Viral Meningitis Research Articles

Frequency of Meningitis Among Infants and Young Children With Clinically Diagnosed First Time Febrile Seizure

Background: Patients with bacterial meningitis (BM) frequently present with febrile seizures (FS) without any signs or symptoms of BM. To perform a lumbar puncture on all FS patients to rule out meningitis is still debatable. The goal of this study was to estimate the frequency of meningitis among first-time febrile seizures (FTFS). Methods: From July 2013 to June 2014, a cross-sectional study was conducted at Sir Salimullah Medical College and Mitford Hospital, Dhaka. CSF and blood reports and detailed histories and examinations were examined in children aged 6 months to 36 months with FTFS (simple or complex). Results: The first complex febrile seizure (FCFS) and the first simple febrile seizure (FSFS) occurred in 58% and 42% of the 73 children included in this study. 11 (15%) cases had meningitis based on CSF and blood reports, where 2 (3%) had confirmed BM, 2 (3%) had probable BM, and 7 (10%) had viral meningitis (PVM). One of two children with confirmed BM had Klebsiella spp. in CSF culture and Streptococcus pneumoniae in CSF gram stain. Others with probable BM had CSF pleocytosis with low sugar and high protein levels. Leukocytosis was found in all four children with BM. Two of the seven children with PVM had isolated pleocytosis, one had low sugar, and four had high protein CSF. Blood cultures were negative in all 11 meningitis cases. Conclusion: Although meningitis is common in FCFS, this study found no cases of BM children with FSFS, though PVM was not uncommon. Sir Salimullah Med Coll J 2022; 30: 108-114

Review on Viral Encephalitis-

Background: Inflammation of the brain parenchyma brought on by a virus is known as viral encephalitis. It coexists frequently with viral meningitis and is the most prevalent kind of encephalitis. Objectives: To throw light on viral encephalitis, its types, epidemiology, symptoms and complications. Results: Although it can affect people of all ages, viral infections are the most prevalent cause of viral encephalitis, which is typically seen in young children and old people. Arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumoviruses, and coronaviruses are just a few of the viruses that have been known to cause encephalitis. Conclusion: As new viruses emerge, diagnostic techniques advance, or we learn more about the pathophysiology of the disease, viral encephalitis has become a more serious public health concern.

Epidemiology and Disease Burden of Hospitalized Children With Viral Central Nervous System Infections in China, 2016 to 2020

BackgroundViral central nervous system (CNS) infections seriously threaten the life and health of children, with a high mortality and severe sequelae in China and globally. Surveillance of viral CNS infections in children is important, especially in hospitalized children, to facilitate disease evaluation. MethodsIn this study, we collected the data on the discharged Face Sheet of Medical Records from database from 2016 to 2020 and analyzed the epidemiologic characteristics and disease burden of hospitalized children (≤18 years old) with viral CNS infections in China. We classified the discharge diagnosis of viral CNS infection as viral encephalitis (VE), viral meningitis (VM), viral meningoencephalitis (VME), viral encephalomyelitis (VEM), and viral meningomyelitis (VMM). ResultsA total of 42,641 cases of viral CNS infections were included in the database, consisting of 39,279 cases with VE (92.47%), 2011 cases with VM (4.73%), 1189 cases with VME (2.80%), 118 cases with VEM (0.28%), and 44 cases with VMM (0.10%). The number of hospitalized patients with viral CNS infections accounted for 0.74% (42,641 of 5,790,910) of all hospitalized cases. The onset of viral CNS infections presented seasonal characteristic, with peaks in June to July and December to January. Seizures are the most frequent complication of this disorder. Median length of stay and inpatient expenditures for patients with viral CNS infections were 9 days and 1144.36 USD. Causative viruses were identified in 4.33% (1848 of 42,641) of patients. ConclusionsThis study will help understand the clinical epidemiology and disease burden of hospitalized children with viral CNS infections in China.

A risk score for identifying patients at a low risk of bacterial meningitis amongst adults with cerebrospinal fluid leucocytosis and a negative gram stain result: a derivation and validation study

