Search

Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respond to standard antipsychotics could be fast-tracked to clozapine. Using proton magnetic resonance spectroscopy (1H-MRS), we examined the ability of glutamate and Glx (glutamate plus glutamine) in the anterior cingulate cortex (ACC) and caudate to predict response to antipsychotic treatment. A total of 89 minimally medicated patients with FEP not meeting symptomatic criteria for remission were recruited across two study sites. 1H-MRS and clinical data were acquired at baseline, 2 and 6 weeks. Response was defined as >20% reduction in Positive and Negative Syndrome Scale (PANSS) Total score from baseline to 6 weeks. In the ACC, baseline glutamate and Glx were higher in Non-Responders and significantly predicted response (P n = 42). Overall accuracy was greatest for ACC Glx (69%) and increased to 75% when symptom severity at baseline was included in the model. Glutamate metabolites in the caudate were not associated with response, and there was no significant change in glutamate metabolites over time in either region. These results add to the evidence linking elevations in ACC glutamate metabolites to a poor antipsychotic response. They indicate that glutamate may have utility in predicting response during early treatment of first episode psychosis. Improvements in accuracy may be made by combining glutamate measures with other response biomarkers.

Introduction: More than 1 in 10 people are thought to experience a mental health problem during adolescence, with most adult psychopathology beginning during this time. Experiences of stress or adversity during childhood are important risk factors for poorer mental health outcomes and are also associated with alterations in neurodevelopment. There is evidence to suggest that this relationship is mediated by inflammation and the immune system. The eBRAIN study (The Impact of Early Adversity on Trajectories of Brain Maturation and Mental Health in Young Adolescents) will assess how early life adversity might affect trajectories of brain development throughout adolescence, whether these neurobiological changes are associated with psychopathology, and if they can potentially be explained by an activation of the immune system.Methods: A cohort of 220 adolescents between the ages of 11-14 will be recruited into this study. Each participant will complete three study visits, each one year apart, at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, London (UK). At each study visit, they will be assessed with structural and functional MRI scans, biological sample collection as well as questionnaires and interviews to collect demographic information, assess experiences of adversity, and details of psychopathology. The study will also collect information about factors such as diet and nutrition, physical exercise, and cognition.Ethics and dissemination: Ethical approval for this study has been received by King's College London Research Ethics Committee (REC reference: HR-18/19-9033). Findings from the study will be published in peer-reviewed journals and disseminated at national and international conferences. Patient and public involvement (PPI) is an important component of the study, 'Study Champions' recruited from participants, their parents and teachers at collaborating schools have been invited to take an active role in study governance and dissemination.

COVID-19 was initially described as a pulmonary disease. Increasing attention is now directed to extrapulmonary disease manifestations mediated by viral tropism to the vascular endothelium. Here, we report a case of an adult patient with COVID-19 who presented to the emergency department with neurological signs disproportionate to pulmonary symptoms and was found to have a subacute ischemic stroke. Imaging studies suggested an active inflammatory vasculopathy. The case highlights the utility of vascular wall imaging studies when positive findings are present on emergent CT angiography. Current treatment algorithms should consider the addition of adjunct intracranial vessel wall imaging to assess for inflammatory vasculopathy when a patient with acute or recent COVID infection presents to the emergency department with stroke.

International studies indicate a growing problem of intimate partner violence within military families. Despite this, there has been little research into intimate partner violence perpetrated by Australian Defence Force personnel or veterans. A thematic analysis of secondary data was conducted to explore the organisational and social drivers that influence intimate partner violence occurrences by Australian Defence Force personnel, and how the Australian Defence Force enforces its zero-tolerance policy on domestic violence perpetration. Results revealed that the Australian Defence Force and Department of Veteran Affairs made no statements regarding intimate partner violence as a problem for military personnel, despite this study indicating that this population are at a greater risk of perpetration. The Australian Defence Force attributed intimate partner violence causation to ‘abnormal’ individuals or situations. This ignores the culture of hypermasculinity and emphasis on operational effectiveness that was enforced during Australian Defence Force training, and that emerged as a continuous theme throughout the results.

