Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics (STARSHIP): protocol to study cerebral autoregulation in a prospective multicentre observational research database study.

INTRODUCTION: Studying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management. Experience in paediatric TBI (PTBI) is limited to single-centre studies despite disproportionately higher incidence of morbidity and mortality in PTBI than in adult TBI. PROJECT: We describe the protocol to study cerebral autoregulation using PRx in PTBI. The project called Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics is a multicentre prospective ethics approved research database study from 10 centres across the UK. Recruitment started in July 2018 with financial support from local/national charities (Action Medical Research for Children, UK). METHODS AND ANALYSIS: The first phase of the project is powered to detect optimal thresholds of PRx associated with favourable outcome in PTBI by recruiting 135 patients (initial target of 3 years which has changed to 5 years due to delays related to COVID-19 pandemic) from 10 centres in the UK with outcome follow-up to 1-year postictus. The secondary objectives are to characterise patterns of optimal cerebral perfusion pressure in PTBI and compare the fluctuations in these measured parameters with outcome. The goal is to create a comprehensive research database of a basic set of high-resolution (full waveforms resolution) neuromonitoring data in PTBI for scientific use. ETHICS AND DISSEMINATION: Favourable ethical approval has been provided by Health Research Authority, Southwest-Central Bristol Research Ethics Committee (Ref: 18/SW/0053). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05688462.

Sagittal sinus thrombosis with subarachnoid haemorrhage in a patient with COVID-19 infection.

A man in his late 50s was admitted with a 10-day history of right frontotemporal headache, left arm and leg weakness, and a sudden decline in visual acuity in the right eye. The patient had recent exposure to COVID-19 infection and tested positive for the same on admission. A CT scan of the head done on arrival demonstrated a subarachnoid haemorrhage in the right central sulcus with an underlying superior sagittal sinus thrombosis. No other known risk factors for central venous sinus thrombosis could be identified. The patient had a normal level of consciousness on admission clinically; however, he was in severe pain. A collective decision was made to administer anticoagulants to the patient with heparin after carefully deliberating the risk-to-benefit ratio of a superior sagittal thrombus with an associated subarachnoid haemorrhage. Our patient recovered and was discharged after 2 weeks on warfarin. We present this case to highlight the potential risks of hypercoagulable and neurotropic complications of COVID-19 infections, with special emphasis on cerebral venous thrombosis.

Concussion in Non-athletes: Assessment of Cognition and Symptomatology (CONTACTS) study protocol - an exploratory cohort study investigating the utility of sports concussion assessment tools and salivary microRNAs to diagnose concussion in NHS patients.

INTRODUCTION: Concussion is a complex pathophysiological process with a wide range of non-specific signs and symptoms. There are currently no objective diagnostic tests to identify concussion, and diagnosis relies solely on history and examination. Recent research has identified a unique panel of microRNAs (miRNAs) that distinguish between concussed and non-concussed rugby players. This study aims to assess the diagnostic utility of salivary miRNAs in concussion for a sample of UK National Health Service patients and whether well-established sports-related concussion (SRC) assessment tools may be translated into the emergency department (ED). METHODS AND ANALYSIS: Concussion in Non-athletes: Assessment of Cognition and Symptomatology is a single-centre, prospective, two-phase cohort study. The concussed cohort will consist of participants with maxillofacial trauma and concurrent concussion. The control cohort will consist of participants with isolated limb trauma and no evidence of concussion. Participants will be recruited in the ED and saliva samples will be taken to identify the presence of miRNAs. The SRC assessments being investigated include the Sports Concussion Assessment Test, Fifth Edition (SCAT5), the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and the ImPACT Quick. Follow-up will be at 24-48 hours in-hospital and remotely via telephone and email at 14 days and 6 months. ETHICS AND DISSEMINATION: Ethical approval was granted in February 2021 by the West Midlands Coventry & Warwickshire Research Ethics Committee (ref 20/WM/0299). The investigators intend to submit their study findings for publication in peer-reviewed journals and to disseminate study findings via presentation at academic meetings. The results will also form part of a doctorate thesis, registered at the University of Birmingham.

Qualitative study exploring factors affecting the implementation of a vocational rehabilitation intervention in the UK major trauma pathway.

