivity in adult moderate and severe traumatic brain injury (TBI) is known to be associated with worse global outcome at 6-12 months. As technology has improved over the past decades, monitoring of cerebrovascular reactivity has shifted from intermittent measures, to experimentally validated continuously updating indices at the bedside. Such advances have led to the exploration of individualised physiologic targets in adult TBI management, such as optimal cerebral perfusion pressure (CPP) values, or CPP limits in which vascular reactivity is relatively intact. These targets have been shown to have a stronger association with outcome compared with existing consensus-based guideline thresholds in severe TBI care. This has sparked ongoing prospective trials of such personalised medicine approaches in adult TBI. In this narrative review paper, we focus on the concept of cerebral autoregulation, proposed mechanisms of control and methods of continuous monitoring used in TBI. We highlight multimodal cranial monitoring approaches for continuous cerebrovascular reactivity assessment, physiologic and neuroimaging correlates, and associations with outcome. Finally, we explore the recent 'state-of-the-art' advances in personalised physiologic targets based on continuous cerebrovascular reactivity monitoring, their benefits, and implications for future avenues of research in TBI.
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http://dx.doi.org/10.1016/j.bja.2019.11.031DOI Listing
January 2020

Longitudinal assessments highlight long-term behavioural recovery in disorders of consciousness.

Brain Commun 2019 16;1(1):fcz017. Epub 2019 Sep 16.

Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.

Accurate diagnosis and prognosis of disorders of consciousness is complicated by the variability amongst patients' trajectories. However, the majority of research and scientific knowledge in this field is based on cross-sectional studies. The translational gap in applying this knowledge to inform clinical management can only be bridged by research that systematically examines follow-up. In this study, we present findings from a novel longitudinal study of the long-term recovery trajectory of 39 patients, repeatedly assessed using the Coma Recovery Scale-Revised once every 3 months for 2 years, generating 185 assessments. Despite the expected inter-patient variability, there was a statistically significant improvement in behaviour over time. Further, improvements began approximately 22 months after injury. Individual variation in the trajectory of recovery was influenced by initial diagnosis. Patients with an initial diagnosis of unresponsive wakefulness state, who progressed to the minimally conscious state, did so at a median of 485 days following onset-later than 12-month period after which current guidelines propose permanence. Although current guidelines are based on the expectation that patients with traumatic brain injury show potential for recovery over longer periods than those with non-traumatic injury, we did not observe any differences between trajectories in these two subgroups. However, age was a significant predictor, with younger patients showing more promising recovery. Also, progressive increases in arousal contributed exponentially to improvements in behavioural awareness, especially in minimally conscious patients. These findings highlight the importance of indexing arousal when measuring awareness, and the potential for interventions to regulate arousal to aid long-term behavioural recovery in disorders of consciousness.
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http://dx.doi.org/10.1093/braincomms/fcz017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924536PMC
September 2019

Mapping global evidence on strategies and interventions in neurotrauma and road traffic collisions prevention: a scoping review protocol.

BMJ Open 2019 11 12;9(11):e031517. Epub 2019 Nov 12.

NIHR Global Health Research Group on Neurotrauma, University of Cambridge, Cambridge, Cambridgeshire, UK.

Introduction: Neurotrauma is an important global health problem. This 'silent epidemic' is a major cause of death and disability in adolescents and young adults, with significant societal and economic impacts. Globally, the largest cause of neurotrauma is road traffic collisions (RTCs). Neurotrauma and RTCs are largely preventable, and many preventative strategies and interventions have been established and implemented over the last decades, particularly in high-income countries. However, these approaches may not be applicable globally, due to variations in environment, resources, population, culture and infrastructure. This paper outlines the protocol for a scoping review, which seeks to map the evidence on strategies and interventions in neurotrauma and RTCs prevention globally, and to ascertain contextual factors that influence their implementation.

