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Functional neurological disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with FND, suggesting that gaps remain in our systems-level neurobiological understanding. As such, other important physiological variables, including autonomic, endocrine, and inflammation findings, need to be contextualized for a more complete mechanistic picture.The investigators conducted a systematic review and meta-analysis of available case-control and cohort studies of FND. PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1900, to September 1, 2020, that investigated autonomic, endocrine, and inflammation markers in patients with FND. Sixty-six of 2,056 screened records were included in the review, representing 1,699 patients; data from 20 articles were used in the meta-analysis.Findings revealed that children and adolescents with FND, compared with healthy control subjects (HCs), have increased resting heart rate (HR); there is also a tendency toward reduced resting HR variability in patients with FND across the lifespan compared with HCs. In adults, peri-ictal HR differentiated patients with functional seizures from those with epileptic seizures. Other autonomic and endocrine profiles for patients with FND were heterogeneous, with several studies highlighting the importance of individual differences.Inflammation research in FND remains in its early stages. Moving forward, there is a need for the use of larger sample sizes to consider the complex interplay between functional neurological symptoms and behavioral, psychological, autonomic, endocrine, inflammation, neuroimaging, and epigenetic/genetic data. More research is also needed to determine whether FND is mechanistically (and etiologically) similar or distinct across phenotypes.

Background and purpose Functional neurological disorder (FND) is common, and symptoms can be severe. There have been no international large-scale studies of patient experiences of FND. Methods A patient questionnaire was created to assess FND patient characteristics, symptom comorbidities and illness perceptions. Respondents were recruited internationally through an open access questionnaire via social media and patient groups over a month-long period. Results In total, 1048 respondents from 16 countries participated. Mean age was 42 years (86% female). Median FND symptom duration was 5 years, and median time from first symptom to diagnosis was 2 years. Mean number of current symptoms (core FND and associated) was 9.9. Many respondents had associated symptoms, for example fatigue (93%), memory difficulties (80%) and headache (70%). Self-reported psychiatric comorbidities were relatively common (depression, 43%; anxiety, 51%; panic, 20%; and post-traumatic stress disorder, 22%). Most respondents reported that FND had multiple causes, including physical and psychological. Conclusions This large survey adds further evidence that people with FND typically have high levels of multiple symptom comorbidity with resultant distress. It also supports the notion that associated physical symptoms are of particular clinical significance in FND patients. Dualistic ideas of FND were not supported by respondents, who generally preferred to conceptualize the disorder as one at the interface of mind and brain. The need for a broad approach to this poorly served patient group is highlighted. Potential selection and response biases due to distribution of the survey online, mostly via FND patient groups, are a key limitation.

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network-trauma relationships in this population. In this neuroimaging-gene expression study, we used two graph theory approaches to elucidate ELM subtype effects on resting-state functional connectivity architecture in 30 patients with motor FND. Twenty-one individuals with comparable depression, anxiety, and ELM scores were used as psychiatric controls. Thereafter, we compared trauma endophenotypes in FND with regional differences in transcriptional gene expression as measured by the Allen Human Brain Atlas (AHBA). In FND patients only, we found that early-life physical abuse severity, and to a lesser extent physical neglect, correlated with corticolimbic weighted-degree functional connectivity. Connectivity profiles influenced by physical abuse occurred in limbic (amygdalar-hippocampal), paralimbic (cingulo-insular and ventromedial prefrontal), and cognitive control (ventrolateral prefrontal) areas, as well as in sensorimotor and visual cortices. These findings held adjusting for individual differences in depression/anxiety, PTSD, and motor phenotypes. In FND, physical abuse also correlated with amygdala and insula coupling to motor cortices. In exploratory analyses, physical abuse correlated connectivity maps overlapped with the AHBA spatial expression of three gene clusters: (i) neuronal morphogenesis and synaptic transmission genes in limbic/paralimbic areas; (ii) locomotory behavior and neuronal generation genes in left-lateralized structures; and (iii) nervous system development and cell motility genes in right-lateralized structures. These circuit-specific architectural profiles related to individual differences in childhood physical abuse burden advance our understanding of the pathophysiology of FND.

BackgroundCatatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia.MethodsElectronic healthcare records were searched for validated clinical diagnoses of catatonia. In a case–control study, demographics and inflammatory markers were compared in psychiatric inpatients with and without catatonia. In a cohort study, the two groups were compared in terms of their duration of admission and mortality.ResultsWe identified 1456 patients with catatonia (of whom 25.1% had two or more episodes) and 24 956 psychiatric inpatients without catatonia. Incidence was 10.6 episodes of catatonia per 100 000 person-years. Patients with and without catatonia were similar in sex, younger and more likely to be of Black ethnicity. Serum iron was reduced in patients with catatonia [11.6 v. 14.2 μmol/L, odds ratio (OR) 0.65 (95% confidence interval (CI) 0.45–0.95), p = 0.03] and creatine kinase was raised [2545 v. 459 IU/L, OR 1.53 (95% CI 1.29–1.81), p < 0.001], but there was no difference in C-reactive protein or white cell count. N-Methyl-d-aspartate receptor antibodies were significantly associated with catatonia, but there were small numbers of positive results. Duration of hospitalisation was greater in the catatonia group (median: 43 v. 25 days), but there was no difference in mortality after adjustment.ConclusionsIn the largest clinical study of catatonia, we found catatonia occurred in approximately 1 per 10 000 person-years. Evidence for a proinflammatory state was mixed. Catatonia was associated with prolonged inpatient admission but not with increased mortality.

Adverse life events precede the onset of functional neurological disorder (FND, also known as conversion disorder) more commonly than other neuropsychiatric conditions, but their aetiological role is unclear. We conducted a systematic review and quantitative analysis of the type, timing and number of life events preceding the onset of FND in adults, and a meta-analysis of the proportions of types of events in controlled studies. Fifty-one studies of different designs, covering 4247 patients, were eligible for inclusion. There was no clear majority of any type of preceding event. Family problems were the most common category of events, followed by relationship problems. Females were more likely to experience preceding family/relationship problems than males, who reported more work problems. Family problems were the commonest type of preceding event in studies in developing countries, whereas family and health problems were equally common in developed countries. Abuse was associated with early symptom onset, while patients with later onset were more likely to report family problems. The median number of events was one, and the events occurred closer to onset than in controls. Meta-analysis found that family, relationship and work events were all relatively more common in patients than pathological controls, as were events where symptoms might provide a solution to the stressor. In conclusion, although a range of events precede the onset of FND, they do not appear to do so uniformly. This may support a different aetiological role for stressors than in other disorders, although the support is indirect and the quality generally low.

The scientific community rapidly responded to the COVID-19 pandemic by developing novel SARS-CoV-2 vaccines (table 1). As of early June 2021, an estimated 2 billion doses have been administered worldwide.1 Neurological adverse events following immunisation (AEFI), such as cerebral venous sinus thrombosis and demyelinating episodes, have been reported. In some countries, these have led to the temporary halting of both vaccine trials and roll-out programmes. In the absence of clear evidence of causal associations between the vaccine and adverse events, or the rarity of the AEFIs themselves, programmes have thus far been restarted, although sometimes with modifications to recommendations.2 View this table: Table 1 SARS-CoV-2 vaccines approved for use by at least one regulatory body at the time of submission (early June 2021)71 Transient influenza-like symptoms such as headache, myalgia and fatigue have been reported in up to 5% of SARS-CoV-2 vaccine recipients in clinical trials,3 4 although these symptoms often indicate an appropriate immune response to vaccination.5 More severe potential adverse effects in the open-label phase of vaccine roll-outs are being collected through national surveillance systems. In the USA, roughly 372 adverse events have been reported per million doses, which is a lower rate than expected based on the clinical trials.6 In the UK, adverse events are reported via the Coronavirus Yellow Card reporting website. As of early June 2021, approximately 250 000 Yellow Cards have been submitted, equating to around three to seven Yellow Cards per 1000 doses.7 For comparison, the 2010 Pandemrix vaccination had a rate of around 0.6 Yellow Card submissions per 1000 doses.8 Increased pharmacovigilance surrounding SARS-CoV-2 vaccinations may lead to surveillance bias,9 safety alerts may lead to notoriety bias10 and recall bias may also occur. Nevertheless, with large numbers of people being vaccinated, often with a two-dose schedule, rare complications …

