Publications by authors named "Jonathan Coles"

Article Synopsis
  • A chronic subdural haematoma (cSDH) is an increasingly common condition in older adults, characterized by a collection of fluid and blood in the subdural space, with no existing guidelines for optimal care from symptom onset to recovery.
  • This paper outlines the creation of consensus-based recommendations for the management of cSDH, developed by a multidisciplinary committee that included healthcare professionals, patients, and caregivers.
  • The final guideline features 67 recommendations spread across eight themes, addressing key aspects such as diagnosis, surgical procedures, non-operative management, and post-operative care despite a general lack of high-quality evidence in the literature.
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Importance: The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes.

Objective: To determine whether tissues that appear healthy on routine imaging can be investigated for selective neuronal loss using [11C]flumazenil (FMZ) positron emission tomography (PET) and to examine whether this neuronal loss is associated with long-term outcomes.

Design, Setting, And Participants: In this cross-sectional study, data were collected prospectively from 2 centers (University of Cambridge in the UK and Weill Cornell Medicine in the US) between September 1, 2004, and May 31, 2021.

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Aims And Scope: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management.

Methods: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI.

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Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism.

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A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH.

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Introduction: The epidemiology and prognosis of the isolated traumatic brain injury (TBI) and spinal cord injury (SCI) are well studied. However, the knowledge of the impact of concurrent neurotrauma is very limited.

Research Questions: To characterize the longitudinal incidence of concurrent TBI and SCI and to investigate their combined impact on clinical care and outcomes, compared to a comparative but isolated SCI or TBI.

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Background: Chronic subdural haematoma (CSDH) is increasingly common. Although treatment is triaged and provided by neurosurgery, the role of non-operative care, alongside observed peri-operative morbidity and patient complexity, suggests that optimum care requires a multi-disciplinary approach. A UK consortium (Improving Care in Elderly Neurosurgery Initiative [ICENI]) has been formed to develop the first comprehensive clinical practice guideline.

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Background: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care.

Methods: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke.

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Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls.

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Article Synopsis
  • Neurotransmitter receptors play a key role in signal transmission in the brain, but their organization and impact on brain function are not well understood.
  • Researchers created a comprehensive 3D normative atlas of 19 neurotransmitter receptors and transporters in the brains of over 1,200 healthy individuals using advanced imaging techniques.
  • The study revealed how these receptor profiles relate to brain structure, function, and even abnormalities linked with various mental disorders, paving the way for new research into brain organization and disorders.
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This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [F]-AV1451 and PET [C]PiB scans to quantify tau deposition in Braak regions II-VI and the Striatum and amyloid-β status respectively. Linear Mixed Effects models were implemented to assess how tau and amyloid-β deposition are related to change over three time points.

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Purpose Of Review: Outcome following traumatic brain injury (TBI) remains variable, and derangements in cerebral metabolism are a common finding in patients with poor outcome. This review compares our understanding of cerebral metabolism in health with derangements seen following TBI.

Recent Findings: Ischemia is common within the first 24 h of injury and inconsistently detected by bedside monitoring.

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The entry routes and translocation mechanisms of microorganisms or particulate materials into the central nervous system remain obscure We report here that Streptococcus pneumoniae (pneumococcus), or polystyrene microspheres of similar size, appear in the meninges of the dorsal cortex of mice within minutes of inhaled delivery. Recovery of viable bacteria from dissected tissue and fluorescence microscopy show that up to at least 72 h, pneumococci and microspheres were predominantly found in the outer of the two meninges: the pachymeninx. No pneumococci were found in blood or cerebrospinal fluid.

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Down's syndrome results from trisomy of chromosome 21, a genetic change which also confers a probable 100% risk for the development of Alzheimer's disease neuropathology (amyloid plaque and neurofibrillary tangle formation) in later life. We aimed to assess the effectiveness of diffusion-weighted imaging and connectomic modelling for predicting brain amyloid plaque burden, baseline cognition and longitudinal cognitive change using support vector regression. Ninety-five participants with Down's syndrome successfully completed a full Pittsburgh Compound B (PiB) PET-MR protocol and memory assessment at two timepoints.

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: The Down syndrome population has a high prevalence for dementia, often showing their first clinical symptoms in their 40s. : In a longitudinal cohort, we investigate whether amyloid deposition at time point 1 (TP1) could predict cortical thickness change at time point 2 (TP2). The association between tau burden and cortical thickness was also examined at time point 3 (TP3).

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Article Synopsis
  • SARS-CoV-2 has been linked to various neurological and psychiatric conditions, but detailed clinical data on recovery factors is limited, hindering effective treatment strategies.
  • In a UK study of hospitalized COVID-19 patients, a multi-disciplinary team collected comprehensive information about demographics, risk factors, and neurological outcomes from 267 cases.
  • The findings revealed that cerebrovascular events were the most common issues reported, especially in younger patients, with an increased prevalence of conventional risk factors and poorer clinical outcomes compared to pre-pandemic data.
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Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited.

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Introduction: Patients aged 60 or over account for over half of the severely injured trauma patients and a traumatic brain injury is the most common injury sustained. Many of these patients are taking antiplatelet medications but there is clinical equipoise about the role of platelet transfusion in patients with traumatic intracranial haemorrhage (ICH) taking prior antiplatelet medications.

Method: A prepiloted survey was designed to explore a range of clinical issues in managing patients taking antiplatelet medications admitted with a traumatic brain injury.

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Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma.

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Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer's disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion.

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Background: Synaptic loss is a prominent and early feature of many neurodegenerative diseases.

Objectives: We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson's syndrome) and amyloid-negative corticobasal syndrome (CBS).

Methods: Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [ C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment.

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Article Synopsis
  • This study aimed to investigate the range of neurological complications associated with COVID-19 in the UK, as existing research was limited and mostly based on small samples.
  • An online network of UK neuroscience organizations was created to report and classify various neurological symptoms linked to COVID-19, such as cerebrovascular events and altered mental status, allowing for both prospective and retrospective case reporting.
  • The data collected will help to better understand how COVID-19 affects brain health, enabling more informed decisions on potential therapies and treatment strategies.
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The clinical syndromes of frontotemporal dementia are clinically and neuropathologically heterogeneous, but processes such as neuroinflammation may be common across the disease spectrum. We investigated how neuroinflammation relates to the localization of tau and TDP-43 pathology, and to the heterogeneity of clinical disease. We used PET in vivo with (i) 11C-PK-11195, a marker of activated microglia and a proxy index of neuroinflammation; and (ii) 18F-AV-1451, a radioligand with increased binding to pathologically affected regions in tauopathies and TDP-43-related disease, and which is used as a surrogate marker of non-amyloid-β protein aggregation.

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