Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study.

BACKGROUND: Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin. METHODS: Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray. RESULTS: The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days). CONCLUSIONS: The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.

Clinical predictors of encephalitis in UK adults-A multi-centre prospective observational cohort study.

OBJECTIVES: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. METHODS: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. RESULTS: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had HSV, 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5-50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45-250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. CONCLUSIONS: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy.

Increased volume of cerebral oedema is associated with risk of acute seizure activity and adverse neurological outcomes in encephalitis - regional and volumetric analysis in a multi-centre cohort.

BACKGROUND: Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), and many suffer from poor long-term neurological sequelae. Establishing factors associated with acute seizures risk and poor outcomes could support clinical care. We aimed to conduct regional and volumetric analysis of cerebral oedema on magnetic resonance imaging (MRI) in patients with AES. We assessed the relationship of brain oedema with acute seizure activity and long-term neurological outcome. METHODS: In a multi-centre cohort study, adults and children presenting with an AES were recruited in the UK. The clinical and brain MRI data were retrospectively reviewed. The outcomes variables were inpatient acute seizure activity and neurological disability at six-months post-discharge. A poor outcome was defined as a Glasgow outcome score (GOS) of 1-3. We quantified regional brain oedema on MRI through stereological examination of T2-weighted images using established methodology by independent and blinded assessors. Clinical and neuroimaging variables were analysed by multivariate logistic regression to assess for correlation with acute seizure activity and outcome. RESULTS: The study cohort comprised 69 patients (mean age 31.8 years; 53.6% female), of whom 41 (59.4%) had acute seizures as inpatients. A higher Glasgow coma scale (GCS) score on admission was a negative predictor of seizures (OR 0.61 [0.46-0.83], p = 0.001). Even correcting for GCS on admission, the presence of cortical oedema was a significant risk factor for acute seizure activity (OR 5.48 [1.62-18.51], p = 0.006) and greater volume of cerebral oedema in these cortical structures increased the risk of acute seizures (OR 1.90 [1.12-3.21], p = 0.017). At six-month post-discharge, 21 (30.4%) had a poor neurological outcome. Herpes simplex virus encephalitis was associated with higher risk of poor outcomes in univariate analysis (OR 3.92 [1.08-14.20], p = 0.038). When controlling for aetiology, increased volume of cerebral oedema was an independent risk factor for adverse neurological outcome at 6 months (OR 1.73 [1.06-2.83], p = 0.027). CONCLUSIONS: Both the presence and degree of cerebral oedema on MRIs of patients with AES may help identify patients at risk of acute seizure activity and subsequent long-term morbidity.

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts.

Objective: In patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model. Methods: We analysed 203 patients from 24 English hospitals (2005-2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013-2016) (Cohort 2). Results: In Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025).A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001). Conclusion: Age, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis.

Clinical management of community-acquired meningitis in adults in the UK and Ireland in 2017: a retrospective cohort study on behalf of the National Infection Trainees Collaborative for Audit and Research (NITCAR).

OBJECTIVES: To assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland. DESIGN: Retrospective cohort study. SETTING: 64 UK and Irish hospitals. PARTICIPANTS: 1471 adults with community-acquired meningitis of any aetiology in 2017. RESULTS: None of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3-9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10). CONCLUSION: This study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.

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

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

What do people hospitalised with COVID-19 think about their care? Results of a satisfaction survey during the first wave of COVID-19 in Liverpool.