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients 60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials., Ross Russell et al. report novel details of COVID-19 neurological complications: multiple overlapping diagnoses in the same patients, a severe encephalopathy atypical for delirium, and a lowered threshold for stroke in younger adults. Higher age, pre-morbid frailty score and white cell count predicted clinical outcome., Graphical Abstract Graphical Abstract

Historical epidemiological perspectives from past pandemics and recent neurobiological evidence link infections and psychoses, leading to concerns that COVID-19 will present a significant risk for the development of psychosis. But are these concerns justified, or mere sensationalism? In this article we review the historical associations between viral infection and the immune system more broadly in the development of psychosis, before critically evaluating the current evidence pertaining to SARS-CoV-2 and risk of psychosis as an acute or post-infectious manifestation of COVID-19. We review the 42 cases of psychosis reported in infected patients to date, and discuss the potential implications of in utero infection on subsequent neurodevelopment and psychiatric risk. Finally, in the context of the wider neurological and psychiatric manifestations of COVID-19 and our current understanding of the aetiology of psychotic disorders, we evaluate possible neurobiological and psychosocial mechanisms as well as the numerous challenges in ascribing a causal pathogenic role to the infection.

Highlights • 1st Neuroimaging Workgroup Meeting in Functional Neurological Disorder (FND). • Underscores the importance of FND cohort characterization in brain imaging research. • Details methodological approaches taken in FND neuroimaging research to date. • Research agenda proposed to definitely elucidate the neural circuitry of FND. • Discussions underway regarding having FND researchers join the ENIGMA consortium., Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart – leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using “rule-in” examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Worldwide SARS-CoV-2 vaccination campaigns for prevention of COVID-19 are currently underway. In clinical trials and in open-label monitoring the vaccines have shown efficacy against COVID-19 and there have been limited and transient side effects. Previous vaccination campaigns have taught us that neurological adverse events to vaccinations can occur. In this review, we summarise what is already known about neurological and neuropsychiatric adverse events of COVID-19 vaccinations, and place this in the context of historical vaccination campaigns. There have been a number of neurological and neuropsychiatric adverse events following immunisation (AEFI) in association with SARS-CoV-2 vaccinations, however in each case there is either no definitive evidence currently to support causality or recognised adverse events are extremely rare. Causality assessment aids such as the Causality Assessment of an Adverse Event Following Immunization from the World Health Organisation and the Bradford Hill criteria may help us better understand potential neurological and neuropsychiatric adverse events to COVID-19 vaccinations. Functional neurological disorder (FND) can be precipitated by the process of vaccination and has previously been noted to potentially spread between individuals, particularly in younger communities. Importantly FND does not implicate the vaccine constituents and therefore should not hamper ongoing vaccination campaigns. Although neurological and neuropsychiatric AEFI may occur after SARS-CoV-2 vaccinations, at present there are no common causally associated neurological adverse events. It is likely that some patients will develop FND in response to vaccination, although this does not implicate vaccine constituents. In cases of future serious neurological or neuropsychiatric AEFIs, judicious and rapid assessment of causality must occur. In general, the benefits of ARS-CoV-2 vaccination at present outweigh the risks from a neurological standpoint, although in specific situations the risk-benefit ratio will vary depending on geographic and demographic factors as well as population risk factors. Ensuring as minimal disruption as possible to ongoing swift worldwide vaccination campaigns is essential to establish the herd immunity required to end the COVID-19 pandemic.

Encephalopathy is a common complication of COVID-19 that can both be a challenge to manage and also negatively impacts prognosis. Whilst encephalopathy may be due to common systemic causes, such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma, cerebrovascular involvement and seizures, which may be disproportionate to COVID-19 severity and which require specific management. The aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through a consensus agreement of the Global COVID-19 Neuro-Research Coalition. A systematic literature search of Medline, MedRxiv, and BioRx was conducted between 1st January 2020 and 11th June 2021 with additional review of references cited within the identified bibliographies. A modified Delphi-approach was then undertaken to develop recommendations along with a parallel approach to score the strength of both the recommendation and the supporting evidence. This manuscript presents analysis of contemporaneous evidence for definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and acute and long-term management.

Background:Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.Methods:During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.Findings:The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. Interpretation:To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Funding: None.

An increasing proportion of cognitive difficulties are recognized to have a functional cause, the chief clinical indicator of which is internal inconsistency. When these symptoms are impairing or distressing, and not better explained by other disorders, this can be conceptualized as a cognitive variant of functional neurological disorder, termed functional cognitive disorder (FCD). FCD is likely very common in clinical practice but may be under-diagnosed. Clinicians in many settings make liberal use of the descriptive term mild cognitive impairment (MCI) for those with cognitive difficulties not impairing enough to qualify as dementia. However, MCI is an aetiology-neutral description, which therefore includes patients with a wide range of underlying causes. Consequently, a proportion of MCI cases are due to non-neurodegenerative processes, including FCD. Indeed, significant numbers of patients diagnosed with MCI do not ‘convert’ to dementia. The lack of diagnostic specificity for MCI ‘non-progressors’ is a weakness inherent in framing MCI primarily within a deterministic neurodegenerative pathway. It is recognized that depression, anxiety and behavioural changes can represent a prodrome to neurodegeneration; empirical data are required to explore whether the same might hold for subsets of individuals with FCD. Clinicians and researchers can improve study efficacy and patient outcomes by viewing MCI as a descriptive term with a wide differential diagnosis, including potentially reversible components such as FCD. We present a preliminary definition of functional neurological disorder–cognitive subtype, explain its position in relation to other cognitive diagnoses and emerging biomarkers, highlight clinical features that can lead to positive diagnosis (as opposed to a diagnosis of exclusion), and red flags that should prompt consideration of alternative diagnoses. In the research setting, positive identifiers of FCD will enhance our recognition of individuals who are not in a neurodegenerative prodrome, while greater use of this diagnosis in clinical practice will facilitate personalized interventions.

Functional neurological (conversion) disorder (FND) is a prevalent and disabling condition at the intersection of neurology and psychiatry. Advances have been made in elucidating an emerging pathophysiology for motor FND, as well as in identifying evidenced-based physiotherapy and psychotherapy treatments. Despite these gains, important elements of the initial neuropsychiatric assessment of functional movement disorders (FND-movt) and functional limb weakness/paresis (FND-par) have yet to be established. This is an important gap from both diagnostic and treatment planning perspectives. In this article, the authors performed a narrative review to characterize clinically relevant variables across FND-movt and FND-par cohorts, including time course and symptom evolution, precipitating factors, medical and family histories, psychiatric comorbidities, psychosocial factors, physical examination signs, and adjunctive diagnostic tests. Thereafter, the authors propose a preliminary set of clinical content that should be assessed during early-phase patient encounters, in addition to identifying physical signs informing diagnosis and potential use of adjunctive tests for challenging cases. Although clinical history should not be used to make a FND diagnosis, characteristics such as acute onset, precipitating events (e.g., injury and surgery), and a waxing and waning course (including spontaneous remissions) are commonly reported. Active psychiatric symptoms (e.g., depression and anxiety) and ongoing psychosocial stressors also warrant evaluation. Positive physical examination signs (e.g., Hoover's sign and tremor entrainment) are key findings, as one of the DSM-5 diagnostic criteria. The neuropsychiatric assessment proposed emphasizes diagnosing FND by using "rule-in" physical signs while also considering psychiatric and psychosocial factors to aid in the development of a patient-centered treatment plan.