Methods And Analysis: This scoping review will use the established methodology by Arksey and O'Malley. Eligible studies will be identified from five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health/EBSCO and Cochrane Database of Systematic Reviews) and grey literature sources. We will also carry out bibliographical and citation searching of included studies. A two-stage selection process, which involves screening of titles and abstracts, followed by full-text screening, will be used to determine eligible studies which will undergo data abstraction using a customised, piloted data extraction sheet. The extracted data will be presented using evidence mapping and a narrative summary.

Ethics And Dissemination: Ethical approval is not required for this scoping review, which is the first step in a multiphase public health research project on the global prevention of neurotrauma. The final review will be submitted for publication to a scientific journal, and results will be presented at appropriate conferences, workshops and meetings. Protocol registered on 5 April 2019 with Open Science Framework (https://osf.io/s4zk3/).
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http://dx.doi.org/10.1136/bmjopen-2019-031517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858136PMC
November 2019

Dextran 500 Improves Recovery of Inflammatory Markers: An Microdialysis Study.

J Neurotrauma 2020 01 6;37(1):106-114. Epub 2019 Aug 6.

Division of Neurosurgery, Department of Clinical Neurosciences, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Cerebral microdialysis (CMD) is used in severe traumatic brain injury (TBI) in order to recover metabolites in brain extracellular fluid (ECF). To recover larger proteins and avoid fluid loss, albumin supplemented perfusion fluid (PF) has been utilized, but because of regulatory changes in the European Union, this is no longer practicable. The aim with this study was to see whether fluid, absolute (AR), and relative (RR) recovery for the novel carrier, Dextran 500, was better than conventional PF for a range of cytokines and chemokines. An setup mimicking conditions observed in the neurocritical care of TBI patients was used, utilizing 100-kDa molecular-weight cut-off CMD catheters inserted through a triple-lumen bolt cranial access device into an external solution with diluted cytokine standards in known concentrations for 48 h (divided into 6-h epochs). Samples were run on a 39-plex Luminex (Luminex Corporation, Austin, TX) assay to assess cytokine concentrations. We found that fluid recovery was inadequate in 50% of epochs with conventional PF, whereas Dextran PF overcame this limitation. The AR was higher in the Dextran PF samples for a majority of cytokines, and RR was significantly increased for macrophage colony-stimulating factor and transforming growth factor-alpha. In summary, Dextran PF improved fluid and cytokine recovery as compared to conventional PF and is a suitable alternative to albumin supplemented PF for protein microdialysis.
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http://dx.doi.org/10.1089/neu.2019.6513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921287PMC
January 2020

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

Sci Rep 2019 04 10;9(1):5885. Epub 2019 Apr 10.

Department of Clinical Neurosciences, Western General Hospitals NHS Trust, Crewe Road, Edinburgh, EH4 2XU, UK.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.
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http://dx.doi.org/10.1038/s41598-019-42087-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458174PMC
April 2019

Glucose Dynamics of Cortical Spreading Depolarization in Acute Brain Injury: A Systematic Review.

J Neurotrauma 2019 07 28;36(14):2153-2166. Epub 2019 Mar 28.

1 Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.

Cortical spreading depolarization (CSD) is an emerging mode of secondary neuronal damage in acute brain injury (ABI). Subsequent repolarisation is a metabolic process requiring glucose. Instances of CSD and glucose derangement are both linked to poor neurological outcome, but their causal inter-relationship is not fully defined. This systematic review seeks to evaluate the available human evidence studying CSD and glucose to further understand their dynamic relationship. We conducted a systematic review of studies examining CSD through electrocorticography and cerebral/systemic glucose concentrations in ABI, excluding animal studies. The search yielded 478 articles, of which 13 were eligible. Across 10 manuscripts, 125 patients received simultaneous monitoring, with 1987 CSD episodes observed. Eight of 10 studies observed correlation between CSD and glucose change. Seven of eight studies observed possible cumulative effect of recurrent CSD on glucose derangement and two identified correlation between glycopenia and incidence of CSD. These findings confirm a relationship between CSD and glucose, and suggest it may be cyclical, where CSD causes local glycopenia, which may potentiate further CSD. Positive observations were not common to all studies, likely due to differing methodology or heterogeneity in CSD propensity. Further study is required to delineate the utility of the clinical modulation of serum and cerebral glucose to alter the propensity for CSD following brain injury.
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http://dx.doi.org/10.1089/neu.2018.6175DOI Listing
July 2019

Twenty-Five Years of Intracranial Pressure Monitoring After Severe Traumatic Brain Injury: A Retrospective, Single-Center Analysis.