OBJECTIVES: This study aimed to: (1) understand the context for delivering a trauma vocational rehabilitation (VR) intervention; (2) identify potential barriers and enablers to the implementation of a VR intervention post-trauma. DESIGN: Qualitative study. Data were collected in person or via phone using different methods: 38 semistructured interviews, 11 informal 'walk-through care pathways' interviews, 5 focus groups (n=25), 5 codesign workshops (n=43). Data were thematically analysed using the framework approach, informed by the Consolidated Framework for Implementation Research. SETTING: Stakeholders recruited across five UK major trauma networks. PARTICIPANTS: A variety of stakeholders were recruited (n=117) including trauma survivors, rehabilitation physicians, therapists, psychologists, trauma coordinators and general practitioners. We recruited 32 service users (trauma survivors or carers) and 85 service providers. RESULTS: There were several issues associated with implementing a trauma VR intervention including: culture within healthcare/employing organisations; extent to which healthcare systems were networked with other organisations; poor transition between different organisations; failure to recognise VR as a priority; external policies and funding. Some barriers were typical implementation issues (eg, funding, policies, openness to change). This study further highlighted the challenges associated with implementing a complex intervention like VR (eg, inadequate networking/communication, poor service provision, perceived VR priority). Our intervention was developed to overcome these barriers through adapting a therapist training package, and by providing early contact with patient/employer, a psychological component alongside occupational therapy, case coordination/central point of contact, and support crossing sector boundaries (eg, between health/employment/welfare). CONCLUSIONS: Findings informed the implementation of our VR intervention within the complex trauma pathway. Although we understand how to embed it within this context, the success of its implementation needs to be measured as part of a process evaluation in a future trial.

Prone position plexopathy: an avoidable complication of prone positioning for COVID-19 pneumonitis?

Prone positioning is a mainstay of management for those presenting to the intensive care unit with moderate-to-severe acute respiratory distress syndrome due to COVID-19. While this is a necessary and life-saving intervention in selected patients, careful positioning and meticulous care are required to prevent compression and traction of the brachial plexus, and resultant brachial plexopathy. We describe two patients who developed a brachial plexus injury while undergoing prone positioning for management of COVID-19 pneumonitis. Both patients were diabetic and underwent prolonged periods in the prone position during which the plexopathy affected arm was abducted for 19 and 55 hours, respectively. We discuss strategies to reduce the risk of this rare but potentially disabling complication of prone positioning.

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: a nationwide study in Spain.

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.

Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study.

OBJECTIVE: To characterise the clinical course of delirium for patients with COVID-19 in the intensive care unit, including postdischarge neuropsychological outcomes. DESIGN: Retrospective chart review and prospective survey study. SETTING: Intensive care units, large academic tertiary-care centre (USA). PARTICIPANTS: Patients (n=148) with COVID-19 admitted to an intensive care unit at Michigan Medicine between 1 March 2020 and 31 May 2020 were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: Delirium was the primary outcome, assessed via validated chart review method. Secondary outcomes included measures related to delirium, such as delirium duration, antipsychotic use, length of hospital and intensive care unit stay, inflammatory markers and final disposition. Neuroimaging data were also collected. Finally, a telephone survey was conducted between 1 and 2 months after discharge to determine neuropsychological function via the following tests: Family Confusion Assessment Method, Short Blessed Test, Patient-Reported Outcomes Measurement Information System Cognitive Abilities 4a and Patient-Health Questionnaire-9. RESULTS: Delirium was identified in 108/148 (73%) patients, with median (IQR) duration lasting 10 (4-17) days. In the delirium cohort, 50% (54/108) of patients were African American and delirious patients were more likely to be female (76/108, 70%) (absolute standardised differences >0.30). Sedation regimens, inflammation, delirium prevention protocol deviations and hypoxic-ischaemic injury were likely contributing factors, and the most common disposition for delirious patients was a skilled care facility (41/108, 38%). Among patients who were delirious during hospitalisation, 4/17 (24%) later screened positive for delirium at home based on caretaker assessment, 5/22 (23%) demonstrated signs of questionable cognitive impairment or cognitive impairment consistent with dementia and 3/25 (12%) screened positive for depression within 2 months after discharge. CONCLUSION: Patients with COVID-19 commonly experience a prolonged course of delirium in the intensive care unit, likely with multiple contributing factors. Furthermore, neuropsychological impairment may persist after discharge.

Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting.

Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9-1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0-4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0-0.8%, 6/1,006]. Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.

Protocol for DexEnceph: a randomised controlled trial of dexamethasone therapy in adults with herpes simplex virus encephalitis.