Background and purpose: Cauda equina syndrome (CES) is a neurosurgical emergency which warrants lumbar magnetic resonance imaging (MRI). Many patients with suggestive symptoms of CES have no radiological correlate. A functional (non-organic) aetiology has been proposed in some, but currently little is known about this patient group and their clinical outcomes. Methods: At a tertiary referral centre, 155 adult patients underwent urgent lumbar MRI for suspected CES in 1 year from December 2014. Data regarding clinical symptoms and follow-up were obtained from records. Patients were divided into CES (n = 25), radiculopathy (n = 68) and scan-negative (SN) groups (n = 62) from scans. Up to 3 years post-discharge, postal questionnaires were sent to patients with Oswestry Disability Index, Pain Catastrophizing score, Patient Health Questionnaire (PHQ) 9, Generalized Anxiety Disorder (GAD) 7, PHQ 15 and Work and Social Adjustment Scale measures. Results: No clinical symptoms were found to differentiate CES from SN patients. Functional comorbidities were significantly more common in SN patients but mental health diagnosis frequency did not differ. Follow-up was variable with no consistent referral pathways, particularly for the SN group. 33% (n = 47) responded to the postal questionnaires; high levels of pain, symptom chronicity and disability were ubiquitous but self-reported mental health diagnoses and PHQ 15 were higher for SN patients. Conclusions: Conflicting data suggest further research is needed to investigate the prevalence of mental illness and somatic symptoms in SN cases. SN patients have higher rates of comorbid functional disorders and inconsistent referral pathways. Self-report measures indicate impaired quality of life across all groups. The low response rate limits the generalizability of findings but neuropsychiatric assessment and care pathway optimization should be considered.

OBJECTIVE Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally. METHODS We compared the cognitive task performance of FND, CFS, and healthy control (HC) groups. The tasks assessed attentional bias toward illness-relevant stimuli (visual probe task), attentional control (attention network task), and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue, and general health. RESULTS Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS, and 51 HC participants were included. Although participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13, p = .002, d = 0.624), individuals with FND did not (t = -1.59, p = .118, d = 0.379). Both the FND (t = 3.08, p = .003, d = 0.759) and CFS (t = 2.74, p = .007, d = 0.548) groups displayed worse attentional control than did the HC group. Similarly, the FND (t = 3.63, p < .001, d = 0.801) and CFS groups (t = 4.58, p < .001, d = 0.909) showed more somatic interpretative bias than did the HC group. CONCLUSIONS Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias toward somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.

Objectives: This International League Against Epilepsy (ILAE) Report: (a) summarizes the literature about “driving and psychogenic nonepileptic seizures (PNES)”; (b) presents the views of international experts; and (c) proposes an approach to assessing the ability of persons with PNES (PwPNES) to drive. Methods: Phase 1: Systematic literature review. Phase 2: Collection of international expert opinion using SurveyMonkey®. Experts included the members of the ILAE PNES Task Force and individuals with relevant publications since 2000. Phase 3: Joint analysis of the findings and refinement of conclusions by all participants using email. As an ILAE Report, the resulting text was reviewed by the Psychiatry Commission, the ILAE Task Force on Driving Guidelines, and Executive Committee. Results: Eight studies identified by the systematic review process failed to provide a firm evidence base for PNES-related driving regulations, but suggest that most health professionals think restrictions are appropriate. Twenty-six experts responded to the survey. Most held the view that decisions about driving privileges should consider individual patient and PNES characteristics and take account of whether permits are sought for private or commercial driving. Most felt that those with active PNES should not be allowed to drive unless certain criteria were met and that PNES should be thought of as “active” if the last psychogenic seizure had occurred within 6 months. Significance: Recommendations on whether PwPNES can drive should be made at the individual patient level. Until future research has determined the risk of accidents in PwPNES a proposed algorithm may guide decisions about driving advice. Fil: Asadi Pooya, Ali A.. Shiraz University Of Medical Sciences; Irán Fil: Nicholson, Timothy R.. King's College London; Reino Unido Fil: Pick, Susannah. King's College London; Reino Unido Fil: Baslet, Gaston. Harvard Medical School; Estados Unidos Fil: Benbadis, Selim R.. University Of South Florida; Estados Unidos Fil: Beghi, Massimiliano. Department of Mental Health; Italia Fil: Brigo, Francesco. Franz Tappeiner Hospital; Italia Fil: Buchhalter, Jeffrey. University of Calgary; Canadá Fil: D`alessio, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Dworetzky, Barbara. Harvard Medical School; Estados Unidos Fil: Gigineishvili, David. Tbilisi State University; Estados Unidos Fil: Kanaan, Richard A.. University of Melbourne; Australia Fil: Kozlowska, Kasia. University of Sydney; Australia Fil: LaFrance, W. Curt. University Brown; Estados Unidos Fil: Lehn, Alexander. Princess Alexandra Hospital; Australia Fil: Perez, David L.. Harvard Medical School; Estados Unidos Fil: Popkirov, Stoyan. No especifíca; Fil: Pretorius, Chrisma. No especifíca; Fil: Szaflarski, Jerzy P.. No especifíca; Fil: Tolchin, Benjamin. University of Yale; Estados Unidos Fil: Valente, Kette. Universidade de Sao Paulo; Brasil Fil: Stone, Jon. University of Edinburgh; Reino Unido Fil: Reuber, Markus. The University Of Sheffield; Reino Unido

Funder: UCLH Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100012317, Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272, INTRODUCTION: Neuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias. METHODS: We searched Medline and Embase for studies reporting associations between neuronal surface antibodies in all-cause dementia versus controls. Random-effects meta-analysis was used to pool adjusted estimates across studies. RESULTS: Six studies were included, all reporting frequency of serum NMDAR antibodies in dementia with four also reporting frequency in atypical dementias. Both IgG [OR = 8.09 (1.51; 56.85), p = 0.036] and IgA/IgM NMDAR antibodies [OR = 42.48 (11.39; 158.52), p < 0.001] were associated with atypical dementia, but neither were associated with all-cause dementia. DISCUSSION: In the first meta-analysis to explore this literature, serum IgG and IgA/IgM NMDAR antibodies were significantly more common in atypical dementias. However, methodological issues and small-sample sizes necessitate caution interpreting this result. Further studies measuring both serum and CSF antibodies are needed to investigate the role of neuronal antibodies in dementia, since evidence of pathogenicity in even a subset of patients could pave the way for novel treatment options.

ObjectivesWe aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes.MethodsA systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group.ResultsFive FND-specific measures were identified—three clinician-rated and two patient-rated—but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost–utility (eg, healthcare resource use and quality-adjusted life years).ConclusionsThere are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

Introduction: We aimed to examine susceptibility to dissociation and the impact of dissociation on interoceptive processing in individuals with functional neurological disorder (FND). We hypothesised that dissociative states would be elevated and interoceptive accuracy and awareness impaired at baseline in people with FND, and that such differences would be exacerbated following acute dissociation. Methods: Nineteen adults with FND were compared to 20 healthy controls. A modified heart-beat tracking task measured interoceptive accuracy and awareness (confidence) before and after a validated dissociation induction procedure. An exteroceptive processing control task was included. Mann–Whitney tests and r-values (effect size) were computed for between-group comparisons. Results: The FND group displayed elevated dissociation at baseline (p = 0.001, r = 0.528) compared to controls which increased following dissociation-induction (p r = 0.663). Interoceptive accuracy did not differ between groups at baseline (p = 0.967, r = 0.009); however, the FND group had lower accuracy scores post-induction (p = 0.021, r = 0.379). A negative correlation (trend) between change scores for dissociation and interoceptive accuracy was noted (rs = −0.411, p = 0.057). Confidence ratings on interoceptive and exteroceptive processing tasks were lower in the FND group (p-values r-values 0.331–0.489). Conclusions: Individuals with FND experienced greater susceptibility to dissociation, metacognitive deficits and impaired interoceptive accuracy than controls after acute dissociation.