Neurosurgery 2019 07;85(1):E75-E82

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.

Background: Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets.

Objective: To describe the changes in intracranial monitoring variables over the past 25 yr.

Methods: Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017.

Results: CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%).

Conclusion: We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged.
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http://dx.doi.org/10.1093/neuros/nyy468DOI Listing
July 2019

Longitudinal Bedside Assessments of Brain Networks in Disorders of Consciousness: Case Reports From the Field.

Front Neurol 2018 21;9:676. Epub 2018 Aug 21.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Clinicians are regularly faced with the difficult challenge of diagnosing consciousness after severe brain injury. As such, as many as 40% of minimally conscious patients who demonstrate fluctuations in arousal and awareness are known to be misdiagnosed as unresponsive/vegetative based on clinical consensus. Further, a significant minority of patients show evidence of hidden awareness not evident in their behavior. Despite this, clinical assessments of behavior are commonly used as bedside indicators of consciousness. Recent advances in functional high-density electroencephalography (hdEEG) have indicated that specific patterns of resting brain connectivity measured at the bedside are strongly correlated with the re-emergence of consciousness after brain injury. We report case studies of four patients with traumatic brain injury who underwent regular assessments of hdEEG connectivity and Coma Recovery Scale-Revised (CRS-R) at the bedside, as part of an ongoing longitudinal study. The first, a patient in an unresponsive wakefulness state (UWS), progressed to a minimally-conscious state several years after injury. HdEEG measures of alpha network centrality in this patient tracked this behavioral improvement. The second patient, contrasted with patient 1, presented with a persistent UWS diagnosis that paralleled with stability on the same alpha network centrality measure. Patient 3, diagnosed as minimally conscious minus (MCS-), demonstrated a significant late increase in behavioral awareness to minimally conscious plus (MCS+). This patient's hdEEG connectivity across the previous 18 months showed a trajectory consistent with this increase alongside a decrease in delta power. Patient 4 contrasted with patient 3, with a persistent MCS- diagnosis that was similarly tracked by consistently high delta power over time. Across these contrasting cases, hdEEG connectivity captures both stability and recovery of behavioral trajectories both within and between patients. Our preliminary findings highlight the feasibility of bedside hdEEG assessments in the rehabilitation context and suggest that they can complement clinical evaluation with portable, accurate and timely generation of brain-based patient profiles. Further, such hdEEG assessments could be used to estimate the potential utility of complementary neuroimaging assessments, and to evaluate the efficacy of interventions.
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http://dx.doi.org/10.3389/fneur.2018.00676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110818PMC
August 2018

The relationship between neurosurgical instruments and disease transmission: Society of British Neurological Surgeons perspective.

Acta Neuropathol 2018 06 3;135(6):969-971. Epub 2018 May 3.

Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK.

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http://dx.doi.org/10.1007/s00401-018-1858-3DOI Listing
June 2018

Unpicking the Gordian knot: a systems approach to traumatic brain injury care in low-income and middle-income countries.

BMJ Glob Health 2018 25;3(2):e000768. Epub 2018 Mar 25.

NIHR Global Health Research Group for Neurotrauma, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1136/bmjgh-2018-000768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873538PMC
March 2018

Outcome Measures for Baro-Challenge-Induced Eustachian Tube Dysfunction: A Systematic Review.

Otol Neurotol 2018 02;39(2):138-149

University of Cambridge School of Clinical Medicine.

Objectives: Baro-challenge-induced Eustachian tube dysfunction (baro-induced ETD) is characterized by failure of the Eustachian tube (ET) to open adequately to permit middle-ear pressure regulation during ambient pressure changes. There are no well-characterized tests for identifying the condition, which makes both patient diagnosis and research into treatment efficacy challenging. This systematic review evaluates ET function tests as potential outcome measures for baro-induced ETD.