ObjectivesWe aimed to derive and validate a risk score to differentiate patients with bacterial meningitis from those with viral meningitis or encephalitis amongst patients presenting with cerebrospinal fluid (CSF) leucocytosis and a negative Gram staining result. MethodsWe included adults with bacterial and viral meningitis or encephalitis presenting with CSF leukocyte counts of >10 per mm3 and a negative Gram staining result from cohorts in Houston, Texas (2004–2019), and the Netherlands (2012–2021). Derivation and the first validation were performed in the American patients and further validation in the Dutch patients. ResultsDerivation was performed in 109 American patients with bacterial meningitis (median age, 56 years; interquartile range [IQR], 46–66 years; 46% women) and 194 with viral meningitis or encephalitis (median age, 46 years; IQR, 33–60 years; 53% women). Serum leukocyte counts of >10.0 × 109/L, CSF leukocyte counts of >2000 per mm3, granulocyte counts of >1180 per mm3, protein levels of >2.2 g/L, glucose levels of <1.9 mmol/L and fever on admission were included in the risk score, which was dichotomized into ‘low risk’ (0 present) and ‘high risk’ (>0 present). The first validation showed a sensitivity of 100% (95% CI, 96.6–100) and specificity of 34.0% (95% CI, 27.4–41.2). Further validation in 262 Dutch patients with bacterial meningitis (median age, 57 years; IQR 44–70 years; 45% women) and 68 with viral meningitis (median age, 34 years; IQR, 28–45 years; 60% women) showed a sensitivity of 99.6% (95% CI, 97.9–100) and specificity of 41.2% (95% CI, 29.4–53.7). ConclusionsOur risk score may be able to rule out bacterial meningitis amongst patients presenting with CSF leucocytosis and a negative Gram staining result. However, it needs prospective testing prior to clinical implementation.

A Little Neutrophil Predominance May Not Be a Harbinger of Death: Clinical and Laboratory Characteristics of Meningitis in Jordan.

Background This study aims to evaluate the clinical features, laboratory findings, and outcomes of children and adults diagnosed with meningitis in Jordan. Methodology This is a retrospective chart review study that targeted patients diagnosed with meningitis at King Abdullah University Hospital, a tertiary care center in Northern Jordan, from March 21, 2015, to March 31, 2019. Patients were included in this study if they were older than 28 days and had no risk factors for meningitis. Results A total of 169 patients met the inclusion criteria. Males were overrepresented (67%) and were significantly younger than females (6 vs. 17 years, p = 0.01). Positive meningeal signs were not predictive of greater cerebrospinal fluid leukocytosis (p = 0.348), and they did not provide sufficient sensitivity to be used as screening tools. The most common etiology was aseptic (49%), followed by enterovirus (43%), while bacterial meningitis was an uncommon diagnosis (3.5%). Nearly half of the patients took antibiotics prior to their hospital presentation. During in-hospital admission, six patients died, four of whom had bacterial and two had aseptic meningitis. Enteroviral meningitis showed neutrophil predominance in 44% of cases on lumbar puncture and had a higher neutrophil proportion compared to aseptic meningitis (p = 0.026). Streptococcus pneumoniae was the most common bacterial etiology identified. Conclusions Meningitis in Jordan is most commonly of aseptic and enteroviral origin, and these etiologies carry significantly more favorable outcomes compared to bacterial meningitis. Enteroviral meningitis displays a higher percentage of neutrophils in cerebrospinal fluid compared to aseptic meningitis. S. pneumoniae is the leading cause of bacterial meningitis.Slight neutrophil predominance above halfis a weak predictor of bacterial meningitis due to the small contribution of bacteria asa cause among enteroviruses and aseptic etiologies.

The introduction of mutations in the wild type coxsackievirus B3 (CVB3) IRES RNA leads to different levels of in vitro reduced replicative and translation efficiencies.

Coxsackievirus B3 (CVB3) is a principal causative agent of viral myocarditis, meningitis and pancreatitis. There is no vaccine available for clinical use. It has been demonstrated that the primary molecular determinant of virulence phenotype is located in the 5’ UTR of the viral genome. Translation initiation of CVB3 RNA is directed by the IRES element situated in the 5’UTR. In the present study, we analyse the effects of single point mutations introduced in different positions in the domain V of the IRES RNA of CVB3 wild type. We characterize in vitro virus replicative capacitiy and translation efficiency and we test in vivo virulence of different CVB3 mutants produced by the introduction of different mutations in the domain V of IRES by site-directed mutagenesis to abolish its structure. Our results demonstrate that all RNA mutants display different levels of decreased replication and translation initiation efficiency in vitro. The translation defect was correlated with significant reduced viral titer of mutant particles in comparison with the wild type. When inoculated in mice, mutant viruses were checked for inflammation and necrosis.In vitro and in vivo Findings strongly suggest that the most attenuated mutant strain could be considered a candidate for live-attenuated CVB3 vaccine.