We herein report a case of Childhood Primary Central Nervous System (CNS) Angiitis. This case consisted of a 14-year-old girl who presented with right-sided weakness, aphasia, and a fever. A Magnetic Resonance Imaging of the brain showed multifocal areas of ischemia. Magnetic Resonance Angiography of the head and neck showed narrowing and irregularities of the left middle cerebral artery and right posterior cerebral artery. Cerebrospinal Fluid studies showed a lymphocytic pleocytosis and brain biopsy revealed leptomeningeal and perivascular inflammation. The epidemiology, presenting symptoms, work-up, pathophysiology, diagnostic criteria, and treatment of Childhood Primary CNS angiitis are discussed. This case serves as a reminder that when pediatric patients present with stroke-like symptoms inflammatory etiologies including Primary CNS Angiitis must be considered and treated appropriately in a time sensitive manner.

ObjectivesThis prospective cohort study tested for associations between baseline cognitive performance in individuals early within their first episode and antipsychotic treatment of psychosis. We hypothesised that poorer cognitive functioning at the initial assessment would be associated with poorer antipsychotic response following the subsequent 6 weeks.DesignProspective cohort .SettingNational Health Service users with a first-episode schizophrenia diagnosis, recently starting antipsychotic medication, recruited from two UK sites (King’s College London, UK and University of Manchester, UK). Participants attended three study visits following screening.ParticipantsEighty-nine participants were recruited, with 46 included in the main analysis. Participants required to be within the first 2 years of illness onset, had received minimal antipsychotic treatment, have the capacity to provide consent, and be able to read and write in English. Participants were excluded if they met remission criteria or showed mild to no symptoms.Primary and secondary outcome measuresAntipsychotic response was determined at 6 weeks using the Positive and Negative Syndrome Scale (PANSS), with cognitive performance assessed at each visit using the Brief Assessment of Cognition in Schizophrenia (BACS). The groups identified (responders and non-responders) from trajectory analyses, as well as from >20% PANSS criteria, were compared on baseline BACS performance.ResultsTrajectory analyses identified 84.78% of the sample as treatment responsive, and the remaining 15.22% as treatment non-responsive. Unadjusted and adjusted logistic regressions observed no significant relationship between baseline BACS on subscale and total performance (BACS t-score: OR=0.98, p=0.620, Cohen’s d=0.218) and antipsychotic response at 6 weeks.ConclusionsThis investigation identified two clear trajectories of treatment response in the first 6 weeks of antipsychotic treatment. Responder and non-responder groups did not significantly differ on performance on the BACS, suggesting that larger samples may be required or that an association between cognitive performance and antipsychotic response is not observable in the first 2 years of illness onset.Trial registration numberREC: 17/NI/0209.

Acute coronary syndrome is a rare complication of vasculitis. We present a case of fulminant medium-vessel vasculitis, most likely PAN, complicated by STEMI and stroke, that was successfully treated with percutaneous revascularization, high-quality stroke care, and immunosuppression. This case highlights the importance of prompt diagnosis and treatment of vasculitis and the recognition of coronary and cerebral ischemia as potentially serious complications.