Data Sources: MEDLINE and CENTRAL were searched (database inception to March 2017) and reference lists reviewed for all relevant English Language articles.

Study Selection: Tests in included studies were required to measure ET function in patients reporting baro-induced ear symptoms or barotrauma.

Data Extraction: Data were extracted in a standardized manner, and studies assessed according to Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. The primary outcome of interest was the accuracy of ET function tests.

Data Synthesis: Heterogeneity of subject demographics, ET function test methodology, and reference standards only permitted narrative systematic review.

Conclusion: Sixteen studies involving seven different types of ET function tests were identified. The nine-step test was the most commonly used outcome measure, with overall test sensitivity and specificity ranges of 37 to 100% and 57 to 100%, respectively. Tympanometry test sensitivity was consistently poor (0-50%) while specificity was higher (52-97%). Published accuracy data for other ET function tests and test combinations were limited. Currently, no single test can be recommended for use in clinical practice. A combination of the nine-step test with other objective tests or patient-reported measures appears most promising as a core set of outcome measures for baro-induced ETD.
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http://dx.doi.org/10.1097/MAO.0000000000001666DOI Listing
February 2018

Optimal Cerebral Perfusion Pressure in Centers With Different Treatment Protocols.

Crit Care Med 2018 03;46(3):e235-e241

Department of Critical Care, Maastricht University Medical Center, Maastricht University, The Netherlands.

Objectives: The three centers in this study have different policies regarding cerebral perfusion pressure targets and use of vasopressors in traumatic brain injury patients. The aim was to determine if the different policies affected the estimation of cerebral perfusion pressure which optimizes the strength of cerebral autoregulation, termed "optimal cerebral perfusion pressure."

Design: Retrospective analysis of prospectively collected data.

Setting: Three neurocritical care units at university hospitals in Cambridge, United Kingdom, Groningen, the Netherlands, and Uppsala, Sweden.

Patients: A total of 104 traumatic brain injury patients were included: 35 each from Cambridge and Groningen, and 34 from Uppsala.

Interventions: None.

Measurements And Main Results: In Groningen, the cerebral perfusion pressure target was greater than or equal to 50 and less than 70 mm Hg, in Uppsala greater than or equal to 60, and in Cambridge greater than or equal to 60 or preferably greater than or equal to 70. Despite protocol differences, median cerebral perfusion pressure for each center was above 70 mm Hg. Optimal cerebral perfusion pressure was calculated as previously published and implemented in the Intensive Care Monitoring+ software by the Cambridge group, now replicated in the Odin software in Uppsala. Periods with cerebral perfusion pressure above and below optimal cerebral perfusion pressure were analyzed, as were absolute difference between cerebral perfusion pressure and optimal cerebral perfusion pressure and percentage of monitoring time with a valid optimal cerebral perfusion pressure. Uppsala had the highest cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Uppsala patients were older than the other centers, and age is positively correlated with cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Optimal cerebral perfusion pressure was significantly lower in Groningen than in Cambridge. There were no significant differences in percentage of monitoring time with valid optimal cerebral perfusion pressure. Summary optimal cerebral perfusion pressure curves were generated for the combined patient data for each center. These summary curves could be generated for Groningen and Cambridge, but not Uppsala. The older age of the Uppsala patient cohort may explain the absence of a summary curve.

Conclusions: Differences in optimal cerebral perfusion pressure calculation were found between centers due to demographics (age) and treatment (cerebral perfusion pressure targets). These factors should be considered in the design of trials to determine the efficacy of autoregulation-guided treatment.
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http://dx.doi.org/10.1097/CCM.0000000000002930DOI Listing
March 2018

Corrigendum: Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications.

Front Neurol 2017 1;8:642. Epub 2017 Dec 1.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

[This corrects the article on p. 426 in vol. 8, PMID: 28955291.].
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http://dx.doi.org/10.3389/fneur.2017.00642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716986PMC
December 2017

A Description of a New Continuous Physiological Index in Traumatic Brain Injury Using the Correlation between Pulse Amplitude of Intracranial Pressure and Cerebral Perfusion Pressure.