H.A.B. is funded by a National Institute for Health Research (NIHR) Clinical Lectureship. R.B. is supported by a NIHR Academic Clinical Fellowship. D.J.B. is funded by Alzheimer's Research UK & Rosetrees. D.J.B., M.R. and A.V. acknowledge the support of the National Institute for Health Research Sheffield Biomedical Research Centre (Translational Neuroscience). M.J.E. is funded by NIHR and the Medical Research Council. S.M.F. is funded by the Wellcome Trust & the Royal Society. J.H. is funded by a Wellcome Clinical Research Career Development Fellowship. R.H., N.C.F., J.M.S. and M.N.R. acknowledge the support of the National Institute for Health Research University College London Hospitals Biomedical Research Centre. L.M. receives philanthropic funding from Baillie Gifford. T.R.N. is funded by an NIHR Clinician Scientist Award. C.P. is funded by the Innovative Medicines Initiative, BRACE, and the David Telling Charitable Trust. J.S. is supported by a National Research Scotland Career Researcher Fellowship. This publication presents independent research; the views expressed are those of the authors and not necessarily those of the specified funding bodies.

Antibodies to the voltage-gated potassium channel (VGKC) complex and glutamic acid decarboxylase (GAD) have been reported in some cases of psychosis. We conducted the first systematic review and meta-analysis to investigate their prevalence in people with psychosis and report a case series of VGKC-complex antibodies in refractory psychosis. Only five studies presenting prevalence rates of VGKC seropositivity in psychosis were identified, in addition to our case series, with an overall prevalence of 1.5% (25/1720) compared to 0.7% in healthy controls (12/1753). Meta-analysis established that the pooled prevalence of GAD65 autoantibodies was 5.8% (95% confidence interval [CI]: 2.0-15.6%; I2 = 91%; nine studies) in psychotic disorders, with a prevalence of 4.6% (95%CI: 1.2-15.9%; nine studies; I2 = 89%) and 6.2% (95%CI: 1.2-27.0%; two studies; I2 = 69%) in schizophrenia and bipolar disorder, respectively. People with psychosis were more likely to have GAD65 antibodies than controls (odds ratio [OR], 2.24; 95%CI: 1.28-3.92%; P = 0.005; eight studies; I2 = 0%). Among 21 participants with treatment-resistant psychosis, none had VGKC antibodies. The prevalence of VGKC antibodies is low in psychosis. Our preliminary meta-analysis suggests that GAD autoantibodies are more common in people with psychosis than in controls, although few studies accounted for the possibility of co-existing type 1 diabetes mellitus and the clinical significance of reported GAD titers remains unclear. The paucity of studies reporting thresholds for defining GAD abnormality and rates of comorbid type 1 diabetes mellitus precludes interpretations regarding the influence of GAD antibodies on the development of psychotic disorders and may have led to an overestimate of the prevalence of GAD. Our case series fails to support the hypothesis that VGKC antibodies are linked to treatment resistance in psychosis, but the literature to date is remarkably sparse.

From the simple message of ‘I will please’ (Latin placēbō ) encapsulated in a sugar pill, to the famous theatrics of Jean-Martin Charcot’s hypnotic seizure inductions and treatments (figure 1), implicit and explicit narratives of healing and illness have been noted to exert a particularly strong influence on functional neurological disorder (FND). Although the placebo effect is near universal in medicine, and cultural frameworks are relevant for any illness experience, expectancy plays a more central mechanistic role in FND.1 Techniques of suggestion are still occasionally used in neurology practice, specifically to diagnose functional motor deficits by demonstrating reversibility,2 or to provoke dissociative seizures during video electroencephalography monitoring to enable a definitive diagnosis.3 Figure 1 The painting ‘Une lecon clinique a la Salpetriere’ (1887) by Andre Brouillet depicts Jean-Martin Charcot inducing neurological symptoms through hypnotic suggestion. His student Joseph Babinski (pictured holding the patient) later proposed changing the term hysteria to pithiathism (from Ancient Greek peithō , meaning ‘I convince’ ), emphasising the suggestibility of symptoms as a cardinal feature. Source: …

For over 4 months, we have been in the privileged position of witnessing real-time trends in the literature via our weekly curation of The Neurology and Neuropsychiatry of COVID-19 blog.1 There is an emerging recognition of the need to report the severity and outcomes of neurological complications of SARS-CoV-2 infection. Stroke is a rare but well-documented complication, with most prevalence estimates varying slightly around 0.8%.2 It is therefore important to elucidate both those at risk of developing stroke and stratifying those at risk of more severe outcomes when stroke occurs. We were greatly interested to read the letter by Dmytriw et al ,3 which highlighted potential racial disparities in outcomes from ischaemic stroke after COVID-19. Their novel study built on the hypothesis that black and minority ethnic (BAME) individuals have poorer outcomes from COVID-19 in general.4 An editorial commentary by Renieri5 further highlighted the need to elucidate mechanisms that may drive an interaction between stroke and COVID-19 to explain increased mortality in ethnic minorities. Previously also, Katz et al reported that patients with stroke with COVID-19 were more likely to be from a BAME population than patients with stroke without COVID-19. The potential over-representation of BAME individuals in COVID-19 stroke cohorts …

The development and selection of optimal outcome measures is increasingly recognized as a key component of evidence-based medicine, particularly the need for the development of a standardized set of measures for use in clinical trials. This process is particularly complex for functional neurological disorder (FND) for several reasons. FND can present with a wide range of symptoms that resemble the full spectrum of other neurological disorders. Additional physical (e.g., pain, fatigue) and psychological (e.g., depression, anxiety) symptoms are commonly associated with FND, which also can be highly disabling with implications for prognosis, and warrant concurrent assessment, despite an unclear etiological relationship with FND. Furthermore, several unique clinical aspects of FND make it likely that the usual prioritization of "objective" (or clinician-rated) over "subjective" (or patient-rated) measures might not be appropriate. Self-report measures may be more clinically meaningful in this patient population. Despite being a common and disabling disorder, there has been little research into outcome measures in FND, and to date trials have largely used measures designed for the assessment of other disorders. An international FND Core Outcome Measure group (FND-COM) has been established to develop a consensus battery of outcomes for FND: a "core outcome set." In this perspective article, the authors reviewed the process of outcome measure development and selection before considering the specific features of FND affecting the development of a core outcome set, as well as a research agenda to optimize outcome measurement in this complex neuropsychiatric disorder.

Purpose The aim of this multicenter international cross-cultural study was to compare clinical variables in a large sample of people with adult-onset psychogenic nonepileptic seizures (PNES). Methods In this retrospective study, we evaluated persons with documented PNES, who were older than 16 years of age at the onset, from four countries (i.e., Iran, Brazil, Venezuela, and Argentina) regarding their age, gender, PNES semiology, and possible predisposing factors. Results We included 389 patients (244 from Iran, 66 from Brazil, 51 from Venezuela, and 28 from Argentina). Age at diagnosis was 32 ± 9 years (range: 17–64 years), and age at the onset of seizures was 27 ± 8 years (range: 17–49 years). There was a female predominance in all countries. The demographic characteristics and factors associated with PNES were similar among the countries. However, there were significant semiological differences among the countries. Conclusion This study corroborates the notion that PNES share more similarities than differences cross-culturally and across international borders. However, the background determined by cultural, ethnic, and religious differences may influence the semiology of PNES. Further cross-cultural studies involving more than two continents may advance our understanding of PNES. Fil: Asadi Pooya, Ali A.. Shiraz University Of Medical Sciences; Irán. Thomas Jefferson University; Estados Unidos Fil: Valente, Kette. Universidade de Sao Paulo; Brasil Fil: Restrepo, Anilu Daza. La Trinidad Medical Center; Venezuela Fil: D`alessio, Luciana. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Homayoun, Maryam. Shiraz University of Medical Sciences; Irán Fil: Bahrami, Zahra. Shiraz University Of Medical Sciences; Irán Fil: Alessi, Rudá. Universidade de Sao Paulo; Brasil Fil: Paytan, Angélica Aroni. La Trinidad Medical Center; Venezuela Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Myers, Lorna. Northeast Regional Epilepsy Group; Estados Unidos Fil: Sawchuk, Tyson. Alberta Children's Hospital; Canadá. University of Nicosia; Chipre Fil: Buchhalter, Jeffrey. Alberta Children's Hospital; Canadá. University of Calgary; Canadá Fil: Taha, Firas. Northeast Regional Epilepsy Group; Estados Unidos Fil: Lazar, Lorraine M.. Northeast Regional Epilepsy Group; Estados Unidos Fil: Pick, Susannah. Kings' College London; Reino Unido Fil: Nicholson, Timothy. Kings' College London; Reino Unido

