Pediatric West Nile Virus-Associated Neuroinvasive Disease: A Review of the Literature.

Over the past two decades, West Nile virus has become the most common arbovirus in North America, leading to several outbreaks and infecting thousands of people. Mosquitos help transmit the virus in the majority of cases, but transmission occurs via blood transfusions, organ transplantation, and possibly pregnancy and breastfeeding. While most infected patients experience mild to no symptoms, thousands of West Nile virus-associated neuroinvasive cases have been reported in the United States, with over 700 cases occurring in children from 2003 to 2016. Neuroinvasive disease presents as meningitis, encephalitis, or acute flaccid paralysis, and carries a high likelihood of poor outcome, including severe neurological disability or death. To date, no pharmacologic treatment has proven effective. Therapeutic clinical trials have not been successfully completed due to the sporadic nature of viral outbreaks and resultant poor study enrollment. Although older age and chronic disease are risk factors for neuroinvasive West Nile virus disease in adults, the specific factors that influence the risk in pediatric populations have not been fully elucidated. This review summarizes the most recent literature regarding West Nile virus-associated neuroinvasive disease, especially as it pertains to the pediatric population. Moreover, the review describes the epidemiology, clinical, laboratory, and radiographic findings, and outlines the various therapies that have been trialed and potential future research directions.

Critical West Nile Neuroinvasive Disease.

BACKGROUND: Data to guide neurointensivists seeing patients with West Nile Neuroinvasive disease (WNND) are lacking. We present a comparatively large series of patients with WNND admitted to the intensive care unit (ICU) and provide data on their early diagnosis, triage to the ICU and predictors of short-term outcomes. METHODS: We retrospectively identified patients aged ≥ 18 years old with WNND from January 1999 to November 2016. Demographic and clinical data, the modified Rankin Scale at discharge and disposition were collected. Univariate analysis was performed to find predictors of ICU admission and to assess the impact of ICU admission on the short-term outcomes. P values < 0.05 were considered significant. RESULTS: Among 26 patients, 16 were admitted to the ICU. Age < 60 years and the presentation with encephalitis and acute flaccid paralysis predicted ICU admission (P = 0.044 and 0.0007). Among patients requiring ICU admission, four died and no one was discharged home. ICU admission predicted longer hospital stay (P = 0.021), inhospital death (P = 0.034), survival with inability to walk independently (P = 0.0094), and discharge disposition other than home (P = 0.007). In the ICU group, older age was associated with longer hospital stay (P = 0.0001) and inhospital death (P = 0.035). CONCLUSION: WNND requiring ICU care has a high morbidity and mortality, especially among older patients. Survivors are highly disabled at discharge, but many improve over time. Therefore, more data on the long-term prognosis of survivors are needed to guide the goals of care in the acute setting.

[Chronic post-dural headache secondary to meningitis].

In this case report a young man was admitted with fever and headache, and a lumbar puncture revealed viral meningitis. After discharge, the patient experienced persistent headache, which worsened, when he was in upright position. The condition was considered secondary to the meningitis. After 14 months, the patient was diagnosed with post-dural puncture headache and treated with an epidural blood patch (EBP). The patient experienced no headache for three months, whereafter it returned. Subsequent EBP's were unsuccessful. This case emphasizes the importance of paying attention to orthostatic components in headaches.

Severe Parechovirus 3 Infections in Young Infants-Kansas and Missouri, 2014.

