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

Backman, Ruth; Foy, Robbie; Diggle, Peter J.; Kneen, Rachel; Easton, Ava; Defres, Sylviane; McGill, Fiona; Michael, Benedict; Solomon, Tom

doi:10.1371/journal.pone.0202257

Cited by 6 publications

(4 citation statements)

References 51 publications

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“…Survivors of pediatric encephalitis demonstrate long-term neurological sequelae ranging from neurocognitive impairments and related learning challenges to behavioral and personality changes. 64 , 65 , 66 A 2016 meta-analysis found that a nearly half of the children who recover from viral encephalitis demonstrate ongoing neurodevelopmental impairments. 7 Long-term sequelae included developmental delay (35%), behavior problems (18%), intellectual impairments (17.6%), and motor deficits (18%).…”

Section: Discussionmentioning

confidence: 99%

Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance

Singer

Evankovich

Fisher

et al. 2021

Pediatric Neurology

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Background The objective of this study was to describe the case literature of human coronavirus infections in the nervous system of children, including from SARS-CoV-2, and to provide guidance to pediatric providers for managing the potential long-term effects on neurodevelopment of human coronavirus infections in the nervous system. Methods Using a structured strategy, the PubMed and Ovid:Embase databases were queried for articles about the clinical presentation and pathophysiology of coronavirus infections in the nervous system of children and young adults, aged 0 to 24 years. Results Of 2302 articles reviewed, 31 described SARS-CoV-2 infections in the nervous system of children and 21 described other human coronaviruses: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1. Excepting MERS-CoV, we found cases of neurological disease in children from each human coronavirus. Children with non-SARS-CoV-2 infections have suffered acute flaccid paralysis, acute disseminated encephalomyelitis, encephalitis, and seizures. In addition, cases of ischemic, hemorrhagic, and microvascular strokes have occurred in children with SARS-CoV-2. Patients with multisystem inflammatory syndrome in children have suffered encephalitis, stroke, pseudotumor cerebri syndrome, and cytotoxic lesions of deep brain structures. Despite these reports, few articles evaluated the impact of human coronavirus infections on long-term neurodevelopmental domains including cognitive, language, academic, motor, and psychosocial outcomes. Conclusions Neurological manifestations of human coronavirus infections can cause severe disease in children. The case literature suggests a critical gap in knowledge of the long-term effects on child neurodevelopment of these infections. As the current SARS-CoV-2 pandemic continues, this gap must be filled to facilitate optimal outcomes in recovering children.

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Section: Discussionmentioning

confidence: 99%

Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance

Singer

Evankovich

Fisher

et al. 2021

Pediatric Neurology

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“…Their introduction through an NIHR programme grant in applied research was associated with a reduction in the time to aciclovir treatment for those with HSV encephalitis. The programme examined where delays occur, introduced innovative measures such as a lumbar puncture pack to streamline management [ 15 , 26 ], and included intense efforts to raise awareness of encephalitis and the national guidelines, in conjunction with The Encephalitis Society, our partner in patient and public involvement and engagement [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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

Defres,

Tharmaratnam,

Michael

et al. 2023

PLoS ONE

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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.

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“…A UK study showed that the median time to treatment for suspected HSV encephalitis was 48 (range: 2-432) hours (6). Since the publication of the clinical guidelines for the management of suspected encephalitis in 2012, more recent studies have shown a reduced median time to treatment for suspected encephalitis to around 15 hours (7, 8)). But while a number of studies have reported on the favourable (modified Rankin Scale of 0–3) clinical outcomes associated with the early treatment (≤ 48 hours from admission) of HSV encephalitis (9–15), there is limited research into the potential impact on healthcare resource utilisation and costs.…”

Section: Introductionmentioning

confidence: 99%

Health economic impact of early versus delayed treatment of herpes simplex virus encephalitis in the UK

Defres,

Navvuga,

Hardwick

et al. 2024

Preprint

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Objective: Thanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis health outcomes have improved. This paper evaluates the costs and the health-related quality of life implications of these guidelines. Design and setting: A sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015. Study participants: Data for patients aged ≥16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months. Primary and secondary outcome measures: Patient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS), and the EuroQoL; health care costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life years (QALYs) were calculated from the EQ-5D utility scores. Cost-utility analysis was performed using the NHS and Social Scare perspective. Results: A total of 49 patients were included, 35 treated within 48 hours ″early″ (median [IQR] 8.25 [3.7-20.5]) and 14 treated after 48 hours (median [IQR] 93.9 [66.7 - 100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0-3) compared to 4 (29%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p<0.000). After adjusting for age and symptom duration at admission, early treatment incurred a lower average cost at discharge, £23,086 (95% CI: £15,186 to £30,987) vs £42,405 (95% CI: £25,457 to £59,354) [p<0.04]. A -£20,218 (95% CI: -£52,173 to £11,783) cost difference was observed at 12-month follow-up post discharge. Conclusions: This study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment.

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

Cited by 6 publications

References 51 publications

Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance

Coronavirus Infections in the Nervous System of Children: A Scoping Review Making the Case for Long-Term Neurodevelopmental Surveillance

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

Health economic impact of early versus delayed treatment of herpes simplex virus encephalitis in the UK

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