Purpose: We compared various clinical characteristics of pediatric-onset psychogenic nonepileptic seizures(PNES) between patients from fie countries. The purpose of this study was to advance our understanding ofpediatric-onset PNES cross-culturally.Methods: In this retrospective study, we compared consecutive patients with PNES with an age at onset of 16years and younger from epilepsy monitoring units in Iran, Brazil, the USA, Canada, and Venezuela. Age, gender,age at seizure onset, seizure semiology, predisposing factors, and video-EEG recordings of all patients wereextracted. Pearson Chi-Square, one-way ANOVA and Bonferroni correction tests were used for statistical analyses.Results: Two hundred twenty-nine patients were studied (83 from Iran, 50 from Brazil, 39 from Canada, 30 fromthe USA, and 27 from Venezuela). Mean age at the onset of seizures was 12.1 ± 3.2 years (range: 4?16 years).The sex ratio of the patients was 1.83: 1 (148 females and 81 males). Clinical characteristics of pediatric-onsetPNES showed some signifiant diffrences among the nations. However, factors associated with pediatric-onsetPNES in these fie nations were similar.Conclusion: This study underscores how international cross-cultural studies can make important contributions toour understanding of PNES. Patients with pediatric-onset PNES from diffrent countries were similar on manyrisk factors associated with PNES. This suggests universality in many features of PNES. However, intriguingdiffrences were also noted with regard to seizure semiology, which might be the result of cultural factors. Fil: Asadi Pooya, Ali A.. Universidad de Ciencias Médicas, Shiraz; Irán. Universidad Thomas Jefferson; Estados Unidos Fil: Myers, Lorna. Grupo regional de epilepsia del noreste; Estados Unidos Fil: Valente, Kette. Universidad de Sao Paulo; Brasil Fil: Sawchuk, Tyson. Hospital de niños de Alberta, Calgary; Canadá. Universidad de Nicosia; Chipre Fil: Daza Restrepo, Anilu. Centro Médico La Trinidad; Venezuela Fil: Homayouna, Maryam. Universidad de Ciencias Médicas, Shiraz; Irán Fil: Buchhalter, Jeffey. Universidad de Nicosia; Chipre. Universidad de Calgary; Canadá Fil: Bahramia, Zahra. Universidad de Ciencias Médicas, Shiraz; Irán Fil: Taha, Firas. Grupo regional de epilepsia del noreste; Estados Unidos Fil: Lazar, Lorraine M.. Grupo regional de epilepsia del noreste; Estados Unidos Fil: Aroni Paytan, Angélica. Centro Médico La Trinidad; Venezuela Fil: D`alessio, Luciana. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina; Argentina Fil: Alessi, Rudá. Universidad de Sao Paulo; Brasil Fil: Pick, Susannah. Instituto de Psiquiatría, Psicología y Neurociencia, King's College London; Reino Unido Fil: Nicholson, Timothy R.. Instituto de Psiquiatría, Psicología y Neurociencia, King's College London; Reino Unido

Objectives/Aims Catatonia is an important neuropsychiatric disorder with a high morbidity and mortality. However, due to a perception that it is very infrequent and because of the acuity of the patients, it has remained poorly studied and research has often been confined to small groups. We aimed to establish the demographic, disease-related variables and blood-based biomarkers for catatonia in a large dataset. Methods We used the Clinical Records Interactive Search (CRIS) system hosted at the NIHR Maudsley Biomedical Research Centre to search the clinical records for patients with catatonia. An initial free-text search was refined by use of a natural language processing app. The results of the app were validated by three of the authors, who included patients in the analysis only if a clinician had made a diagnosis of catatonia and two or more items of the Bush-Francis Catatonia Screening Instrument were in evidence. Demographics, disease-related variables and blood-based biomarkers could then be extracted for these patients and compared, where relevant, to non-catatonic psychiatric patients. Results The natural language processing app extracted the records of 2766 patients with at least one mention of catatonia in their records. The majority of cases identified by the app could be validated by the researchers. A high proportion of patients had more than one episode of catatonia. Full results will be available in time for the presentation. Conclusions This study demonstrates that catatonia is not very rare, even relying on clinician identification. The frequency of recurrence is interesting, as it suggests that catatonia might indicate an underlying trait, rather than merely a transient state.

ObjectiveThis study describes medication prescribing patterns in patients with motor functional neurological disorder (mFND) treated in South London and Maudsley NHS Foundation Trust (SLaM), comparing outcomes to a control group of psychiatric patients from the same hospital trust.MethodThis is a retrospective case-control study using a psychiatric case register. Cross-sectional data were obtained from 322 mFND patients and 644 psychiatry controls who had had contact with SLaM between 1st January 2006 and 31st December 2016.ResultsA slightly lower proportion of mFND patients received medication compared to controls (76.6% v. 83.4%, OR: 0.59, CI: 0.39–0.89, p p = 0.001) and had higher prescription rates of antidepressants, anti-epileptics, analgesics, and certain non-psychotropic medications. Higher numbers of prescriptions were associated with co-morbid physical conditions, and previous psychiatric admissions.ConclusionsThis is the first study to describe medication prescriptions in a large cohort of mFND patients. Patients were prescribed a wide range of psychiatric and physical health medications, with higher rates of polypharmacy than controls. Psychotropicmedication prescription is not necessarily the first line treatment for mFND, where physiotherapy and psychotherapy may be offered initially. There is limited, early-phase evidence for pharmacological therapies for mFND, and as such, the benefit-to-risk ratio of prescribing in this complex and poorly understood disorder should be carefully assessed.

BackgroundFunctional neurological disorder (FND), previously known as conversion disorder, is common and often results in substantial distress and disability. Previous research lacks large sample sizes and clinical surveys are most commonly derived from neurological settings, limiting our understanding of the disorder and its associations in other contexts. We sought to address this by analysing a large anonymised electronic psychiatric health record dataset.MethodsData were obtained from 322 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who had an ICD-10 diagnosis of motor FND (mFND) (limb weakness or disorders of movement or gait) between 1 January 2006 and 31 December 2016. Data were collected on a range of socio-demographic and clinical factors and compared to 644 psychiatric control patients from the same register.ResultsWeakness was the most commonly occurring functional symptom. mFND patients were more likely to be female, British, married, employed pre-morbidly, to have a carer and a physical health condition, but less likely to have had an inpatient psychiatric admission or to receive benefits. No differences in self-reported sexual or physical abuse rates were observed between groups, although mFND patients were more likely to experience life events linked to inter-personal difficulties.ConclusionsmFND patients have distinct demographic characteristics compared with psychiatric controls. Experiences of abuse appear to be equally prevalent across psychiatric patient groups. This study establishes the socio-demographic and life experience profile of this understudied patient group and may be used to guide future therapeutic interventions designed specifically for mFND.

AimsFunctional neurological disorder (FND), formerly known as conversion disorder, causes a high burden of disability and distress, and is amongst the most commonly encountered conditions in neurology clinics and neuropsychiatry services, yet the therapeutic evidence base is limited. Research into psychedelics such as psilocybin and lysergic acid diethylamide (LSD) is currently being undertaken with significant renewed interest, and in recent studies psychedelics have shown promise in treating a range of psychiatric conditions. Modification of neural circuits associated with self-representation is thought to underlie some of this effect, and as some contemporary theories of FND focus on aberrant somatic self-representation, psychedelics may therefore represent an unexplored treatment option for FND. METHODS: We systematically reviewed studies involving the use of psychedelics in FND. Nine studies published between 1954 – 1967, with a total of 26 patients, were identified. Due to restriction of licencing of psychedelic drugs since this period, no modern studies were identified.ResultsLSD was the most commonly used psychedelic, with some studies also using psilocybin and/or mescaline. The number of therapeutic sessions of psychotherapy ± psychedelic substance administration ranged from one to 26, with descriptions of therapeutic methods used widely varying, and in some cases not described in any detail. Psychedelics were given either orally or intramuscularly, with doses of LSD ranging from 25 to 2,000 micrograms (mcg), and doses of psilocybin ranging from 3 to 15 milligrams (mg). Of those treated, 69% (n=18) were found to have made at least some recovery, with 23% (n=6) having completely recovered after psychedelic therapy. Adverse events were typically mild and transient.ConclusionsStudies were generally of low quality, often lacking control groups and valid outcome measures. Despite this, the degree of improvement is considerable, even if the presumptive bias in favour of the treatment in the studies is taken into consideration. Furthermore, good therapeutic outcomes and lack of adverse events in modern open-label trials utilising psychedelic therapy for neuropsychiatric disorders is encouraging. Advances in the understanding of the neurobiology of FND, as well as further modern clinical research into the therapeutic utility of psychedelics, may help to determine whether psychedelics offer a feasible, safe and effective treatment for FND.