BACKGROUND: Infection with parechovirus type 3 (PeV3) can cause severe neurologic and sepsis-like illness in young infants; clinical and epidemiologic descriptions have been limited. We aimed to characterize PeV3 illness and explore risk factors for acquisition in a cluster of neonatal cases at Children's Mercy Hospital in Kansas City, Missouri. METHODS: Cerebrospinal fluid specimens were obtained from infants aged <180 days who were hospitalized with sepsis-like illness or meningitis between June 1 and November 1, 2014. PeV-positive specimens were sequenced at the Centers for Disease Control and Prevention. We reviewed the medical and birth charts of the infants and performed face-to-face parent interviews. We analyzed characteristics according to infant age and intensive care admission status. RESULTS: We identified 35 cases of PeV infection in infants aged 5 to 56 days. Seven infants required intensive care (median age, 11 days vs 27 days among those who did not require intensive care; P = .0044). Six of these 7 infants had neurologic manifestations consistent with seizures, and all 6 of them were treated with acyclovir but subsequently tested negative for herpes simplex virus. Virus sequences formed 2 lineages, both of which were associated with severe illness. Half of the infants were reported to have household contacts who were ill during the week before onset. Infants aged ≤7 days at onset were more likely to have been delivered at the same hospital. CONCLUSIONS: PeV3 can cause severe neurologic illness in neonates, and younger infants are more likely to require intensive care. PeV3 should be considered along with herpes simplex virus and other pathogens when evaluating young infants with sepsis-like illness or meningitis. More widespread testing for PeV3 would enable us to gain a better understanding of the clinical scope and circulation of this virus.

Use of Testing for West Nile Virus and Other Arboviruses.

In the United States, the most commonly diagnosed arboviral disease is West Nile virus (WNV) infection. Diagnosis is made by detecting WNV IgG or viral genomic sequences in serum or cerebrospinal fluid. To determine frequency of this testing in WNV-endemic areas, we examined the proportion of tests ordered for patients with meningitis and encephalitis at 9 hospitals in Houston, Texas, USA. We identified 751 patients (567 adults, 184 children), among whom 390 (52%) experienced illness onset during WNV season (June-October). WNV testing was ordered for 281 (37%) of the 751; results indicated acute infection for 32 (11%). Characteristics associated with WNV testing were acute focal neurologic deficits; older age; magnetic resonance imaging; empirically prescribed antiviral therapy; worse clinical outcomes: and concomitant testing for mycobacterial, fungal, or other viral infections. Testing for WNV is underutilized, and testing of patients with more severe disease raises the possibility of diagnostic bias in epidemiologic studies.

Developmental outcomes in cerebrospinal fluid proven enteroviral meningitis in neonates > 32 weeks of gestation.

AIM: The aim of this study is to assess the short-term and long-term (1 year) outcomes of cerebrospinal fluid (CSF) confirmed enteroviral meningitis in neonates > 32 weeks of gestation. METHODS: A retrospective audit of neonates admitted between 1 July 2002 to 30 June 2012. RESULTS: Thirty-three neonates were diagnosed with enteroviral meningitis based on a positive CSF enteroviral PCR. Physical growth and neurodevelopmental outcomes at 1 year corrected for prematurity were available for 24 infants. All infants were alive at 1 year. The median weight, length and head circumference at 1 year were in the 72nd, 62nd and 78th centile and were comparable with the birth parameters. The mean general quotient (GQ) was 98.5 (SD 7.1) and was not significantly different from the population mean of 100.2 (P = 0.27). None of the infants had a GQ > 2SD below the population mean. Neurological recovery was complete in the 24 neonates assessed except one, who developed cerebral palsy, epilepsy and progressive hydrocephalus requiring ventriculoperitoneal shunt at 1 year. CONCLUSION: Neonatal enteroviral meningitis was associated with optimal growth and neurodevelopment in the majority of the infants at 1 year corrected for prematurity. Longer term studies are needed to better define developmental outcomes.

[Benign recurring aseptic meningitis. What requires our attention?]. / Benigne rekurrierende aseptische Meningitis. Worauf muss man achten?

Benign recurrent aseptic meningitis (BRAM) or Mollaret's meningitis is a rare disease characterized by recurrent episodes of aseptic meningitis followed by spontaneous recovery. Disease courses over several years have been reported. In most cases, BRAM is caused by HSV-2, less frequently by other viruses or autoimmune diseases. In up to 10 %, the aetiology remains unclear. We present a case of idiopathic BRAM and discuss clinical findings, diagnosis and therapeutic options of this rare illness.

