Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

A proposed novel traumatic brain injury classification system - an overview and inter-rater reliability validation on behalf of the Society of British Neurological Surgeons.

INTRODUCTION: The measurement of traumatic brain injury (TBI) 'severity' has traditionally been based on the earliest Glasgow Coma Score (GCS) recorded, however, the underlying parenchymal pathology is highly heterogonous. This heterogeneity renders prediction of outcome on an individual patient level inaccurate and makes comparison between patients both in clinical practice and research difficult. The complexity of this heterogeneity has resulted in generic all encompassing 'traumatic brain injury protocols'. Early management and studies of neuro-protectants are often done irrespective of TBI type, yet it may well be that a specific treatment may be beneficial in a subset of TBI pathologies. METHODS: A simple CT-based classification system rating the recognised types of blunt TBI (extradural, subdural, subarachnoid haemorrhage, contusions/intracerebral haematoma and diffuse axonal injury) as mild (1), moderate (2) or severe (3) is proposed. Hypoxic brain injury, a common secondary injury following TBI, is also included. Scores can be combined to reflect concomitant types of TBI and predominant location of injury is also recorded. To assess interrater reliability, 50 patient CT images were assessed by 5 independent clinicians of varying experience. Interrater reliability was calculated using overall agreement through Cronbach's alpha including confidence intervals for intra-class coefficients. RESULTS: Interrater reliability scores showed strong agreement for same score and same injury for TBIs with blood on CT and Cronbach's alpha co-efficient (range 0.87-0.93) demonstrated excellent correlation between raters. Cronbach's alpha was not affected when individual raters were removed. CONCLUSIONS: The proposed simple CT classification system has good inter-rater reliability and hence potentially could enable better individual prognostication and targeted treatments to be compared while also accounting for multiple intracranial injury types. Further studies are proposed and underway.

Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension.

BACKGROUND: The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. METHODS: From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. RESULTS: The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). CONCLUSIONS: At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).

Pharmacological management of post-traumatic seizures in adults: current practice patterns in the UK and the Republic of Ireland.

BACKGROUND: Patient selection for seizure prophylaxis after traumatic brain injury (TBI) and duration of anti-epileptic drug treatment for patients with early post-traumatic seizures (PTS), remain plagued with uncertainty. In early 2017, a collaborative group of neurosurgeons, neurologists, neurointensive care and rehabilitation medicine physicians was formed in the UK with the aim of assessing variability in current practice and gauging the degree of uncertainty to inform the design of future studies. Here we present the results of a survey of clinicians managing patients with TBI in the UK and Ireland. MATERIALS AND METHODS: An online survey was developed and piloted. Following approval by the Academic Committee of the Society of British Neurological Surgeons, it was distributed via appropriate electronic mailing lists. RESULTS: One hundred and seventeen respondents answered the questionnaire, predominantly neurosurgeons (76%) from 30 (of 32) trauma-receiving hospitals in the UK and Ireland. Fifty-three percent of respondents do not routinely use seizure prophylaxis, but 38% prescribe prophylaxis for one week. Sixty percent feel there is uncertainty regarding the use of seizure prophylaxis, and 71% would participate in further research to address this question. Sixty-two percent of respondents use levetiracetam for treatment of seizures during the acute phase, and 42% continued for a total of 3 months. Overall, 90% were uncertain about the duration of treatment for seizures, and 78% would participate in further research to address this question. CONCLUSION: The survey results demonstrate the variation in practice and uncertainty in both described aspects of management of patients who have suffered a TBI. The majority of respondents would want to participate in future research to help try and address this critical issue, and this shows the importance and relevance of these two clinical questions.

Consensus statement from the International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury : Consensus statement.

BACKGROUND: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries. RESULTS: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval. CONCLUSIONS: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

Mountain neurology.

Mountain climbers may develop specific illnesses that largely depend on the altitude reached and the rate of ascent. The popularity of travel to high altitude destinations, extreme tourist activities and mountain climbing means that neurologists in low-altitude countries are increasingly likely to encounter neurological problems and disorders in people exposed to high altitude. Additionally, they may have to advise patients with pre-existing neurological conditions on the risks of ascent to altitude. This article focuses on neurological-related high-altitude illnesses: acute mountain sickness and high-altitude cerebral oedema, as well as high-altitude retinopathy and other neurological disorders. This overview combines current understood pathogenesis with the experience of managing altitude-related illness at the foot of Mount Kilimanjaro in northern Tanzania, the tallest free-standing mountain in the world.