RESULTS OF MONITORING THE INCIDENCE OF NON-POLIO ENTEROVIRUS INFECTION IN THE PRE-PANDEMIC AND PANDEMIC PERIODS

The results of monitoring the incidence of non-polio enterovirus infection (EVI) in the pre-pandemic and pandemic periods in the Khanty-Mansiysk Autonomous Okrug (2006-2021) are presented. It was found that the predominant share in the total incidence of EVI was urban population with a predominance of children under 6 years of age and school age. In the period 2020-2021. The low incidence of EVI was due to ongoing anti-epidemic measures against COVID-19 and was accompanied by the spread of enterovirus serotype CVA6, which is able to effectively implement the aspiration mechanism of transmission of the infectious agent and cause respiratory and exanthemic diseases. The spread of CVA6 was influenced by the growth of migration activity of the population, due to the partial lifting of restrictions and an increase in the non-immune stratum of the population due to a decrease in the incidence of EVI in 2020. The results of the study will contribute to the adoption of measures leading to a decrease in the incidence of EVI in the Khanty-Mansiysk Autonomous Okrug, rational planning of preventive measures, by improving the information and diagnostic subsystems of epidemiological surveillance. To solve these tasks, it is necessary to further study the spectrum of enteroviruses circulating on the territory of the Khanty-Mansi Autonomous Okrug, the frequency of their occurrence in subclinical forms of EVI and as etiological agents of enterovirus meningitis, the development of molecular genetic typing techniques using mass parallel high-performance sequencing technology, the study of molecular genetic characteristics. All this will reduce the risks of EVI morbidity in the post-pandemic period and ensure the sanitary and epidemiological well-being of the population and prevent the spread of EVI in the Khanty-Mansi Autonomous Okrug.

Arbovirus fevers in children and adults in the Astrakhan region: clinical cases

Natural focal infections with transmissible transmission caused by viruses of West Nile Fever, Batai, Inco, Sindbis, Tyagin are registered in various territories of Russia, in the form of sporadic cases, characterized by polymorphism of clinical symptoms, from inapparent forms to severe, occurring with Central nervous system damage (meningitis, meningoencephalitis), which complicates the timely diagnosis and treatment of this pathology.Purpose: to describe our own clinical observations of five cases of arbovirus fevers.Results. Arbovirus fevers (West Nile Fever, Batai, Inko, Tyaginya) in the five clinical cases we have presented occurred in two clinical forms: catarrhal with hypertension syndrome, febrile fever and intense headache, vomiting in the absence of signs of inflammation in the CSF; and with damage to the central nervous system (meningitis). Catarrhal forms of arboviral fevers must be differentiated from ARVI, influenza, mononucleosis. Arbovirus fevers occurring with Central nervous system lesions (meningitis) had a significant similarity with enteroviral meningitis, both in terms of seasonality and clinical symptoms.Conclusion. In the territories of Russia endemic for mosquito fevers, in the summer period of the year, febrile patients with cerebral symptoms and / or meningeal symptoms should be examined for a group of arbovirus fevers.

Enterovirus 3C Protease Cleaves TRIM7 To Dampen Its Antiviral Activity.

Mammalian TRIM7 is an antiviral protein that inhibits multiple human enteroviruses by degrading the viral 2BC protein. Whether TRIM7 is reciprocally targeted by enteroviruses is not known. Here, we report that the 3C protease (3Cpro) from two enteroviruses, coxsackievirus B3 (CVB3) and poliovirus, targets TRIM7 for cleavage. CVB3 3Cpro cleaves TRIM7 at glutamine 24 (Q24), resulting in a truncated TRIM7 that fails to inhibit CVB3 due to dampened E3 ubiquitin ligase activity. TRIM7 Q24 is highly conserved across mammals, except in marsupials, which instead have a naturally occurring histidine (H24) that is not subject to 3Cpro cleavage. Marsupials also express two isoforms of TRIM7, and the two proteins from koalas have distinct antiviral activities. The longer isoform contains an additional exon due to alternate splice site usage. This additional exon contains a unique 3Cpro cleavage site, suggesting that certain enteroviruses may have evolved to target marsupial TRIM7 even if the canonical Q24 is missing. Combined with computational analyses indicating that TRIM7 is rapidly evolving, our data raise the possibility that TRIM7 may be targeted by enterovirus evasion strategies and that evolution of TRIM7 across mammals may have conferred unique antiviral properties. IMPORTANCE Enteroviruses are significant human pathogens that cause viral myocarditis, pancreatitis, and meningitis. Knowing how the host controls these viruses and how the viruses may evade host restriction is important for understanding fundamental concepts in antiviral immunity and for informing potential therapeutic interventions. In this study, we demonstrate that coxsackievirus B3 uses its virally encoded protease to target the host antiviral protein TRIM7 for cleavage, suggesting a potential mechanism of viral immune evasion. We additionally show that TRIM7 has evolved in certain mammalian lineages to express protein variants with distinct antiviral activities and susceptibilities to viral protease-mediated cleavage.