[Management of suspected meningitis in the emergency department]. / Syndrome méningé fébrile au service des urgences : prise en charge.

Febrile meningeal syndrome is a medical emergency. Lumbar puncture keeps its gold-standard status as clinical findings are neither sensitive nor specific enough. Antibiotics and steroids are ideally administered within the first 30 minutes after admission when bacterial meningitis is suspected. A cerebral CT-scan before lumbar puncture is mandatory for selected patients only. PCR for viruses in the cerebrospinal fluid can inform diagnosis and treatment. Meningitis caused by enterovirus can usually be managed at home.

Le syndrome méningé fébrile est une urgence majeure. La clinique n'étant pas suffisamment sensible ni spécifique, la ponction lombaire reste l'examen de choix pour établir le diagnostic. Lors de suspicion de méningite bactérienne, l'antibiothérapie associée à des stéroïdes doit être administrée dans les 30 minutes après l'admission. L'imagerie cérébrale n'est réalisée avant la ponction lombaire que dans des situations bien définies. Lors de méningite virale, la réalisation de PCR (polymerase chain reaction) dans le liquide céphalorachidien permet d'orienter le diagnostic et le traitement. Lorsqu'un entérovirus est identifié, la prise en charge peut habituellement se faire en ambulatoire.

Meningitis in service-age personnel.

The incidence of meningitis is declining in the UK population largely due to increased availability of vaccinations against the most common bacterial strains. Acute bacterial meningitis, however, is a life-threatening condition and distinguishing it from more benign causes of headache and fever is difficult in an operational environment due to limited access to diagnostic tests. Despite medical advances, the case fatality rate in the United Kingdom in adults with invasive meningococcal disease is 10.5%. Acute bacterial meningitis presents with the classical triad of fever, neck pain and altered mental state in less than half of adults, and in the initial course of the disease it frequently mimics common viral illnesses. The aim of this article is to discuss the recognition and management of meningitis with special emphasis on the deployed military environment.

Clinical, neuropathological and radiological evidence for a rare complication of rituximab therapy.

We report a rare case of myofasciitis and meningitis with deafness caused by systemic enterovirus infection in the setting of hypogammaglobulinaemia induced by rituximab. Whilst effective and generally safe, anti- CD 20 antibody therapy is increasingly recognised to result in unusual infectious complications to be considered in a treated patient presenting with neurological symptoms. These cases may pose diagnostic difficulties and can have atypical presentations. We present this rare complication of rituximab therapy, with histopathological confirmation of myofasciitis. In the older literature, enterovirus associated myofasciitis may have erroneously been termed dermatomyositis and we review the literature to demonstrate this important nosological point.

Parâmetros laboratoriais do líquido cefalorraquidiano em indivíduos com meningite por enterovírus / Laboratory parameters of cerebrospinal fluid in individuals with enterovirus meningitis

A meningite é a principal síndrome infecciosa que afeta o sistema nervoso central, e grande parte dos casos são ocasionados por infecções virais, principalmente por Enterovirus. O diagnóstico clínico para a verificação da etiologia da meningite ainda apresenta grandes desafios. O teste de Reação em Cadeia da Polimerase, leucócitos, hemácias, glicose, proteína e lactato no líquido cefalorraquidiano fornecem os primeiros indícios para o diagnóstico. No entanto, os valores de referência de alguns parâmetros podem sofrer alteraçõesOBJETIVO: Verificar parâmetros laboratoriais do líquido cefalorraquidiano em indivíduos com meningite por Enterovirus e, posteriormente, analisar suas relações por faixa etáriaMÉTODO: Foi realizado um estudo descritivo, com base nos dados do serviço de referência de coleta de líquido cefalorraquiano, localizado em São Paulo, Brasil. Totalizou-se em 202 indivíduos que apresentaram meningite por Enterovirus. Os dados foram analisados pelo teste de Shapiro-Wilk e Kruskal-Wallis (IC = 95%, p < 0,05) e representados pela mediana e percentil 25 e 75...