INTRODUCTION: Herpes simplex virus (HSV) encephalitis is a rare severe form of brain inflammation that commonly leaves survivors and their families with devastating long-term consequences. The virus particularly targets the temporal lobe of the brain causing debilitating problems in memory, especially verbal memory. It is postulated that immunomodulation with the corticosteroid, dexamethasone, could improve outcomes by reducing brain swelling. However, there are concerns (so far not observed) that such immunosuppression might facilitate increased viral replication with resultant worsening of disease. A previous trail closed early because of slow recruitment. METHOD: DexEnceph is a pragmatic multicentre, randomised, controlled, open-label, observer-blind trial to determine whether adults with HSV encephalitis who receive dexamethasone alongside standard antiviral treatment with aciclovir for have improved clinical outcomes compared with those who receive standard treatment alone. Overall, 90 patients with HSV encephalitis are being recruited from a target of 45 recruiting sites; patients are randomised 1:1 to the dexamethasone or control arms of the study. The primary outcome measured is verbal memory as assessed by the Weschler Memory Scale fourth edition Auditory Memory Index at 26 weeks after randomisation. Secondary outcomes are measured up to 72 weeks include additional neuropsychological, clinical and functional outcomes as well as comparison of neuroimaging findings. Patient safety monitoring occurs throughout and includes the detection of HSV DNA in cerebrospinal fluid 2 weeks after randomisation, which is indicative of ongoing viral replication. Innovative methods are being used to ensure recrutiment targets are met for this rare disease. DISCUSSION: DexEnceph aims to be the first completed randomised controlled trial of corticosteroid therapy in HSV encephalitis. The results will provide evidence for future practice in managing adults with the condition and has the potential to improve outcomes . ETHICS AND DISSEMINATION: The trial has ethical approval from the UK National Research Ethics Committee (Liverpool Central, REF: 15/NW/0545, 10 August 2015). Protocol V.2.1, July 2019. The results will be published and presented as soon as possible on completion. TRIAL REGISTRATION NUMBERS: ISRCTN11774734, EUDRACT 2015-001609-16.

Personalising Outcomes after Child Cardiac Arrest (POCCA): design and recruitment challenges of a multicentre, observational study.

INTRODUCTION: Blood and imaging biomarkers show promise in prognosticating outcomes after paediatric cardiac arrest in pilot studies. We describe the methods and early recruitment challenges and solutions for an ongoing multicentre (n=14) observational trial, Personalising Outcomes following Child Cardiac Arrest to validate clinical, blood and imaging biomarkers individually and together in a clinically relevant panel. METHODS AND ANALYSIS: Children (n=164) between 48 hours and 17 years of age who receive chest compressions irrespective of provider, duration, or event location and are admitted to an intensive care unit are eligible. Blood samples will be taken on days 1-3 for the measurement of brain-focused biomarkers analysed to predict the outcome. Clinically indicated and timed brain MRI and spectroscopy biomarkers will be analysed to predict the outcome. The primary outcome for the trial is survival with favourable (Vineland Adaptive Behavioural Scale score >70) outcome at 1 year. Secondary outcomes include mortality and pre-event and postdischarge measures of emotional, cognitive, physical and family functioning and health-related quality of life. Early enrollment targets were not met due to prolonged regulatory and subcontract processes. Multiple, simultaneous interventions including modification to inclusion criteria, additional sites and site visits were implemented with successful improvement in recruitment. Study procedures including outcomes and biomarker analysis are ongoing. ETHICS AND DISSEMINATION: Twelve of 14 sites will use the centralised Institutional Review Board (IRB) at the University of Pittsburgh (PRO14030712). Two sites will use individual IRBs: Children's Healthcare of Atlanta Institutional Review Board and Children's Hospital of Wisconsin IRB. Parents and/or guardians are consented and children assented (when possible) by the site Primary investigator (PI) or research coordinator for enrollment. Study findings will be disseminated through scientific conferences, peer-reviewed journal publications, public study website materials and invited lectures. TRIAL REGISTRATION NUMBER: NCT02769026.

Brachial plexopathy as a complication of COVID-19.

COVID-19 affects a wide spectrum of organ systems. We report a 52-year-old man with hypertension and newly diagnosed diabetes mellitus who presented with hypoxic respiratory failure due to COVID-19 and developed severe brachial plexopathy. He was not treated with prone positioning respiratory therapy. Associated with the flaccid, painfully numb left upper extremity was a livedoid, purpuric rash on his left hand and forearm consistent with COVID-19-induced microangiopathy. Neuroimaging and electrophysiological data were consistent with near diffuse left brachial plexitis with selective sparing of axillary, suprascapular and pectoral fascicles. Given his microangiopathic rash, elevated D-dimers and paucifascicular plexopathy, we postulate a patchy microvascular thrombotic plexopathy. Providers should be aware of this significant and potentially under-recognised neurologic complication of COVID-19.