J Neurotrauma 2018 Apr 9;35(7):963-974. Epub 2018 Feb 9.

Brain Physics Laboratory, Division of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.

To describe a new continuous index of physiologic measurement in a traumatic brain injury (TBI) population, the moving correlation coefficient between intracranial pressure (ICP) pulse amplitude (AMP) and cerebral perfusion pressure (CPP), which we refer to as RAC. We use patient examples of sustained intracranial hypertension, systemic arterial hypotension, and plateau waves, as well as the retrospective analysis of 358 non-decompressive craniectomy (DC) TBI patients with high-frequency ICP and arterial blood pressure data, to explore the relationships of this new index, RAC, with AMP, ICP, CPP, RAP (correlation coefficient between AMP and ICP), pressure reactivity index (PRx), and pulse amplitude index (PAx). We compared the RAC-CPP relationship to that observed between CPP and both PRx and PAx. RAC displays temporal responsiveness to sustained increased ICP, arterial hypotension, and plateau waves, with positive values found during episodes of high ICP and low CPP. Analysis of AMP versus CPP and AMP versus ICP relationships in data from the entire non-DC cohort show lower breakpoints for AMP/CPP at CPP = 40 mm Hg and upper breakpoints for AMP/ICP at ICP = 50-60 mm Hg. RAC trends to positive values with increasing ICP, particularly with ICP values above the peak in AMP (ICP >50 mm Hg), though its interpretation requires concomitant interpretation of AMP, RAP, and PRx/PAx to determine contributions of compensatory reserve and cerebrovascular responsiveness to the changes observed in RAC. There is a parabolic relationship between RAC versus CPP, with trends toward positive RAC values near (and beyond) limits for low and high CPPs, suggesting that RAC may be used in the determination of optimum CPP. RAC appears to carry information regarding both cerebrovascular responsiveness and cerebral compensatory reserve. This contributes to RAC's uniqueness and complex interpretation. Further prospective, clinical studies of RAC in CPP optimum estimation and outcome prediction in TBI are required.
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http://dx.doi.org/10.1089/neu.2017.5241DOI Listing
April 2018

The British Neurosurgical Trainee Research Collaborative: Five years on.

Acta Neurochir (Wien) 2018 Jan 4;160(1):23-28. Epub 2017 Nov 4.

Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital and University of Cambridge, Cambridge, CB2 0QQ, UK.

Since its inception in 2012, the British Neurosurgical Trainee Research Collaborative (BNTRC) has established itself as a robust example of a trainee-led research collaborative. This article summarises the work of the collaborative over its first 5 years of existence, outlining the structure, its research projects, impact and future directions.
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http://dx.doi.org/10.1007/s00701-017-3351-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735202PMC
January 2018

A systematic review of cerebral microdialysis and outcomes in TBI: relationships to patient functional outcome, neurophysiologic measures, and tissue outcome.

Acta Neurochir (Wien) 2017 12 7;159(12):2245-2273. Epub 2017 Oct 7.

Department of Anesthesia, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

Objective: To perform a systematic review on commonly measured cerebral microdialysis (CMD) analytes and their association to: (A) patient functional outcome, (B) neurophysiologic measures, and (C) tissue outcome; after moderate/severe TBI. The aim was to provide a foundation for next-generation CMD studies and build on existing pragmatic expert guidelines for CMD.

Methods: We searched MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016). Strength of evidence was adjudicated using GRADE.

Results: (A) Functional Outcome: 55 articles were included, assessing outcome as mortality or Glasgow Outcome Scale (GOS) at 3-6 months post-injury. Overall, there is GRADE C evidence to support an association between CMD glucose, glutamate, glycerol, lactate, and LPR to patient outcome at 3-6 months. (B) Neurophysiologic Measures: 59 articles were included. Overall, there currently exists GRADE C level of evidence supporting an association between elevated CMD measured mean LPR, glutamate and glycerol with elevated ICP and/or decreased CPP. In addition, there currently exists GRADE C evidence to support an association between elevated mean lactate:pyruvate ratio (LPR) and low PbtO. Remaining CMD measures and physiologic outcomes displayed GRADE D or no evidence to support a relationship. (C) Tissue Outcome: four studies were included. Given the conflicting literature, the only conclusion that can be drawn is acute/subacute phase elevation of CMD measured LPR is associated with frontal lobe atrophy at 6 months.