Meningitis is the leading infectious syndrome that affects the central nervous system, and most cases are caused by viral infections, mainly enterovirus. The clinical diagnosis for meningitis etiology still presents major challenges. The analysis of polymerase chain reaction (PCR), white blood cells, red blood cells, glucose, protein, and lactate in the cerebrospinal fluid (CSF) provides the first clues to the diagnosis. However, the reference values of some parameters can suffer changesOBJECTIVE: Analyze the laboratory parameters of CSF in patients with enterovirus meningitis, and then, theirrelationship by age groupMETHODS: A descriptive study was conducted based on data from a CSF reference service, located in São Paulo, Brazil, on 202 individuals who had enterovirus meningitis. Data was analysed by the Shapiro-Wilk and Kruskal-Wallis tests (CI = 95%, p < 0.05) and represented by the median and percentile 25 and 75, respectively...

Update on the diagnosis and management of tuberculous meningitis in children.

Tuberculous meningitis (TBM), the most devastating manifestation of tuberculosis, is often missed or overlooked because of nonspecific symptoms and difficulties in diagnosis. It continues to be an important cause of neurologic handicap in resource-poor countries. Owing to the suboptimal performance of diagnostic tests of TBM, diagnosis relies on thorough history, clinical examination, and relevant investigations. The development of affordable, accurate diagnostic tests for TBM in resource-poor settings remains a priority. Short intensified treatment is safe and effective in both human immunodeficiency virus (HIV)-infected and HIV-uninfected children. Treatment of tuberculous hydrocephalus depends on the level of the cerebrospinal fluid obstruction. Corticosteroids reduce risk of neurodisability and death in HIV-uninfected children. Thalidomide should be considered in children compromised by tuberculosis abscesses and tuberculous-related optochiasmic arachnoiditis. In resource-poor countries, home-based TBM treatment after initial in-hospital stabilization is feasible in carefully selected patients. Early diagnosis and treatment of TBM is the single most important factor determining outcome.

Viral meningitis admitted to an infectious diseases hospital: a retrospective case series.

UNLABELLED: Given its epidemic potential and development of severe forms of disease, viral meningitis (VM) is a serious public health problem. AIM: to characterize the main clinical, epidemiologic features, the etiology and treatment of VM cases admitted to the Iasi Infectious Diseases Hospital, in 2012. MATERIAL AND METHODS: We retrospectively analyzed the medical records of the patients admitted for viral meningitis at the Iasi "St. Parascheva" Infectious Diseases Hospital in the interval January 1- December 31, 2012 (98 cases). The etiologic diagnosis was made by determining the IgM/IgG antibodies against Coxsackie virus and/or West Nile virus in blood/CSF. RESULTS: There was a fourfold increase in the number of cases as compared to the average for the years 2009-2011. Most cases (73.5%) were children aged 1 to 14 years. 61.8% of patients were males, 51.7% from urban areas. The most common symptom was headache (85.7%), followed by fever (77.6%), and vomiting (66.3%). Neck stiffness was absent in 28.6% cases. In43.5% of the 39 patients serologically investigated a Coxsackie virus infection was confirmed and 1/20 was positive for West Nile virus; three varicella-zoster virus infections and one mumps infection were diagnosed clinically. 68.3% of the patients received first-line antibiotic treatment. CONCLUSIONS: The illness mainly affected children, fever and neck stiffness being sometimes absent. The etiology was known in 22.4% of cases; enter viruses being the most frequent causative agent. Most patients received antibiotic therapy. The course was favorable in all cases.

Viral meningitis and encephalitis.

Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date.

Trends in the management of viral meningitis at United States children's hospitals.