West Nile Disease Symptoms and Comorbidities: A Systematic Review and Analysis of Cases.

West Nile virus (WNV) is a mosquito-borne flavivirus that has emerged as a major cause of viral encephalitis and meningitis, rarely leading to death. Several risk factors have been discussed in the past concerning the severity of the disease, while few reports have focused on precipitating conditions that determine of WNV-related death. Studies on cohorts of patients suffering of West Nile disease (WND) usually encompass low numbers of deceased patients as a result of the rarity of the event. In this systematic review and critical analysis of 428 published case studies and case series, we sought to evaluate and highlight critical parameters of WND-related death. We summarized the symptoms, comorbidities, and treatment strategies related to WND in all published cases of patients that included clinical features. Symptoms such as altered mental status and renal problems presented increased incidence among deceased patients, while these patients presented increased cerebrospinal fluid (CSF) glucose. Our analysis also highlights underestimated comorbidities such as pulmonary disease to act as precipitating conditions in WND, as they were significantly increased amongst deceased patients. CSF glucose and the role of pulmonary diseases need to be revaluated either retrospectively or prospectively in WND patient cohorts, as they may be linked to increased mortality risk.

Viral Infection

Viral central nervous system(CNS)infections due to direct viral infection in the CNS include encephalitis/myelitis and meningitis. Acute encephalopathy is a CNS disorder that is mainly associated with viral respiratory infections. This article outlines herpes encephalitis, poliomyelitis, enterovirus A71 brainstem encephalitis/myelitis, and enterovirus D68 paralytic myelitis as acute encephalitis/myelitis, enteroviral meningitis and mumps meningitis as acute viral meningitis, and influenza encephalopathy and HHV-6 encephalopathy as acute encephalopathy.

Diagnostic Accuracy of MRI for Detection of Meningitis in Infants.

To determine the accuracy of MR imaging for diagnosis of meningitis in infants. Retrospective review of infants less than 1 year of age who underwent a brain MR imaging for meningitis from 2010-2018. Gold standard for diagnosis of bacterial meningitis was a positive bacterial CSF culture or a positive blood culture with an elevated CSF WBC count, and diagnosis of viral meningitis was a positive CSF PCR result and elevated CSF WBC count. Sensitivity, specificity, PPV, NPV, and accuracy for MR imaging diagnosis of meningitis were calculated. Two hundred nine infants with mean age 80 days (range 0-347 days) were included. There were 178 true positives with the most common pathogens being: Group B Streptococcus (58), E. coli (50), Streptococcus pneumoniae (21), H. influenzae (4); Herpes simplex virus 1 or 2 (18); Enterovirus (4); and other (23). There were 31 true negatives. Range of sensitivity, specificity, PPV, NPV, and accuracy of MR imaging for detection of meningitis was 67.4-83.5%, 92.3-95.7%, 95.0-98.6%, 33.3-76.5%, and 71.3-86.5% respectively. MR imaging sensitivity decreased after 10 days from time of presentation while specificity remained stable. Among individual MR imaging findings, leptomeningeal enhancement was the most sensitive finding, while cerebritis, infarction, ventriculitis, abscess, and intraventricular purulent material were the most specific findings. MR imaging of the brain demonstrates high specificity and moderate sensitivity for diagnosis among infants presenting with signs and symptoms of meningitis. The results reflect current standard of care for imaging of infants with meningitis however a selection bias for imaging of more severe meningitis may affect these results.

Interpretation of white blood cell counts in the cerebrospinal fluid of neonates with traumatic lumbar puncture: a retrospective cohort study

BackgroundDifficulty in interpreting white blood cell (WBC) counts in cerebrospinal fluid (CSF) complicates the diagnosis of neonatal meningitis in traumatic lumbar punctures (LP). The aim of our study was to determine the correction factor for WBC counts in traumatic LP that offers the greatest diagnostic efficacy in meningitis.MethodsWe conducted a retrospective observational study of LP in neonates between January 2014 and December 2020. Traumatic LP was defined as a red blood cell (RBC) count ≥ 1,000 cells/mm3 CSF and pleocytosis as WBCs ≥ 20 cells/mm3 CSF. The CSF RBC:WBC ratio was analyzed by linear regression to determine a new correction factor. Cell count adjustments were also studied using the 500:1, the 1,000:1 ratio method, and the peripheral blood RBC:WBC ratio, using ROC curves and studies of accuracy (sensitivity and specificity).ResultsOverall, 41.0% of the 1,053 LPs included in the study were traumatic. The best results for effective WBC correction were the method based on the peripheral blood ratio (sensitivity = 1.0 and specificity = 0.9 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.9 for viral meningitis) and the 400:1 ratio (sensitivity = 1.0 and specificity = 0.8 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.8 for viral meningitis) obtained from linear regression (95% CI 381.7–427.4; R2 = 0.7).ConclusionBoth the peripheral blood correction and the 400:1 correction reduce the number of neonates classified with pleocytosis who were not eventually diagnosed with meningitis. Both methods might be a useful tool to clarify the neonatal meningitis diagnosis, offering neonatologists the possibility to assess the WBC count in traumatic LP.