Despite huge advances in vaccines, testing and treatments for COVID-19, there is negligible evidence on the perceptions of people hospitalised with COVID-19 about the care they received. To address this, we developed a satisfaction survey for people with COVID-19 admitted to our hospital during the first COVID-19 wave in Liverpool. Of those invited, 98/160 (61%) responded, of whom 94/98 (96%) completed the survey. Respondents rated overall care highly (mean 4.7/5) and 89/94 (95%) reported that they would recommend the hospital to friends and/or family. Most respondents felt safe on the ward (94%), with privacy maintained (93%) and pain well managed (90%). Fewer than two-thirds (63%) of respondents considered themselves adequately consulted regarding medications and side effects. Sleep and food/drink quality were also highlighted as areas for improvement. To overcome the issues raised, we generated a 'COVID-19 practice pointers' poster within an integrated educational bundle on COVID-19 wards. The impact of the bundle on perceptions of people hospitalised with COVID-19 will be evaluated in people hospitalised with COVID-19 in Liverpool in 2021. Whether hospitalised for COVID-19 or other conditions, our survey results are a timely reminder of the importance of involving patients in shaping the care that they receive.

A patient satisfaction survey and educational package to improve the care of people hospitalised with COVID-19: a quality improvement project, Liverpool, UK.

Background: The perspectives and experiences of people hospitalised with COVID-19 have been under-reported during the coronavirus pandemic. We developed and conducted a COVID-19 patient satisfaction survey in a large university-affiliated secondary healthcare centre in Liverpool, UK, during Europe's first coronavirus wave (April-June 2020). The survey found that care was rated highly, including among people of Black Asian and Minority Ethnic (BAME) background. However, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement.   Methods: To improve care for people with COVID-19 admitted to our centre, we designed an educational package for healthcare professionals working on COVID-19 wards. The package, implemented in August 2020, included healthcare worker training sessions on providing holistic care and placement of "Practice Pointers" posters. Patient satisfaction was re-evaluated during the second/third COVID-19 waves in Liverpool (September 2020 - February 2021). Results: Across waves, most (95%) respondents reported that they would recommend our hospital to friends and/or family and rated overall care highly. Comparison of the responses of second/third-wave respondents (n=101) with first-wave respondents (n=94) suggested improved patient satisfaction across most care domains but especially those related to having worries and fears addressed and being consulted about medications and their side-effects. Conclusions: People admitted with COVID-19 to our centre in Liverpool, including those from BAME background, rated the care they received highly. A simple education package improved the feedback on care received by respondents between the first and second/third waves. These UK-first findings are informing regional strategies to improve person-centred care of hospitalised people with COVID-19.

Neurological associations of COVID-19.

BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. RECENT DEVELOPMENTS: A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. WHERE NEXT?: Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study.

OBJECTIVES: Our aim was to compare neuropsychological and psychiatric outcomes across three encephalitis aetiological groups: Herpes simplex virus (HSV), other infections or autoimmune causes (Other), and encephalitis of unknown cause (Unknown). METHODS: Patients recruited from NHS hospitals underwent neuropsychological and psychiatric assessment in the short-term (4 months post-discharge), medium-term (9-12 months after the first assessment), and long-term (>1-year). Healthy control subjects were recruited from the general population and completed the same assessments. RESULTS: Patients with HSV were most severely impaired on anterograde and retrograde memory tasks. In the short-term, they also showed executive, IQ, and naming deficits, which resolved in the long-term. Patients with Other or Unknown causes of encephalitis showed moderate memory impairments, but no significant impairment on executive tests. Memory impairment was associated with hippocampal/medial temporal damage on magnetic resonance imaging (MRI), and naming impairment with left temporal and left frontal abnormalities. Patients reported more subjective cognitive complaints than healthy controls, with tiredness a significant problem, and there were high rates of depression and anxiety in the HSV and the Other encephalitis groups. These subjective, self-reported complaints, depression, and anxiety persisted even after objectively measured neuropsychological performance had improved. CONCLUSIONS: Neuropsychological and psychiatric outcomes after encephalitis vary according to aetiology. Memory and naming are severely affected in HSV, and less so in other forms. Neuropsychological functioning improves over time, particularly in those with more severe short-term impairments, but subjective cognitive complaints, depression, and anxiety persist, and should be addressed in rehabilitation programmes.

'More than devastating'-patient experiences and neurological sequelae of Japanese encephalitis§.