Conclusions: This systematic review replicates previously documented relationships between CMD and various outcome, which have driven clinical application of the technique. Evidence assessments do not address the application of CMD for exploring pathophysiology or titrating therapy in individual patients, and do not account for the modulatory effect of therapy on outcome, triggered at different CMD thresholds in individual centers. Our findings support clinical application of CMD and refinement of existing guidelines.
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http://dx.doi.org/10.1007/s00701-017-3338-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686263PMC
December 2017

Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications.

Front Neurol 2017 12;8:426. Epub 2017 Sep 12.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Traumatic brain injury (TBI) triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO arising from ischemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. magnetic resonance spectroscopy (MRS) allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with "spin," e.g., H, P, and C, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin-spin interactions (J-coupling). The most commonly used clinical MRS technique, H MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include -acetylaspartate (NAA), creatine, and choline. NAA, a marker of neuronal mitochondrial activity related to adenosine triphosphate (ATP), is reported to be lower in patients with TBI than healthy controls, and the ratio of NAA/creatine at early time points may correlate with clinical outcome. H MRS acquired with shorter echo times produces a more complex spectrum, allowing detection of a wider range of metabolites. P MRS detects high-energy phosphate species, which are the end products of cellular respiration: ATP and phosphocreatine (PCr). ATP is the principal form of chemical energy in living organisms, and PCr is regarded as a readily mobilized reserve for its replenishment during periods of high utilization. The ratios of high-energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain. In addition, the chemical shift difference between inorganic phosphate and PCr enables calculation of intracellular pH. C MRS detects the C isotope of carbon in brain metabolites. As the natural abundance of C is low (1.1%), C MRS is typically performed following administration of C-enriched substrates, which permits tracking of the metabolic fate of the infused C in the brain over time, and calculation of metabolic rates in a range of biochemical pathways, including glycolysis, the tricarboxylic acid cycle, and glutamate-glutamine cycling. The advent of new hyperpolarization techniques to transiently boost signal in C-enriched MRS studies shows promise in this field, and further developments are expected.
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http://dx.doi.org/10.3389/fneur.2017.00426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600917PMC
September 2017

Monitoring the Neuroinflammatory Response Following Acute Brain Injury.

Front Neurol 2017 20;8:351. Epub 2017 Jul 20.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are major contributors to morbidity and mortality. Following the initial insult, patients may deteriorate due to secondary brain damage. The underlying molecular and cellular cascades incorporate components of the innate immune system. There are different approaches to assess and monitor cerebral inflammation in the neuro intensive care unit. The aim of this narrative review is to describe techniques to monitor inflammatory activity in patients with TBI and SAH in the acute setting. The analysis of pro- and anti-inflammatory cytokines in compartments of the central nervous system (CNS), including the cerebrospinal fluid and the extracellular fluid, represent the most common approaches to monitor surrogate markers of cerebral inflammatory activity. Each of these compartments has a distinct biology that reflects local processes and the cross-talk between systemic and CNS inflammation. Cytokines have been correlated to outcomes as well as ongoing, secondary injury progression. Alongside the dynamic, focal assay of humoral mediators, imaging, through positron emission tomography, can provide a global measurement of inflammatory cell activity, which reveals long-lasting processes following the initial injury. Compared to the innate immune system activated acutely after brain injury, the adaptive immune system is likely to play a greater role in the chronic phase as evidenced by T-cell-mediated autoreactivity toward brain-specific proteins. The most difficult aspect of assessing neuroinflammation is to determine whether the processes monitored are harmful or beneficial to the brain as accumulating data indicate a dual role for these inflammatory cascades following injury. In summary, the inflammatory component of the complex injury cascade following brain injury may be monitored using different modalities. Using a multimodal monitoring approach can potentially aid in the development of therapeutics targeting different aspects of the inflammatory cascade and improve the outcome following TBI and SAH.
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http://dx.doi.org/10.3389/fneur.2017.00351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517395PMC
July 2017

Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: A prospective observational study.