Epidemiology of Pediatric Traumatic Brain Injury in a Dense Urban Area Served by a Helicopter Trauma Service.

OBJECTIVE: Pediatric traumatic brain injury is the most common cause of death and a major cause of morbidity in children and young adults worldwide. Despite this, our understanding of epidemiological factors relating to this type of injury is incomplete. The objective of this study was to explore a variety of factors relating to these injuries including mechanism, timing of emergency response, prehospital management, radiological diagnosis, neurosurgical care, and final outcomes. METHODS: A retrospective review of all pediatric traumas attending a single large, densely populated urban area within a 2-year period was undertaken, and all cases with significant pediatric traumatic brain injury, as defined by a computed tomography scan showing an intracranial injury, were included for further analysis. Various epidemiological and treatment factors were explored. RESULTS: One hundred sixteen patients fulfilled the inclusion criteria, and their injuries and management were explored further. A variety of key trends were identified. The most common mechanism of injury was pedestrian struck by car followed by falls from height. Males were injured 5 times more frequently than girls. A helicopter emergency trauma team attended 22% of the patients and intubated 11 in total. The most common intracranial injuries were skull fractures followed by contusions. Nineteen neurosurgical interventions were undertaken. Overall mortality in all patients was 8%. CONCLUSIONS: An improved understanding of the epidemiology of pediatric brain injury will provide baselines for future outcome measurement and comparative analysis. This may improve service organization and delivery.

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia.

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

Near-infrared spectroscopy (NIRS) to detect traumatic intracranial haematoma: A systematic review and meta-analysis.

OBJECTIVES AND METHODS: Head injury is the most common trauma presentation to UK emergency departments, with around 1.2 million patients each year. The key management principal for this time critical illness remains early surgical intervention. With the development of handheld near-infrared spectroscopy (NIRS) devices, there is now the possibility of triaging and diagnosing these patients immediately, where computed tomography (CT) scanner is unavailable. NIRS has two related but distinct potential uses within clinical medicine. Firstly, as a triage tool both in hospital and prehospital settings by doctors, nurses or paramedics as determined by its negative predictive value (NPV). Secondly, as a diagnostic aid as determined by its positive predictive value (PPV). The aim of this systematic review and meta-analysis is therefore to interrogate the current literature on NIRS in detecting intracranial haematomas. RESULTS: NIRS technology has a cross-study sensitivity of 78%, specificity of 90%, PPV of 77%, and a NPV of 90%, which does not meet current standards as a diagnostic/triage tool in the populations studied. Additionally, its use is limited to those without extracranial injuries and may also be complicated by long scan times. CONCLUSION: Larger and more heterogeneous studies are required for specifically evaluating NIRS performance in detecting intracranial lesions requiring emergency evacuation.

Extreme, expedition, and wilderness medicine.

Extreme, expedition, and wilderness medicine are modern and rapidly evolving specialties that address the spirit of adventure and exploration. The relevance of and interest in these specialties are changing rapidly to match the underlying activities, which include global exploration, adventure travel, and military deployments. Extreme, expedition, and wilderness medicine share themes of providing best available medical care in the outdoors, especially in austere or remote settings. Early clinical and logistics decision making can often have important effects on subsequent outcomes. There are lessons to be learned from out-of-hospital care, military medicine, humanitarian medicine, and disaster medicine that can inform in-hospital medicine, and vice-versa. The future of extreme, expedition, and wilderness medicine will be defined by both recipients and practitioners, and empirical observations will be transformed by evidence-based practice.

Pre-hospital emergency medicine.

Pre-hospital care is emergency medical care given to patients before arrival in hospital after activation of emergency medical services. It traditionally incorporated a breadth of care from bystander resuscitation to statutory emergency medical services treatment and transfer. New concepts of care including community paramedicine, novel roles such as emergency care practitioners, and physician delivered pre-hospital emergency medicine are re-defining the scope of pre-hospital care. For severely ill or injured patients, acting quickly in the pre-hospital period is crucial with decisions and interventions greatly affecting outcomes. The transfer of skills and procedures from hospital care to pre-hospital medicine enables early advanced care across a range of disciplines. The variety of possible pathologies, challenges of environmental factors, and hazardous situations requires management that is tailored to the patient's clinical need and setting. Pre-hospital clinicians should be generalists with a broad understanding of medical, surgical, and trauma pathologies, who will often work from locally developed standard operating procedures, but who are able to revert to core principles. Pre-hospital emergency medicine consists of not only clinical care, but also logistics, rescue competencies, and scene management skills (especially in major incidents, which have their own set of management principles). Traditionally, research into the hyper-acute phase (the first hour) of disease has been difficult, largely because physicians are rarely present and issues of consent, transport expediency, and resourcing of research. However, the pre-hospital phase is acknowledged as a crucial period, when irreversible pathology and secondary injury to neuronal and cardiac tissue can be prevented. The development of pre-hospital emergency medicine into a sub-specialty in its own right should bring focus to this period of care.