Introduction: The National Institutes of Health Stroke Scale (NIHSS) is widely used for rapid assessment of neurologic deficits in acute stroke. Multiple components of the scale require intact language function, which may be difficult for English-speaking providers to assess in non-English speaking patients (NESP). We sought to characterize patterns of NIHSS scoring in English-speaking patients (ESP) and NESP. Methods: This was a retrospective study of consecutive stroke alert cases who presented to the emergency department at our primarily English-speaking comprehensive stroke center. Baseline characteristics and clinical data including NIHSS components were compared between ESP and NESP. Chi-squared/Fisher’s exact statistics were used to compare frequencies and T-tests were used to compare means. Relative risks were calculated for language effects on NIHSS components, controlling for gender, age, race, and stroke diagnosis. Results: A total of 1166 patients were included, of which 87.5% were ESP and 12.5% were NESP. There were no significant differences between groups in total NIHSS scores or in frequencies of stroke diagnosis, tissue plasminogen activator treatment, or endovascular treatment. For individual NIHSS components, NESP were more likely than ESP to score for level of consciousness questions (34.9% vs 22.3%, adjusted RR 1.91, CL 1.39-2.62, p=0.0005), level of consciousness commands (21.9% vs 10.1%, adjusted RR 3.62, CL 2.42-5.43, p Conclusions: Despite similarities in total NIHSS scoring between NESP and ESP, scoring of individual components heavily dependent on language function and comprehension differed between groups. NESP were more likely to be assessed as aphasic, unable to answer questions, and unable to follow commands. Disparities in NIHSS scoring trends raise questions for further investigation into possible underlying pathophysiologic mechanisms, potential provider biases from language barriers that may influence clinical assessment, and the role of more inclusive screening tools and interventions to help mitigate these gaps.

Objective To determine the feasibility of using a machine learning algorithm to screen for large vessel occlusions (LVO) in the Emergency Department (ED). Materials and methods A retrospective cohort of consecutive ED stroke alerts at a large comprehensive stroke center was analyzed. The primary outcome was diagnosis of LVO at discharge. Components of the National Institutes of Health Stroke Scale (NIHSS) were used in various clinical methods and machine learning algorithms to predict LVO, and the results were compared with the baseline method (aggregate NIHSS score with threshold of 6). The Area-Under-Curve (AUC) was used to measure the overall performance of the models. Bootstrapping (n = 1000) was applied for the statistical analysis. Results Of 1133 total patients, 67 were diagnosed with LVO. A Gaussian Process (GP) algorithm significantly outperformed other methods including the baseline methods. AUC score for the GP algorithm was 0.874 ± 0.025, compared with the simple aggregate NIHSS score, which had an AUC score of 0.819 ± 0.024. A dual-stage GP algorithm is proposed, which offers flexible threshold settings for different patient populations, and achieved an overall sensitivity of 0.903 and specificity of 0.626, in which sensitivity of 0.99 was achieved for high-risk patients (defined as initial NIHSS score > 6). Conclusion Machine learning using a Gaussian Process algorithm outperformed a clinical cutoff using the aggregate NIHSS score for LVO diagnosis. Future studies would be beneficial in exploring prospective interventions developed using machine learning in screening for LVOs in the emergent setting.

Every 40 seconds, a stroke occurs in the United States. Strokes both disable patients and cause substantial cost to society, remaining among the top causes of long-term disability and costing an estimated $45.5 billion annually, of which $17.5 billion are due to indirect costs from lost productivity and mortality.1 Large vessel occlusions account for the majority of acute ischemic strokes that result in moderate to severe disability or death.2 For eligible patients with large vessel occlusions, endovascular treatment with mechanical thrombectomy, established as standard of care, has proven safe and efficacious up to 16–24 hours out from last known well.3,4 Within the 6-hour window, multiple studies have found better functional outcomes and lower degrees of disability with earlier intervention.5,6

Background Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. Methods We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2–4 consecutive days no later than 7 days from baseline. It will continue 4–5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2–3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. Discussion The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies. Trial registration ISRCTN, 11177045. Registered on 2 May 2017. EudraCT, 2016-000118-31. Registered on 22 November 2016. ClinicalTrials.gov, NCT03194815. Registered on 21 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3336-1) contains supplementary material, which is available to authorized users.