Objective/aimsInteroceptive differences have been proposed as an aetiological factor in functional neurological disorder (FND) but there is limited supportive evidence. Previous studies are few, have mixed findings and assessed only (objective) interoceptive accuracy, but not (metacognitive) interoceptive awareness. The aim of this study was to explore interoception in FND in greater detail, by assessing interoceptive accuracy and awareness in individuals with a range of FND presentations. As dissociative symptoms (e.g., depersonalisation, derealisation) are common in FND and could influence interoception, we sought to examine the effects of induced acute dissociation on interoception. We hypothesised that interoceptive accuracy/awareness would be impaired at baseline in FND relative to healthy controls, but that the differences would be exacerbated following dissociation induction.MethodsTwenty adults with FND were recruited from online FND support groups. Diagnosis was confirmed by medical documentation from a relevant healthcare professional. The FND group was compared to a group of 20 healthy controls recruited from online community groups. A modified heart-beat tracking task measured interoceptive accuracy (correct detection of heart beats) and awareness (confidence judgements). A control task involved counting visually presented geometric shapes. Both tasks were completed before and after a validated dissociation induction procedure (mirror-gazing).ResultsThe FND group reported elevated dissociation at baseline relative to controls (pConclusionsIndividuals with FND reported elevated dissociation both before and after a dissociation induction procedure, although this was exacerbated post-dissociation induction. In contrast, interoceptive accuracy was unimpaired at baseline, but impaired following dissociation induction, relative to controls. The FND group showed reduced metacognitive awareness for detection of bodily states and external (visual) stimuli. Future research should better determine the nature of interoceptive deficits in FND and assess the impact of dissociation on a range of cognitive and affective processes relevant to the disorder.

AimsFunctional neurological disorder (FND) is common and often severe. It is poorly understood, and there have been no international large-scale studies of self- management and illness beliefs in FND. We created a patient questionnaire to assess FND demographics, symptom comorbidity, self-management strategies (particularly in relation to prohibited substances), views on novel treatments, and illness beliefs.MethodsThe questionnaire was shared open access over a three-week period.Participants were recruited internationally through social media and patient groups. RESULTS: In total, 1162 respondents from 16 countries took the survey. Of these, 98% reported a formal diagnosis of FND from a consultant neurologist or other suitably trained clinician. Females constituted 86% of respondents, with an average age of 41.7 years (SD=12.50). Mean symptom duration was 7.69 years (SD=9.37) and average time from diagnosis was 2.24 years (SD=3.35), indicating a diagnostic lag of over 5 years. Symptom comorbidity was very high, with respondents reporting current: seizures (50%), gait disturbance (76%), loss of balance (77%), tremors (61%), muscle jerks/spasms (65%), altered sensations (79%), speech difficulties (65%), memory problems (80%), fatigue (93%), and headache (70%). Current psychiatric comorbidities – depression (43%), anxiety (51%), panic (20%), and PTSD (22%) - were also common. Illness beliefs varied, with respondents agreeing most strongly that FND is a combination of physical and stress/trauma-related factors. Respondents rated FND as having a severe effect on their life, with little control felt over their symptoms. Respondents had received a wide range of medical interventions, and many had tried alternative treatments. Prohibited substances such as cannabis, ketamine, and psychedelics had been used by 15% of respondents, with the majority experiencing no or minimal physical (90%) and psychological (95%) sequelae. Many respondents reported that they would be willing to try medically supervised psychedelic therapy if it was found to be safe and effective.ConclusionsThis large international online survey of FND patients indicated a striking co-occurrence of multiple symptoms. As expected, respondents reported that FND severely impacted on their lives, and many had lived with symptoms, which are not well managed by current medical therapies, for years. There was interest in novel putative treatments, such as medically supervised psychedelic therapies, which indicates a strong need to investigate alternative treatments for this poorly served patient group.

Objectives/AimsCatatonia is an important neuropsychiatric disorder with a high morbidity and mortality. However, due to a perception that it is very infrequent and because of the acuity of the patients, it has remained poorly studied and research has often been confined to small groups.We hypothesised that: catatonia would remain a significant clinical problem; catatonic patients would have a longer duration of admission and higher mortality; serum iron would be reduced, reflecting a systemic inflammatory response, and high rates of NMDA receptor antibody serum positivity would be observed.MethodsThis was a prospective cohort study that included patients in a large mental health trust who were diagnosed with catatonia between 2007 and 2016. We used the Clinical Records Interactive Search (CRIS) system hosted at the NIHR Maudsley Biomedical Research Centre to search the clinical records for patients with catatonia. An initial free-text search was refined by use of a natural language processing app. The results of the app were validated by three of the authors, who included patients in the analysis only if a clinician had made a diagnosis of catatonia and two or more items of the Bush-Francis Catatonia Screening Instrument were in evidence.Demographic, clinical and blood-based markers could then be extracted for these patients and compared, where relevant, to non-catatonic psychiatric patients.Results1,456 patients with catatonia (of whom 787 were psychiatric inpatients) and 37,456 psychiatric inpatient controls were identified. There was no evidence for a reduction in the rate of catatonia over time. Patients with catatonia were younger than the controls by 2.52 years (95% CI 1.30 to 3.73) and similar in gender composition. Patients with catatonia were more likely to be black (53.5% vs 24.5%, pConclusionsThis is the largest study of catatonia to date. There is evidence that catatonia is not dying out and confers high morbidity but without affecting mortality. The innate immune system does not seem to be activated, but NMDA receptor antibodies are present at higher rates than in psychiatric controls. We demonstrate that catatonia remains an important clinical problem and may be associated with neuroimmunological dysfunction.

BackgroundFND and migraine are both common disorders that occur in the absence of structural brain damage. Clinically, it is suspected that they might co- occur more often than would be expected by chance. It is important to distinguish them in some clinical situations, especially hemiplegic migraine from migraine that triggers FND with weakness but there are no systematic, and limited narrative reviews of the topic.ObjectivesTo study the association of FND and migraine with a systematic review of the literature.MethodsSearches for relevant literature were performed in July 2018 in MEDLINE and PsycINFO electronic databases without time limitation and augmented by hand searching the reference lists within these papers and the knowledge of literature from selected experts in the fieldResultsFive studies were identified; two from electronic, one from hand searches and two from experts. The total number of the sample size from the included studies was 2385. Findings generally indicated a positive association between migraine and FND. A prospective epidemiological study found that number of FND symptoms reported by migraineurs was 2.2 and 1.1 on controls. In a retrospective review of medical report study functional movement disorders occurred within 6 months or concomitantly with migraine onset in 71% of chronic migraine (CM) & 87.5% episodic migraine (EM) cases and the outcome effect of treating migraine on FND symptoms was a decrease or remission in 91% in CM and by 67% in EM. In a retrospective chart review study in the epilepsy monitoring unit, migraine diagnosis had a predictive value for diagnosing PNES & epilepsy OR=1.83, pConclusionsDespite a limited evidence base, migraine and FND appear to co-occur at elevated rates. It is imperative to explore how treating either migraine or FND impacts on the other. More studies are needed to confirm these findings and to investigate any potential mechanistic overlap.