Prognosis of patients with bilateral fixed dilated pupils secondary to traumatic extradural or subdural haematoma who undergo surgery: a systematic review and meta-analysis.

PRIMARY OBJECTIVE: To review the prognosis of patients with bilateral fixed and dilated pupils secondary to traumatic extradural (epidural) or subdural haematoma who undergo surgery. METHODS: A systematic review and meta-analysis was performed using random effects models. The Cochrane Central Register of Controlled Trials and PubMed databases were searched to identify relevant publications. Eligible studies were publications that featured patients with bilateral fixed and dilated pupils who underwent surgical evacuation of traumatic extra-axial haematoma, and reported on the rate of favourable outcome (Glasgow Outcome Score 4 or 5). RESULTS: Five cohort studies met the inclusion criteria, collectively reporting the outcome of 82 patients. In patients with extradural haematoma, the mortality rate was 29.7% (95% CI 14.7% to 47.2%) with a favourable outcome seen in 54.3% (95% CI 36.3% to 71.8%). In patients with acute subdural haematoma, the mortality rate was 66.4% (95% CI 50.5% to 81.9%) with a favourable outcome seen in 6.6% (95% CI 1.8% to 14.1%). CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Despite the poor overall prognosis of patients with closed head injury and bilateral fixed and dilated pupils, our findings suggest that a good recovery is possible if an aggressive surgical approach is taken in selected cases, particularly those with extradural haematoma. TRIAL REGISTRATION NUMBER: CRD42013005198.

Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

OBJECTIVE: Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. METHODS: Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. RESULTS: Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). CONCLUSIONS: An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution.

Cerebral venous system and anatomical predisposition to high-altitude headache.

OBJECTIVE: As inspired oxygen availability falls with ascent to altitude, some individuals develop high-altitude headache (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies. METHODS: In high-altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea-level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores [0-4]≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea-level hypoxic study, 11 subjects underwent gadolinium-enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen=0.11, 1 hour). RESULTS: In the high-altitude studies, headache burden correlated with both RVD (Spearman rho=0.55, p=0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r=-0.56, p=0.03). It also related inversely to both the lateral+third ventricle summed volumes (Spearman rho=-0.5, p=0.05) and pericerebellar CSF volume (r=-0.56, p=0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r=-0.66, p<0.05 and r=-0.75, p<0.05, respectively). INTERPRETATION: Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur.

Management of malignant middle cerebral artery infarction following a cardiac stab wound--the role of early decompressive craniectomy.

We report the presentation, investigation and management of a 22-year-old male who developed a right malignant middle cerebral artery infarct following a cardiac stab wound. This case exemplifies that early identification and timely decompression of young patients with embolic infarcts as a result of penetrating trauma can lead to a favourable clinical outcome.

Proposal for establishment of the UK Cranial Reconstruction Registry (UKCRR).

BACKGROUND: The increasing utilisation of decompressive craniectomy for traumatic brain injury and stroke has led to an increase in the number of cranioplasties undertaken. Cranioplasty is also undertaken following excision of tumours originating from or invading the skull vault, removal of bone flaps due to post-operative infection, and decompressive craniectomy for the management of rarer causes of brain oedema and/or refractory intracranial hypertension. The existing literature which mainly consists of single-centre, retrospective studies, shows a significant variation in practice patterns and a wide range of morbidity. There also exists a need to measure the outcome as perceived by the patients themselves with patient reported outcome measures (PROMs; functional outcome, quality of life, satisfaction with cosmesis). In the UK, the concept of long-term surveillance of neurosurgical implants is well established with the UK shunt registry. Based on this background, we propose to establish the UK Cranial Reconstruction Registry (UKCRR). AIM: The overarching aim of the UKCRR is to collect high-quality data about cranioplasties undertaken across the UK and Ireland in order to improve outcomes for patients. METHODS: Any patient undergoing reconstruction of the skull vault with autologous bone, titanium, or synthetic material in participating units will be eligible for inclusion. Data will be submitted directly by participating units to the Outcome Registry Intervention and Operation Network secure platform. A Steering Committee will be responsible for overseeing the strategic direction and running of the UKCRR. OUTCOME MEASURES: These will include re-operation due to a cranioplasty-related issue, surgical site infection, re-admission due to a cranioplasty-related issue, unplanned post-operative escalation of care, adverse events, length of stay in admitting unit, destination at discharge from admitting unit, mortality at discharge from admitting unit, neurological status and PROMs during routine follow-up. CONCLUSION: The UKCRR will be an important pillar in the ongoing efforts to optimise the outcomes of patients undergoing cranioplasty.