BACKGROUND: Japanese encephalitis (JE), caused by the mosquito-borne JE virus, is a vaccine-preventable disease endemic to much of Asia. Travellers from non-endemic areas are susceptible if they travel to a JE endemic area. Although the risk to travellers of JE is low, the consequences may be severe. METHODS: Here, we describe three cases of JE in British travellers occurring in 2014-15. In addition, we report, through interviews with survivors and their families, personal experiences of life after JE. RESULTS: Three cases of JE were diagnosed in British travellers in 2014/15. One was acquired in Thailand, one in China and one in either Thailand, Laos or Cambodia. All three patients suffered severe, life-threatening illnesses, all were admitted to intensive care units and required medical evacuation back to the UK. One patient suffered a cardiac arrest during the acute stage but made a good recovery. The other two patients remain significantly paralysed and ventilator dependent. All three cases had clear indications for vaccination, and all have been left with life-changing neurological sequelae. CONCLUSIONS: Travel health providers should be aware of the severity of JE, as well as the risk, allowing travellers to make fully informed decisions on JE vaccination.

Understanding parental perspectives on outcomes following paediatric encephalitis: A qualitative study.

BACKGROUND: Encephalitis, characterised as inflammation of the brain tissue, is an important cause of acquired brain injury in children. Objective clinical outcomes vary significantly between affected patients, however they do not always correlate with quality of life as reported by parents. The aim of this study was to explore how parents experience and interpret outcomes in relation to their child who has been affected by encephalitis. METHODS: Data were derived from in-depth, semi-structured interviews, with 15 parents of 12 children and young people affected by encephalitis. Paediatric cases were identified from the retrospective arm of the research programme 'ENCEPH-UK-Understanding and Improving the Outcome of Encephalitis', and from the prospective UK childhood meningitis and encephalitis cohort study (UK-ChiMES, 2012 to 2016). Data were analysed thematically. RESULTS: Parents' perspectives on important outcomes for their child and family changed during the different stages of the encephalitis illness trajectory: from acute illness, recovery and rehabilitation, then reintegration into everyday life. Parents' understanding of their children's overall outcome was informed by their own experiences, involving comparisons with other children and reflections on their child's problems before, during and after the acute illness. CONCLUSION: Outcomes in paediatric encephalitis need to be understood in terms of the context of the patient and family experience as well as the timeframe of recovery. The research highlights the need to include more patient, parent and/or carer reported outcome measures during patient assessment, and that assessment should be repeated during recovery as family concerns change. In the longer term, these parameters could be included in clinical and rehabilitation practice to further support child recovery.

A pragmatic cluster randomised controlled trial of a tailored intervention to improve the initial management of suspected encephalitis.

OBJECTIVE: To determine whether a tailored multifaceted implementation strategy improves the initial management of patients with suspected encephalitis. DESIGN: Pragmatic two arm cluster randomised controlled trial. SETTING: Hospitals within the United Kingdom. PARTICIPANTS: Twenty-four hospitals nested within 12 postgraduate deaneries. Patients were identified retrospectively by searching discharge, microbiology, radiology and pharmacy records and included if they met clinical criteria or had a recorded suspicion of encephalitis. INTERVENTION: An implementation strategy designed to overcome barriers to change, comprising local action planning, education and training, feedback on performance, a lumbar puncture pack and a range of optional components. OUTCOMES: The primary outcome was the proportion of patients with suspected encephalitis undergoing diagnostic lumbar puncture within 12 hours of admission and starting aciclovir treatment within six hours. Secondary outcomes included the proportions of adults and children who had a lumbar puncture, who had appropriate cerebrospinal fluid investigations, and who had appropriate radiological imaging within 24 hours of admission. Data were collected from patient records for 12 months before and 12 months during the intervention period, and analysed blind to allocation. RESULTS: 13 hospitals were randomised to intervention and 11 to control (no intervention), with 266 and 223 patients with suspected encephalitis identified respectively. There was no significant difference in primary outcome between intervention and control hospitals (13.5% and 14.8% respectively, p = 0.619; treatment effect -0.188, 95% confidence interval -0.927 to 0.552), but both had improved compared to pre-intervention (8.5%). CONCLUSION: The improvement in both intervention and control arms may reflect overall progress in management of encephalitis through wider awareness and education. TRIAL REGISTRATION: Controlled Trials: ISRCTN06886935.