Antibodies against N-methyl D-aspartate receptor (NMDAR) and other neuronal cell surface targets are recognised associations of immunotherapy-responsive autoimmune encephalitis. Initially, patients present with symptoms of behavioural change and psychosis, often subsequently developing seizures and cognitive impairment, rapidly progressing over a few weeks to develop a life-threatening combination of autonomic instability and loss of consciousness.1 There is in vitro and in vivo evidence that these antibodies are pathogenic and directly cause encephalitis. Although never formally demonstrated in a controlled trial, open label clinical studies show that patients receiving immunotherapy, such as intravenous immunoglobulins (IVIG) or plasma exchange (PLEX) with or without corticosteroids, have better recovery and reduced relapse rates. Therefore, clinical consensus guidelines recommend that immunotherapy should be given as soon as possible after diagnosis.2 Several studies have assessed the prevalence of these antibodies in purely psychiatric presentations. NMDAR antibodies are the most commonly identified; in some studies, these are twice as prevalent in patients with early psychosis than in healthy controls, being seen at rates of between 4% and 12% of cases (OR 2.70, 95% CI 1.11 to 6.56).3 We have seen a number of such cases which respond to immunotherapy in an uncontrolled study.4 We have therefore proposed a randomised, placebo-controlled trial of immunotherapy in psychosis associated with antineuronal antibodies, to inform clinical practice and to advance understanding of the …

Epistemological beliefs, learners' general understandings about the nature of knowledge and learning, have emerged as a factor influencing self-regulated learning (Jehng, Johnson, & Anderson, 1993). The epistemological beliefs of underprepared undergraduates were assessed at the beginning and end of the students' first five-week session. Results demonstrated that the epistemological beliefs of underprepared undergraduates tended to be naive and to change during initial college experience. Investigations of the underlying structure of these beliefs did not demonstrate the five distinct dimensions demonstrated by previous research but rather as two general dimensions: 1) the nature of learning and 2) the nature of knowledge.

BACKGROUND: In minimally invasive surgery, there is increased reliance on real-time 2-dimensional images. The fibre-optic light lead is one of the most frequently damaged elements of the 'imaging chain', leading to a poor quality picture. METHODS: Light leads with a honeycomb projection were connected to a light source and the resulting beam directed at a sheet of paper. Darkened sectors with diminished or absent light transmission were recorded. RESULTS: All suitable light leads in routine use were examined. A mean of 22.2% (SD 7.8%) of the projection had diminished or absent light transmission. CONCLUSION: Sub-optimal endoscopic equipment was in routine use.

Background: With newly-extended treatment windows for endovascular therapy in emergent large vessel occlusions, it is increasingly important to identify thrombectomy-eligible patients without overwhelming resources dedicated to acute stroke care. We devised a simple paradigm to classify patient's presenting neurologic symptoms to screen for large vessel occlusions. Methods: We reviewed the presenting symptoms, imaging findings, and final diagnoses of consecutive emergency department stroke alert cases. Patients were classified based on their neurologic exams as focal objective, focal subjective, or nonfocal. Outcomes of final diagnoses of acute ischemic stroke and large vessel occlusions were compared across groups. Comparisons were made to other large vessel occlusion prediction scales. Results: Of 521 patients, 342 (65.6%) were categorized as focal objective, 142 (27.2%) as focal subjective, and 37 (7.1%) as nonfocal. Ischemic stroke and large vessel occlusions were diagnosed in 114 (21.9%) and 27 (5.2%) of patients, respectively. Classification as focal objective significantly predicted stroke (odds ratio 3.77; 95% confidence interval 2.17-6.55) and captured all large vessel occlusions (P = .0001). The focal objective categorization was the only tool which achieved 100% sensitivity for large vessel occlusions (with a specificity of 36%) compared to other large vessel occlusion prediction tools. Conclusions: Patients who presented as stroke alerts without focal neurologic symptoms were unlikely to have large vessel occlusions. With high sensitivity, classifying patients' neurologic exams into focal objective versus subjective or nonfocal categories may serve as a useful tool to screen for large vessel occlusions and prevent unnecessary emergent workup in patients unlikely to be endovascular candidates.