PLoS Med 2017 Jul 25;14(7):e1002356. Epub 2017 Jul 25.

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.

Background: The invasive nature of the current methods for monitoring of intracranial pressure (ICP) has prevented their use in many clinical situations. Several attempts have been made to develop methods to monitor ICP non-invasively. The aim of this study is to assess the relationship between ultrasound-based non-invasive ICP (nICP) and invasive ICP measurement in neurocritical care patients.

Methods And Findings: This was a prospective, single-cohort observational study of patients admitted to a tertiary neurocritical care unit. Patients with brain injury requiring invasive ICP monitoring were considered for inclusion. nICP was assessed using optic nerve sheath diameter (ONSD), venous transcranial Doppler (vTCD) of straight sinus systolic flow velocity (FVsv), and methods derived from arterial transcranial Doppler (aTCD) on the middle cerebral artery (MCA): MCA pulsatility index (PIa) and an estimator based on diastolic flow velocity (FVd). A total of 445 ultrasound examinations from 64 patients performed from 1 January to 1 November 2016 were included. The median age of the patients was 53 years (range 37-64). Median Glasgow Coma Scale at admission was 7 (range 3-14), and median Glasgow Outcome Scale was 3 (range 1-5). The mortality rate was 20%. ONSD and FVsv demonstrated the strongest correlation with ICP (R = 0.76 for ONSD versus ICP; R = 0.72 for FVsv versus ICP), whereas PIa and the estimator based on FVd did not correlate with ICP significantly. Combining the 2 strongest nICP predictors (ONSD and FVsv) resulted in an even stronger correlation with ICP (R = 0.80). The ability to detect intracranial hypertension (ICP ≥ 20 mm Hg) was highest for ONSD (area under the curve [AUC] 0.91, 95% CI 0.88-0.95). The combination of ONSD and FVsv methods showed a statistically significant improvement of AUC values compared with the ONSD method alone (0.93, 95% CI 0.90-0.97, p = 0.01). Major limitations are the heterogeneity and small number of patients included in this study, the need for specialised training to perform and interpret the ultrasound tests, and the variability in performance among different ultrasound operators.

Conclusions: Of the studied ultrasound nICP methods, ONSD is the best estimator of ICP. The novel combination of ONSD ultrasonography and vTCD of the straight sinus is a promising and easily available technique for identifying critically ill patients with intracranial hypertension.
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http://dx.doi.org/10.1371/journal.pmed.1002356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526499PMC
July 2017

Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction.

Sci Rep 2017 04 21;7(1):1003. Epub 2017 Apr 21.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167, Cambridge Biomedical Campus, CB2 0QQ, UK.

Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients' brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI.
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http://dx.doi.org/10.1038/s41598-017-01149-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430749PMC
April 2017

Improved long-term survival with subdural drains following evacuation of chronic subdural haematoma.

Acta Neurochir (Wien) 2017 05 27;159(5):903-905. Epub 2017 Mar 27.

Division of Neurosurgery, Addenbrooke's Hospital, Box 167, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

Background: Chronic subdural haematoma (CSDH) is a common condition that is effectively managed by burrhole drainage but requires repeat surgery in a significant minority of patients. The Cambridge Chronic Subdural Haematoma Trial (CCSHT) was a randomised controlled study that showed placement of subdural drains for 48 h following burrhole evacuation significantly reduces the incidence of reoperation and improves survival at 6 months. The present study examined the long-term survival of the patients in the trial.

Methods: In the original trial patients at a single neurosurgical centre from 2004-2007 were randomly assigned to receive a drain (n = 108) or no drain (n = 107) following burrhole drainage of CSDH. We ascertained whether the trial patients were alive in February 2016-a minimum of 8 years following enrollment-via the UK NHS tracing service. Survival was compared between the trial groups and against expected survival for the UK general population matched for age and sex.