Care beyond the hospital ward: understanding the socio-medical trajectory of herpes simplex virus encephalitis.

BACKGROUND: Herpes simplex virus (HSV) encephalitis is a life-threatening infection of the brain, which has significant physical, cognitive and social consequences for survivors. Despite increasing recognition of the long-term effects of encephalitis, research and policy remains largely focused on its acute management, meaning there is little understanding of the difficulties people face after discharge from acute care. This paper aims to chart the problems and challenges which people encounter when they return home after treatment for HSV encephalitis. METHODS: The paper reports on data from 30 narrative interviews with 45 people affected by HSV encephalitis and their significant others. The study was conducted as part of the ENCEPH-UK programme grant on Understanding and Improving the Outcome of Encephalitis. RESULTS: The findings show the diverse challenges which are experienced by people after treatment for HSV encephalitis. We first chart how peoples' everyday lives are fragmented following their discharge from hospital. Second, we document the social consequences which result from the longer-term effects of encephalitis. Finally, we show how the above struggles are exacerbated by the lack of support systems for the post-acute effects of encephalitis, and describe how people are consequently forced to devise their own care routines and strategies for managing their problems. CONCLUSION: The paper argues that in order to improve long-term outcomes in encephalitis, it is vital that we develop pathways of support for the condition beyond the acute hospital setting. We conclude by making recommendations to enhance communication and care for the post-acute consequences of encephalitis, to ensure those affected are fully supported through the chronic effects of this devastating disease.

A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

OBJECTIVES: To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. METHODS: The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. RESULTS: Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. CONCLUSIONS: This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.

Diagnostic Pathways as Social and Participatory Practices: The Case of Herpes Simplex Encephalitis.

Herpes simplex virus (HSV) encephalitis is a potentially devastating disease, with significant rates of mortality and co-morbidities. Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease. In response, National Clinical Guidelines have been produced for the UK which make recommendations for improving the management of suspected viral encephalitis. However, little is currently known about the everyday experiences and processes involved in the diagnosis and care of HSV encephalitis. The reported study aimed to provide an account of the diagnosis and treatment of HSV encephalitis from the perspective of people who had been affected by the condition. Thirty narrative interviews were conducted with people who had been diagnosed with HSV encephalitis and their significant others. The narrative accounts reveal problems with gaining access to a diagnosis of encephalitis and shortfalls in care for the condition once in hospital. In response, individuals and their families work hard to obtain medical recognition for the problem and shape the processes of acute care. As a consequence, we argue that the diagnosis and management of HSV encephalitis needs to be considered as a participatory process, which is co-produced by health professionals, patients, and their families. The paper concludes by making recommendations for developing the current management guidelines by formalising the critical role of patients and their significant others in the identification, and treatment of, HSV encephalitis.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis In A Young Child With Histological Evidence On Brain Biopsy Of Coexistent Herpes Simplex Virus Type 1 Infection.

We report a 3-year-old boy with anti-N-methyl-D-aspartate receptor encephalitis with a typical syndrome of movement disorder and encephalopathy and evidence of herpes simplex virus (HSV) type 1 infection on brain biopsy. HSV type 1 infection and anti-N-methyl-D-aspartate receptor encephalitis are temporally linked in some cases: this case suggests that prodromal HSV type-1 infection may be clinically subtle and easily missed.

Performing lumbar punctures for suspected CNS infections: experience and practice of trainee doctors.

Lumbar punctures are essential in the management of suspected CNS infections. However, despite clear guidelines their use can be haphazard. This survey investigated the training, knowledge and experience of UK doctors in training in relation to lumbar punctures.