Evolving etiologies, comorbidities, survival, and costs of care in adult encephalitis.

Encephalitis is a central nervous system disorder, often caused by infectious agents or aberrant immune responses. We investigated causes, comorbidities, costs, and outcomes of encephalitis in a population-based cohort. ICD-10 codes corresponding to encephalitis were used to identify health services records for all adults from 2004 to 2019. Data were cross-validated for identified diagnoses based on laboratory confirmation using univariate and multivariate statistical analyses. We identified persons with a diagnosis of encephalitis and abnormal cerebrospinal fluid (CSF) results (n = 581) in whom viral genome was detected (n = 315) in a population of 3.2 million adults from 2004 to 2019. Viral genome-positive CSF samples included HSV-1 (n = 133), VZV (n = 116), HSV-2 (n = 34), enterovirus (n = 4), EBV (n = 5), and CMV (n = 3) with the remaining viruses included JCV (n = 12) and HHV-6 (n = 1). The mean Charlson Comorbidity Index (2.0) and mortality rate (37.6%) were significantly higher in the CSF viral genome-negative encephalitis group although the mean costs of care were significantly higher for the CSF viral genome-positive group. Cumulative incidence rates showed increased CSF VZV detection in persons with encephalitis, which predominated in persons over 65 years with a higher mean Charlson index. We detected HSV-2 and VZV more frequently in CSF from encephalitis cases with greater material-social deprivation. The mean costs of care were significantly greater for HSV-1 encephalitis group. Encephalitis remains an important cause of neurological disability and death with a viral etiology in 54.2% of affected adults accompanied by substantial costs of care and mortality. Virus-associated encephalitis is evolving with increased VZV detection, especially in older persons.

The longitudinal health economic impact of viral encephalitis in the United States.

Introduction. Previous studies of viral encephalitis have focused on acute costs, estimating incidence at 7.3 per 100 000 and total US annual charges at $2 billion in 2010.Aim. We aim to quantify the most updated longitudinal health economic impact of viral encephalitis in the USA from 2008 to 2015.Methodology. Data on patients diagnosed with viral encephalitis were obtained from the Truven Health Analytics MarketScan database. Patients with a primary diagnosis of viral encephalitis, from herpetic viruses and other viral aetiologies (e.g. West Nile fever) were included in the analysis. Data concerning healthcare resource utilization, inpatient mortality, length of stay and accrued healthcare costs were collected for up to 5 years.Results. Among 3985 patients with continuous enrolment for 13 months prior to the encephalitis diagnosis, more non-herpes simplex encephalitis (61.7 %) than herpes simplex encephalitis (HSE; 38.3 %) cases were recorded, with the majority concentrated in the southern USA (29.2 %). One-year inpatient mortality was 6.2 %, which over a 5-year period rose to 8.9 % for HSE and 5.8 % for all other viral encephalitides. HSE resulted in longer cumulative stays in the hospital (11 days vs. 4 days; P=0.0025), and accrued 37 % higher first-year costs, after adjusting for known confounders [P<0.001, cost ratio=1.37, 95 % confidence interval (1.20, 1.57)]. Additionally, HSE was associated with greater 5-year cumulative median charges ($125 338 vs. $82 317, P=0.0015).Conclusion. The health economic impact and long-term morbidity of viral encephalitis in the USA are substantial.

Clinical manifestations of severe enterovirus 71 infection and early assessment in a Southern China population.

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.

The evaluation of a tailored intervention to improve the management of suspected viral encephalitis: protocol for a cluster randomised controlled trial.

BACKGROUND: Viral encephalitis is a devastating condition for which delayed treatment is associated with increased morbidity and mortality. Clinical audits indicate substantial scope for improved detection and treatment. Improvement strategies should ideally be tailored according to identified needs and barriers to change. The aim of the study is to evaluate the effectiveness and cost-effectiveness of a tailored intervention to improve the secondary care management of suspected encephalitis. METHODS/DESIGN: The study is a two-arm cluster randomised controlled trial with allocation by postgraduate deanery. Participants were identified from 24 hospitals nested within 12 postgraduate deaneries in the United Kingdom (UK). We developed a multifaceted intervention package including core and flexible components with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. The primary outcome will be a composite of the proportion of patients with suspected encephalitis receiving timely and appropriate diagnostic lumbar puncture within 12 h of hospital admission and aciclovir treatment within 6 h. We will gather outcome data pre-intervention and up to 12 months post-intervention from patient records. Statistical analysis at the cluster level will be blind to allocation. An economic evaluation will estimate intervention cost-effectiveness from the health service perspective. TRIAL REGISTRATION: Controlled Trials: ISRCTN06886935.

An assessment of the necessity of lumbar puncture in children with seizure and fever.