Results: At 5 years following surgery the drain group continued to have significantly better survival than the no drain patients (p = 0.027), but this was no longer apparent at 10 years. Survival of patients in the drain group did not differ significantly from that of the general population whereas patients who did not receive a drain had significantly lower survival than expected (p = 0.0006).

Conclusion: Subdural drains following CSDH evacuation are associated with improved long-term survival, which appears similar to that expected for the general population of the same age and sex. All patients having burrhole CSDH evacuation should receive a drain as standard practice unless specifically contraindicated.
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http://dx.doi.org/10.1007/s00701-017-3095-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385189PMC
May 2017

Tests of Eustachian Tube Function: the Effect of Testing Technique on Tube Opening in Healthy Ears.

Otol Neurotol 2017 06;38(5):714-720

*Addenbrooke's Hospital, University of Cambridge †Clinical School, University of Cambridge, Cambridge, UK.

Objective: There is no agreement on the best clinical test for Eustachian tube (ET) dysfunction. Numerous tests have been developed to detect ET opening, and all require a patient to perform a Valsalva, Toynbee or sniff maneuver, or to swallow on demand. We aimed to characterize existing tests of ET function in healthy ears, and identify the optimal method and patient maneuver for each test. Our own normative data is presented alongside published comparisons.

Study Design: Diagnostic test cohort study.

Setting: Tertiary referral center.

Patients: Seventy-five healthy ears from 42 volunteers.

Interventions: Six tests of ET function, each performed using multiple different patient maneuvers.

Main Outcome Measure: Detected ET opening rate for each test-maneuver combination.

Results: The highest detected opening rates were: Sonotubometry 94%; nine-step test inflation/deflation 93/94%; continuous impedance 88%, patient-reported opening 79%; observed tympanic membrane movement 78%; and Tubo-tympano-aerodynamic-graphy 76%. Valsalva maneuvers were most effective at opening the ET. Toynbee and swallow maneuvers were more effective when performed without water, when compared to with water. For Valsalva and sniff maneuvers, there was significant correlation between the peak nasopharyngeal pressure generated and the ET opening rate.

Conclusion: Based on ET opening detection rates, we recommend the use of dry swallows with sonotubometry and the nine-step test. When testing patient-reported opening and observed membrane movement, and when performing Tubo-tympano-aerodynamic-graphy and impedance tests, we recommend the use of Valsalva maneuvers. Further studies are required to explore the association between the test technique and results in ears with ET dysfunction.
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http://dx.doi.org/10.1097/MAO.0000000000001375DOI Listing
June 2017

The reporting of study and population characteristics in degenerative cervical myelopathy: A systematic review.

PLoS One 2017 1;12(3):e0172564. Epub 2017 Mar 1.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Object: Degenerative cervical myelopathy [DCM] is a disabling and increasingly prevalent condition. Variable reporting in interventional trials of study design and sample characteristics limits the interpretation of pooled outcomes. This is pertinent in DCM where baseline characteristics are known to influence outcome. The present study aims to assess the reporting of the study design and baseline characteristics in DCM as the premise for the development of a standardised reporting set.

Methods: A systematic review of MEDLINE and EMBASE databases, registered with PROSPERO (CRD42015025497) was conducted in accordance with PRISMA guidelines. Full text articles in English, with >50 patients (prospective) or >200 patients (retrospective), reporting outcomes of DCM were deemed to be eligible.

Results: A total of 108 studies involving 23,876 patients, conducted world-wide, were identified. 33 (31%) specified a clear primary objective. Study populations often included radiculopathy (51, 47%) but excluded patients who had undergone previous surgery (42, 39%). Diagnositic criteria for myelopathy were often uncertain; MRI assessment was specified in only 67 (62%) of studies. Patient comorbidities were referenced by 37 (34%) studies. Symptom duration was reported by 46 (43%) studies. Multivariate analysis was used to control for baseline characteristics in 33 (31%) of studies.

Conclusions: The reporting of study design and sample characteristics is variable. The development of a consensus minimum dataset for (CODE-DCM) will facilitate future research synthesis in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172564PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332071PMC
August 2017