We were very pleased to hear from a patient about their illness journey and agree that, when appropriate, uncertainty should be acknowledged by healthcare professionals and communicated to patients and their carers.1 Two of us (JC, TN) run specialist clinics for functional neurological disorders and one of us (KH) is the chief executive officer of a related charity (FND Action). We agree that a diagnosis …

PURPOSE: The purpose of the study was to review the literature on the terminologies for psychogenic nonepileptic seizures (PNES) and make a proposal on the terminology of this condition. This proposal reflects the authors' own opinions.METHODS: We systematically searched MEDLINE (accessed from PubMed) and EMBASE from inception to October 10, 2019 for articles written in English with a main focus on PNES (with or without discussion of other functional neurological disorders) and which either proposed or discussed the accuracy or appropriateness of PNES terminologies.RESULTS: The search strategy reported above yielded 757 articles; 30 articles were eventually included, which were generally of low quality. "Functional seizures" (FS) appeared to be an acceptable terminology to name this condition from the perspective of patients. In addition, FS is a term that is relatively popular with clinicians.CONCLUSION: From the available evidence, FS meets more of the criteria proposed for an acceptable label than other popular terms in the field. While the term FS is neutral with regard to etiology and pathology (particularly regarding whether psychological or not), other terms such as "dissociative", "conversion", or "psychogenic" seizures are not. In addition, FS can potentially facilitate multidisciplinary (physical and psychological) management more than other terms. Adopting a universally accepted terminology to describe this disorder could standardize our approach to the illness and facilitate communication between healthcare professionals, patients, their families, carers, and the wider public.

Functional neurological disorder (FND), formerly known as conversion disorder, causes a high burden of disability and distress, and is amongst the most commonly encountered conditions in neurology clinics and neuropsychiatric services, yet the therapeutic evidence base is somewhat limited. There has been recent interest in the therapeutic potential of psychedelics such as psilocybin and lysergic acid diethylamide (LSD), and in recent studies psychedelics have shown promise in treating a range of neuropsychiatric conditions. Modification of neural circuits associated with self-representation is thought to underlie some of this effect, and as some contemporary theories of FND focus on aberrant somatic self-representation, psychedelics may therefore represent an unexplored treatment option for FND. We systematically reviewed studies involving the use of psychedelics in FND. Nine studies published between 1954 and 1967, with a total of 26 patients, were identified. Due to restriction of licencing of psychedelic drugs since this period, no modern studies were identified. In most cases, patients received a course of psychotherapy with variable adjunctive administration of psychedelics (in a combination known as ‘psycholytic therapy’), with protocols varying between studies. Of those treated, 69% ( n = 18) were found to have made at least some recovery on heterogeneous and subjective clinician-rated criteria. Adverse events were mostly mild and transient; however, at least one patient terminated the study due to distressing effects. All included studies were of low quality, often lacking control groups and valid outcome measures. Although no conclusions on efficacy may be drawn from these data, further research may help to determine whether psychedelics offer a feasible, safe and effective treatment for FND.

Purpose Previous studies from a few countries have reported semiological differences in younger children compared with adolescents or adults with psychogenic nonepileptic seizures (PNESs). This study tested the hypothesis that semiological, demographic, and historical risk factors vary with different ages of PNES onset in a large cohort from different countries. Methods In this retrospective study, we investigated patients consecutively referred for PNES, who were admitted to epilepsy monitoring units in Iran, Brazil, Venezuela, Canada, Argentina, and USA. Age, gender, age at seizure onset, seizure semiology, and factors predisposing to PNES (abuse, stressors) were documented according to routine diagnostic practices at each center. Participants were grouped according to their age at onset (i.e., childhood, adolescence, or adulthood). Results A total of 448 patients were studied. Female predominance was associated with adolescent- (85/122, 70%) and adult-onset (190/270, 70%) but not in childhood-onset PNES (28/56, 50%) (p = 0.011). Event frequency in the month preceding the diagnosis was higher in the childhood- [ x ¯ = 50, standard deviation (sd) = 82, p = 0.025] versus adolescent- ( x ¯ = 24, sd = 36) or adult-onset groups ( x ¯ = 29, sd = 61). Significant between-group differences were observed for generalized body movements (p = 0.0001) and ictal injury (p = 0.027), suggesting more severe ictal presentations in adult-onset PNES compared with younger ages. Adult-onset patients were also more likely to be taking an unnecessary antiepileptic medication (p = 0.010). Conclusion While PNES may present at any age, there appear to be notable differences across the lifespan with respect to some of the clinical characteristics. Further international and cross-cultural studies may reveal other interesting characteristics of PNES.

Functional neurological disorder (FND) is a common and highly disabling disorder, but its aetiology remains enigmatic. Conceptually, there has been reduced emphasis on the role of psychosocial stressors in recent years, with a corresponding increase in neurobiological explanations. However, a wealth of evidence supports the role of psychosocial adversities (eg, stressful life events, interpersonal difficulties) as important risk factors for FND. Therefore, there is a need to integrate psychosocial (environmental) and neurobiological factors (eg, sensorimotor and cognitive functions) in contemporary models of FND. Altered emotional processing may represent a key link between psychosocial risk factors and core features of FND. Here, we summarise and critically appraise experimental studies of emotional processing in FND using behavioural, psychophysiological and/or neuroimaging measures in conjunction with affective processing tasks. We propose that enhanced preconscious (implicit) processing of emotionally salient stimuli, associated with elevated limbic reactivity (eg, amygdala), may contribute to the initiation of basic affective/defensive responses via hypothalamic and brainstem pathways (eg, periaqueductal grey). In parallel, affect-related brain areas may simultaneously exert a disruptive influence on neurocircuits involved in voluntary motor control, awareness and emotional regulation (eg, sensorimotor, salience, central executive networks). Limbic-paralimbic disturbances in patients with FND may represent one of several neurobiological adaptations linked to early, severe and/or prolonged psychosocial adversity. This perspective integrates neurobiological and psychosocial factors in FND and proposes a research agenda, highlighting the need for replication of existing findings, multimodal sampling across emotional response domains and further examination of emotional influences on sensorimotor and cognitive functions in FND populations.

Importance: Functional neurological disorders (FND) are common sources of disability in medicine. Patients have often been misdiagnosed, correctly diagnosed after lengthy delays, and/or subjected to poorly delivered diagnoses that prevent diagnostic understanding and lead to inappropriate treatments, iatrogenic harm, unnecessary and costly evaluations, and poor outcomes. Observations: Functional Neurological Symptom Disorder/Conversion Disorder was adopted by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, replacing the term psychogenic with functional and removing the criterion of psychological stress as a prerequisite for FND. A diagnosis can now be made in an inclusionary manner by identifying neurological signs that are specific to FNDs without reliance on presence or absence of psychological stressors or suggestive historical clues. The new model highlights a wider range of past sensitizing events, such as physical trauma, medical illness, or physiological/psychophysiological events. In this model, strong ideas and expectations about these events correlate with abnormal predictions of sensory data and body-focused attention. Neurobiological abnormalities include hypoactivation of the supplementary motor area and relative disconnection with areas that select or inhibit movements and are associated with a sense of agency. Promising evidence has accumulated for the benefit of specific physical rehabilitation and psychological interventions alone or in combination, but clinical trial evidence remains limited. Conclusions and Relevance: Functional neurological disorders are a neglected but potentially reversible source of disability. Further research is needed to determine the dose and duration of various interventions, the value of combination treatments and multidisciplinary therapy, and the therapeutic modality best suited for each patient.