OBJECTIVE: It is frequently thought that lumbar puncture (LP), is a mandatory procedure in all children who have fever and a seizure; because a convulsion may be the sole clinical manifestations of bacterial meningitis. To assess whether meningitis could be recognized using readily available clinical information. METHODS: This study was done during a 4 yr period from 2002-2006. A total of 254 previously healthy children aged 6 months to 5 years, were brought consecutively to the paediatric department of a teaching university hospital after their first fever-associated-seizure; lumbar puncture (LP) was performed in all cases. Children with seizure and fever and meningitis served as cases and those with fever and seizure, but no meningitis, served as control. Factors compared in the two groups were: age, lethargy, irritability, vomiting, nuchal rigidity, bulging fontanel, headache, drowsiness, toxicity, coma, complex seizure, and prior antibiotic use. RESULTS: Twelve, (4.7%), cases were diagnosed as meningitis. Risk factors significantly associated with meningitis were: age < 12 months, lethargy, irritability, vomiting, nuchal rigidity, bulging fontanel, headache, drowsiness, toxicity, coma, complex seizure, and prior antibiotic use, (p < 0.05). All children with meningitis had at least one of the risk factors mentioned above. CONCLUSION: Our results indicate that based on available clinical data, meningitis can be ruled out in children presenting with seizure and fever; thus there is no need for routine lumbar puncture in all children who present with fever and seizure. However a lumbar puncture is mandatory in infants younger than 12 months or who have received prior antibiotics.

Use of the polymerase chain reaction in the diagnosis of herpes simplex encephalitis: a decision analysis model.

PURPOSE: To evaluate the utility of an assay based on a polymerase chain reaction (PCR) of cerebrospinal fluid in the management of patients with suspected herpes simplex encephalitis. METHODS: A decision model was constructed and used to compare a PCR-based approach with empiric therapy. Inputs required by the model included the sensitivity (96%) and specificity (99%) of PCR (derived from review of the literature), the prevalence of herpes simplex encephalitis (5%, based on the actual prevalence at Barnes Hospital among patients treated empirically with acyclovir), the outcomes for patients with and without herpes simplex encephalitis (derived from clinical studies of the Collaborative Antiviral Study Group and the actual experience at Barnes Hospital), and the average duration of empiric acyclovir therapy for patients with possible herpes simplex encephalitis (5.3 days based on actual experience at Barnes Hospital). RESULTS: Using these input values, the decision model predicted better outcomes with empiric therapy. However, low rates of inappropriate discontinuation of empiric therapy in patients with herpes simplex encephalitis or improved diagnosis and outcome resulting from a negative PCR assay result in patients without herpes simplex encephalitis led to better outcomes with the PCR-based approach. The PCR-based approach was associated with 9.2 fewer doses of acyclovir per patient. CONCLUSION: Based on the decision model using conservative assumptions, a PCR-based approach can yield better outcomes and reduced acyclovir use compared with empiric therapy.

Sensitivity analysis and the expected value of perfect information.

Measures of decision sensitivity that have been applied to medical decision problems were examined. Traditional threshold proximity methods have recently been supplemented by probabilistic sensitivity analysis, and by entropy-based measures of sensitivity. The authors propose a fourth measure based upon the expected value of perfect information (EVPI), which they believe superior both methodologically and pragmatically. Both the traditional and the newly suggested sensitivity measures focus entirely on the likelihood of decision change without attention to corresponding changes in payoff, which are often small. Consequently, these measures can dramatically overstate problem sensitivity. EVPI, on the other hand, incorporates both the probability of a decision change and the marginal benefit of such a change into a single measure, and therefore provides a superior picture of problem sensitivity. To lend support to this contention, the authors revisit three problems from the literature and compare the results of sensitivity analyses using probabilistic, entropy-based, and EVPI-based measures.

Herpes encephalitis in children. MRI assessment.

The magnetic resonance imaging (MRI) findings in 14 patients with biopsy or polymerase chain reaction proven herpes simplex encephalitis were retrospectively reviewed to evaluate the diagnostic value of MRI in the early diagnosis of herpes simplex encephalitis in children. In addition to the early findings, follow-up MRI scans were obtained in four patients. Typical limbic system involvement was seen in 78 percent of the cases. Contrast-enhanced MRI was found to be superior to routine MRI sequences and computerized tomography (CT) in the early detection of inflammation. Follow-up MR images in four patients demonstrated the volume loss and late petechial hemorrhage in the involved regions. Magnetic resonance imaging is the method of choice in the diagnosis and follow-up of herpes simplex encephalitis.

Acute herpes simplex encephalitis: clinical assessment and prognostic data.

Acute herpes simplex encephalitis (HSE) has a grave outcome, and detection of prognostic features is of clinical importance. Thirty patients with HSE were assessed in a retrospective study. Diagnosis was confirmed by serological methods using the indirect immunofluorescence technique (IFT). Antiviral treatment was given to 23 of the patients. Focal convulsions were more frequent in patients below 18 years of age, while confusion and memory disturbances were prevalent among patients above 18. The final outcome was influenced by the degree of severity of the disease at the peak and the state of consciousness and duration of disease prior to the initiation of anti-viral treatment. No correlation was found between antibody levels in serum or in CSF and the outcome. We conclude that the clinical degree of severity the duration of illness prior to treatment and state of consciousness at the initiation of anti-viral treatment are of prognostic importance.