Angela Vincent

Background:There are data suggesting that intravenous immunoglobulin treatment has some benefit for certain forms of encephalitis but robust evidence from large randomised controlled trials in children with all-cause encephalitis is lacking.Objective:To evaluate whether intravenous immunoglobulin treatment improves neurological outcomes in childhood encephalitis when given early in the illness.Design:Phase 3b, investigator-initiated, randomised, double-blind, placebo-controlled trial of intravenous immunoglobulin for the treatment of encephalitis in children.Setting:Twenty-one NHS Hospitals in the UK.Participants:Children aged 6 months to 16 years with a diagnosis of acute or sub-acute encephalitis.Intervention:Two doses (1 g/kg/dose) of either intravenous immunoglobulin or matching placebo, given 24–36 hours apart, in addition to standard treatment.Main outcome measure:Participants were followed up …

The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national longitudinal study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after admission. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.

The original version of this article omitted three members of the COVID-CNS Consortium. Alex Berry and Obioma Orazulume, who are from the ‘University College London, London, UK’, and Ian Galea, who is from the ‘University of Southampton, Southampton, UK’were added to the list of COVID-CNS Consortium members. This has been corrected in both the PDF and HTML versions of the article.

Dataset for the article: Clinical predictors of encephalitis in UK adults–A multi-centre prospective observational cohort study - LSTM Online Archive Liverpool School of Tropical Medicine logo LSTM Home > LSTM Research > LSTM Online Archive Login >Archive Home >About >Policies >Latest Additions >Search >Browse >Statistics >Help for Depositors Dataset for the article: Clinical predictors of encephalitis in UK adults–A multi-centre prospective observational cohort study Tools + Tools Defres, Sylviane, Tharmaratnam, Kukatharmini, Michael, Benedict D., Ellul, Mark, Davies, Nicholas WS, Easton, Ava, Griffiths, Michael J., Bhojak, Maneesh, Das, Kumar, Hardwick, Hayley, Cheyne, Chris, Kneen, Rachel, Medina-Lara, Antonieta, Salter, Anne Christine, Beeching, Nicholas J., Carrol, Enitan, Vincent, Angela, Garcia-Finana, Marta and Solomon, Tom (2023) Dataset for the article: Clinical predictors of encephalitis in UK …

N-methyl-d-aspartate (NMDA) receptor antibody encephalitis, since its description in 2007, has emerged as one of the most common causes of encephalitis among young people in the developed world [1]. While up to a third of cases of NMDA receptor antibody encephalitis are associated with an ovarian teratoma, the aetiology of the majority of cases remains unknown [2]. However, case reports of NMDA receptor antibody encephalitis occurring in the context of infection with Haemophilus influenzae, human herpesvirus 6, mumps virus, Enterovirus, Mycoplasma pneumoniae and Japanese encephalitis virus have been reported [3, 4], but the most robust association is with herpes simplex encephalitis, which one study found to be followed within a year byNMDA receptor antibody encephalitis in 18% of individuals [5]. There is also evidence of an association between NMDA receptor antibodies in serum and …

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor (fAChR) can lead to arthrogryposis multiplex congenita (AMC) and milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full fAChR-associated spectrum is still poorly understood. Here we report clinical and immunological data from a multicenter cohort (n=46 cases) associated with maternal fAChR antibodies. Remarkably, in 50% of mothers there was no previously established MG diagnosis. Offspring death occurred in 11/46 (23.9%), mainly antenatally. Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors …

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.

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All …