Item does not contain fulltext Background: Stressful life events and maltreatment have traditionally been considered crucial in the development of conversion (functional neurological) disorder, but the evidence underpinning this association is not clear. We aimed to assess the association between stressors and functional neurological disorder. Methods: We systematically reviewed controlled studies reporting stressors occurring in childhood or adulthood, such as stressful life events and maltreatment (including sexual, physical abuse, and emotional neglect) and functional neurological disorder. We did a meta-analysis, with assessments of methodology, sources of bias, and sensitivity analyses. Findings: 34 case-control studies, with 1405 patients, were eligible. Studies were of moderate-to-low quality. The frequency of childhood and adulthood stressors was increased in cases compared with controls. Odds ratios (OR) were higher for emotional neglect in childhood (49% for cases vs 20% for controls; OR 5·6, 95% CI 2·4-13·1) compared with sexual abuse (24% vs 10%; 3·3, 2·2-4·8) or physical abuse (30% vs 12%; 3·9, 2·2-7·2). An association with stressful life events preceding onset (OR 2·8, 95% CI 1·4-6·0) was stronger in studies with better methods (interviews; 4·3, 1·4-13·2). Heterogeneity was significant between studies (I2 21·1-90·7%). 13 studies that specifically ascertained that the participants had not had either severe life events or any subtype of maltreatment all found a proportion of patients with functional neurological disorder reporting no stressor. Interpretation: Stressful life events and maltreatment are substantially more common in people with functional neurological disorder than in healthy controls and patient controls. Emotional neglect had a higher risk than traditionally emphasised sexual and physical abuse, but many cases report no stressors. This outcome supports changes to diagnostic criteria in DSM-5; stressors, although relevant to the cause in many patients, are not a core diagnostic feature. This result has implications for ICD-11. Funding: None. 14 p.

Background Urethral strictures can be difficult to diagnose at an early stage because the urinary flow rate does not diminish until the urethral calibre is ≤3mm. In the past, posturethral surgery follow-up has relied upon flow rates and contrast imaging. Objective To evaluate the role of flexible urethroscopy in the follow-up of patients undergoing urethroplasty. Design, setting, and participants Prospective flexible urethroscopy follow-up of 144 male patients who underwent urethroplasty by a single surgeon over a 10-yr period at a tertiary referral centre. Intervention Flexible urethroscopy at 3, 6, and 12 mo postoperatively, and annually thereafter. Outcome measurements and statistical analysis Type of recurrence, based on urethroscopy findings, and further interventions were measured. Actuarial analysis was performed using Kaplan-Meier curves and a log-rank test. Results and limitations All 144 patients underwent flexible urethroscopy follow-up over a median postoperative follow-up of 22 mo (range: 1–96 mo). No further intervention was required for 117 patients (81.25%); 27 (18.75%) developed recurrences that required further treatment. Recurrences included diaphragms (13 patients) or significant restenosis (14 patients). Diaphragms were treated by urethrotomy, gentle dilatation, or a short course of intermittent self-dilatation. Restenosis required repeated simple procedures or surgical revision. Most recurrences (26 of 27, 96%) were detected within the first year. Urinary peak flow-rate data were available for 11 of 27 of these recurrences; 7 patients had flow rates >15ml/s. Anastomotic procedures had greater success than augmentation urethroplasty ( p =0.0136); there was no significant difference in outcomes between redo and non-redo surgery ( p =0.2093) Conclusions Endoscopic follow-up of patients after urethroplasty enables earlier identification and treatment of recurrences compared to the use of urinary flow rates alone. It also enables the identification of two different morphologic recurrence patterns that require different types of intervention. Patient summary Endoscopy detects most stricture recurrences within 1 yr after urethroplasty and is more sensitive than using urinary flow rates alone.

Purpose Sex-related differences have been reported in patients with neurological and psychiatric disorders. It is also plausible to assume that there might be differences between females and males with psychogenic nonepileptic seizures (PNES). Methods In this retrospective study, we investigated patients with PNES, who were admitted to the epilepsy monitoring units at centers in Iran, the USA, Canada, Brazil, Argentina, and Venezuela. Age, sex, age at seizure onset, seizure semiology, factors potentially predisposing to PNES, and video-electroencephalography recording of all patients were registered routinely. Results Four hundred and fifty-one patients had PNES-only and were eligible for inclusion; 305 patients (67.6%) were females. We executed a logistic regression analysis, evaluating significant variables in univariate analyses (i.e., age, age at onset, aura, presence of historical sexual or physical abuse, and family dysfunction). The only variables retaining significance were historical sexual abuse (p = 0.005) and presence of aura (p = 0.01); physical abuse was borderline significant (p = 0.05) (all three were more prevalent among females). Conclusion Similarities between females and males outweigh the differences with regard to the demographic and clinical characteristics of PNES. However, notable differences are that females more often report lifetime adverse experiences (sexual and probably physical abuse) and auras. While social, psychological, and genetic factors may interact with lifetime adverse experiences in the inception of PNES, the link is not yet clear. This is an interesting avenue for future studies. Fil: Asadi Pooya, Ali A.. Shiraz University of Medical Sciences; Irán. Thomas Jefferson University; Estados Unidos Fil: Myers, Lorna. Northeast Regional Epilepsy Group; Estados Unidos Fil: Valente, Kette Dualibi Ramos. Universidade de Sao Paulo; Brasil Fil: Daza Restrepo, Anilu. La Trinidad Medical Center; Venezuela Fil: D`alessio, Luciana. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Sawchuk, Tyson. Alberta Children's Hospital; Canadá. University of Nicosia; Chipre Fil: Homayoun, Maryam. Shiraz University of Medical Sciences; Irán Fil: Bahrami, Zahra. Shiraz University of Medical Sciences; Irán Fil: Alessi, Rudá. Universidade de Sao Paulo; Brasil Fil: Paytan, Angélica Aroni. La Trinidad Medical Center; Venezuela Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Buchhalter, Jeffrey. Alberta Children's Hospital; Canadá. University of Calgary; Canadá Fil: Taha, Firas. Northeast Regional Epilepsy Group; Estados Unidos Fil: Lazar, Lorraine M.. Northeast Regional Epilepsy Group; Estados Unidos Fil: Pick, Susannah. Kings' College London; Reino Unido Fil: Nicholson, Timothy. Kings' College London; Reino Unido

Nitrites in Acute Myocardial Infarction Nishat Siddiqi1, Margaret Bruce1, Christopher J. Neil1, Graeme MacLennan2, Seonaidh Cotton2, Sofia A. Papadopoulou3, Baljit Jagpal1, Sue Brown3, Fatima Perez Gonzalez3, Satnam Singh1, Konstantin Schwarz1, Martin Feelisch4, Nicholas Bunce5, Pitt O Lim5, David Hildick-Smith6, John Horowitz7, Melanie Madhani8, Nicholas Boon9, Dana Dawson10, Juan-Carlos Kaski3, Michael P Frenneaux10. 1Dept of Cardiovascular Rsch, Univ of Aberdeen, Aberdeen, United Kingdom, 2Health Sciences Building (third floor), Centre for Healthcare Randomised Trials (CHaRT), Aberdeen, United Kingdom, 3Cardiovascular Sciences Rsch Centre, St George’s Univ of London, London, United Kingdom, 4Faculty of Medicine, Univ of Southampton, Southampton, 5Cardiology Dept, St George’s Healthcare NHS Trust, 6Cardiology Research Unit, Brighton and Sussex Univ Hospitals, Brighton, United Kingdom, 7Basil Hetzel Unit for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, 8Centre for Cardiovascular Sciences, Univ of Birmingham, Birmingham, United Kingdom, 9Centre for Cardiovascular Sciences, Univ of Edinburgh, Edinburgh, United Kingdom, 10School of Medicine and Dentistry, Univ of Aberdeen, Aberdeen Introduction :Despite reperfusion therapy for acute myocardial infarction (AMI), heart failure remains a major sequel. Reperfusion leads to further damage, described as ischemia-reperfusion-injury (IRI). This contributes up to 50% of the final infarct size. In pre-clinical models nitrite potently protects against IRI in the heart and other organs. Hypothesis :Intravenous (iv) sodium nitrite, administered immediately before opening of the infarct-related artery, results in significant reduction of IRI in patients with acute ST elevation MI (STEMI). Methods :In this phase II, randomised, placebo-controlled, double-blind, multicentre trial, 220 patients with first acute STEMI and TIMI 0 or 1 flow were randomised …

BackgroundAnti-N-methyl-d-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a ‘purely’ psychotic illness without overt neurological symptoms.MethodWe conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis.ResultsSeven studies were included, comprising 1441 patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69–9.50] were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94–2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used.ConclusionsA minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.