Cervical spine immobilisation following blunt trauma in pre-hospital and emergency care: A systematic review.

OBJECTIVES: To assess whether different cervical spine immobilisation strategies (full immobilisation, movement minimisation or no immobilisation), impact neurological and/or other outcomes for patients with suspected cervical spinal injury in the pre-hospital and emergency department setting. DESIGN: Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library and two research registers were searched until September 2023. ELIGIBILITY CRITERIA: All comparative studies (prospective or retrospective) that examined the potential benefits and/or harms of immobilisation practices during pre-hospital and emergency care of patients with a potential cervical spine injury (pre-imaging) following blunt trauma. DATA EXTRACTION AND SYNTHESIS: Two authors independently selected and extracted data. Risk of bias was appraised using the Cochrane ROBINS-I tool for non-randomised studies. Data were synthesised without meta-analysis. RESULTS: Six observational studies met the inclusion criteria. The methodological quality was variable, with most studies having serious or critical risk of bias. The effect of cervical spine immobilisation practices such as full immobilisation or movement minimisation during pre-hospital and emergency care did not show clear evidence of benefit for the prevention of neurological deterioration, spinal injuries and death compared with no immobilisation. However, increased pain, discomfort and anatomical complications were associated with collar application during immobilisation. CONCLUSIONS: Despite the limited evidence, weak designs and limited generalisability, the available data suggest that pre-hospital cervical spine immobilisation (full immobilisation or movement minimisation) was of uncertain value due to the lack of demonstrable benefit and may lead to potential complications and adverse outcomes. High-quality randomised comparative studies are required to address this important question. TRIAL REGISTRATION: PROSPERO REGISTRATION Fiona Lecky, Abdullah Pandor, Munira Essat, Anthea Sutton, Carl Marincowitz, Gordon Fuller, Stuart Reid, Jason Smith. A systematic review of cervical spine immobilisation following blunt trauma in pre-hospital and emergency care. PROSPERO 2022 CRD42022349600 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022349600.

Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.

Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent. We assessed diffusion of the small magnetic resonance (MR)-detectible molecule gadobutrol from microdialysis catheters in six subjects (complete data five subjects, incomplete data one subject) who had sustained a severe TBI. Diffusion pattern and distance in cerebral white matter were assessed using T1 (time for MR spin-lattice relaxation) maps at 1 mm isotropic resolution in a 3 Tesla MR scanner. Gadobutrol at 10 mmol/L diffused from cerebral microdialysis catheters in a uniform spheroidal (ellipsoid of revolution) pattern around the catheters' semipermeable membranes, and across gray matter-white matter boundaries. Evidence of gadobutrol diffusion was found up to a mean of 13.4 ± 0.5 mm (mean ± standard deviation [SD]) from catheters, but with a steep concentration drop off so that ≤50% of maximum concentration was achieved at ∼4 mm, and ≤10% of maximum was found beyond ∼7 mm from the catheters. There was little variation between subjects. The relaxivity of gadobutrol in human cerebral white matter was estimated to be 1.61 ± 0.38 L.mmol-1sec-1 (mean ± SD); assuming gadobutrol remained extracellular thereby occupying 20% of total tissue volume (interstitium), and concentration equilibrium with perfusion fluid was achieved immediately adjacent to catheters after 24 h of perfusion. No statistically significant change was found in the concentration of the extracellular metabolites glucose, lactate, pyruvate, nor the lactate/pyruvate ratio during gadobutrol perfusion when compared with period of baseline microdialysis perfusion. Cerebral microdialysis allows continuous monitoring of regional cerebral metabolism-the volume of which is now clearer from this study. It also has the potential to deliver small molecule therapies to focal pathologies of the human brain. This study provides a platform for future development of new catheters optimally designed to treat such conditions.