OBJECTIVE: To determine trends in the diagnosis and management of children with viral meningitis at US children's hospitals. METHODS: We performed a multicenter cross sectional study of children presenting to the emergency department (ED) across the 41 pediatric tertiary-care hospitals participating in the Pediatric Health Information System between January 1, 2005, and December 31, 2011. A case of viral meningitis was defined by International Classification of Diseases, Ninth Revision, discharge diagnosis, and required performance of a lumbar puncture. We examined trends in diagnosis, antibiotic use, and resource utilization for children with viral meningitis over the study period. RESULTS: We identified 7618 children with viral meningitis (0.05% of ED visits during the study period). Fifty-two percent of patients were <1 year of age, and 43% were female. The absolute number and the proportion of ED visits for children with viral meningitis declined from 0.98 cases per 1000 ED visits in 2005 to 0.25 cases in 2011 (P < .001). Most children with viral meningitis received a parenteral antibiotic (85%), and were hospitalized (91%). Overall costs for children for children with viral meningitis remain substantial (median cost per case $5056, interquartile range $3572-$7141). CONCLUSIONS: Between 2005 and 2011, viral meningitis diagnoses at US children's hospitals declined. However, most of these children are hospitalized, and the cost for caring for these children remains considerable.

Viral meningitis: which patients can be discharged from the emergency department?

BACKGROUND: Even in an era when cases of viral meningitis outnumber bacterial meningitis by at least 25:1, most patients with clinical meningitis are hospitalized. OBJECTIVE: We describe the clinical characteristics of an unusual outbreak of viral meningitis that featured markedly elevated cerebrospinal fluid white blood cell counts (CSF WBC). A validated prediction model for viral meningitis was applied to determine which hospital admissions could have been avoided. METHODS: Data were collected retrospectively from patients presenting to our tertiary care center. Charts were reviewed in patients with CSF pleocytosis (CSF WBC > 7 cells/mm(3)) and a clinical diagnosis of meningitis between March 1, 2003 and July 1, 2003. Cases were identified through hospital infection control and by surveying all CSF specimens submitted to the microbiology laboratory during the outbreak. RESULTS: There were 78 cases of viral meningitis and 1 case of bacterial meningitis identified. Fifty-eight percent of the viral meningitis cases were confirmed by culture or polymerase chain reaction to be due to Enterovirus. Mean CSF WBC count was 571 cells/mm(3), including 20 patients with a CSF WBC count > 750 cells/mm(3) (25%) and 11 patients with values > 1000 cells/mm(3) (14%). Sixty-four of 78 patients (82%) were hospitalized. Rates of headache, photophobia, nuchal rigidity, vomiting, and administration of intravenous fluids in the Emergency Department were no different between admitted and discharged patients. Only 26/78 (33%) patients with viral meningitis would have been admitted if the prediction model had been used. CONCLUSIONS: Although not all cases of viral meningitis are necessarily suitable for outpatient management, use of a prediction model for viral meningitis may have helped decrease hospitalization by nearly 60%, even though this outbreak was characterized by unusually high levels of CSF pleocytosis.

Impact of polymerase chain reaction results on patient management during a viral meningitis outbreak in Tropical North Queensland.

OBJECTIVES: Enterovirus is the most commonly isolated pathogen in viral meningitis. We report on the first outbreak of viral meningitis in Tropical Queensland and the effect of polymerase chain reaction (PCR) results on antibiotic use and hospital length of stay. METHODS: Retrospective case series of consecutive patients presenting to the Townsville ED with viral meningitis were evaluated by examining hospital medical records. The study period was November 2008 to February 2009. RESULTS: Forty-three patients were available for full analysis of which 17 (40%) were female and 17 (40%) had a positive enteroviral PCR. Antibiotics were commenced on 37 (86%) of patients. There was no difference in hospital length of stay in patients with a negative versus positive PCR (2.52 vs 2.72 days, P = 0.68) or duration of antibiotic therapy (2.20 vs 1.94 days, P = 0.61). CONCLUSION: In our study a positive result on PCR was not associated with a shorter hospital length of stay or a shorter duration of antibiotic therapy. This contrasts with previous reports on this topic and requires further evaluation.