Heparin Binding Protein in Early Differential Diagnosis of Bacterial Meningitis.

Heparin-binding protein is a serine protease that is mobilized rapidly from emigrating polymorphonuclear leukocytes that acts as a chemoattractant activator of monocyte and macrophages. We investigated the potential role and efficacy of serum and cerebrospinal fluid heparin binding protein in differentiating bacterial meningitis from tuberculosis and viral meningitis. A case diagnosed with acute bacterial meningitis (n:37), viral meningitis (n:30) and tuberculous meningitis (n:30) was included in this study. The diagnosis was based on history, clinical criteria, cerebrospinal fluid examination, latex agglutination and culture, and response to therapy. Heparin-binding protein was measured using enzyme-linked immunosorbent technique in both cerebrospinal fluid and serum. Cerebrospinal fluid heparin-binding protein levels were 7.81 ± 0.23ng/mL in bacterial meningitis, 6.11 ± 0.3ng/mL in tuberculosis meningitis and 5.75 ± 0.1ng/mL in viral meningitis. The mean serum level was 14.98 ± 1.1ng/mL in bacterial meningitis, 6.89 ± 0.4ng/mL in tuberculosis meningitis, and 6.02 ± 0.4ng/mL in viral meningitis. Both heparin-binding protein levels were significantly higher in patients with bacterial meningitis. We found that serum and cerebrospinal fluid heparin binding protein is a useful marker for differentiating bacterial meningitis from non-bacterial meningitis.

A hidden infection: Racemose neurocysticercosis causing hydrocephalus; a case report

Introduction and importanceNeurocysticercosis (NCC) is the most common helminthic central nervous system infection (CNS) in the Western hemisphere and the most common cause of acquired epilepsy worldwide. Due to its relatively prolonged latent period and clinical similarity to other infectious diseases – including bacterial or viral meningitis and other helminthic infections – NCC may be difficult to diagnose, especially for clinicians who rarely encounter it.Case presentationThis case report discusses a patient with obstructive hydrocephalus and eosinophilic meningitis secondary to racemose NCC. The diagnosis process was initially complicated by the patient's history of pork allergy and absence of radiographic evidence of helminthic CNS infection. Further investigation showed a 4th ventricle multi-cystic lesion causing hydrocephalus which prompted a surgical intervention with a ventriculoperitoneal shunt (VPS) in conjunction with anti-helminthic medical treatment. At 1-year follow-up, the patient has reported recurrence of VPS related complications.Clinical discussionLarval cysts typically deposit within the brain parenchyma, making them easily detected on head computed tomography (CT) scans and leading to neurologic sequelae such as epilepsy. In this case, the absence of CT evidence of NCC and the patient's lifelong history of pork allergy slowed the diagnosis process.ConclusionRacemose NCC is a rare subset of the disease in which cyst clusters occupy the extra parenchymal space, thereby changing the symptomatic profile and making the cysts more difficult to visualize in imaging studies. In this case, magnetic resonance imaging (MRI) was the best imaging modality to diagnosis extra parenchymal NCC and guide its surgical management.

Serotype analysis of pediatric enteroviral meningitis in Gwangju, Republic of Korea: Number of annual cases, distribution by age group, and characteristics of each serotype.

Enteroviral meningitis is a common disease in children; however, serotype data are still lacking, especially for late childhood. This study analyzed the number of annual cases, distribution by age group, and characteristics of each serotype among children with enteroviral meningitis. After the initial screening of 1,009 children (<18 years) with viral meningitis between 2008 and 2021, the data of enteroviral meningitis were retrospectively reviewed. The number of annual cases and serotypes were investigated. The distribution of serotypes across different ages was reviewed. Clinical characteristics of the major serotypes (detected in at least 15 patients) were further examined. Among the 700 patients with enteroviral meningitis, serotypes were tested in 517 patients (73.9%), which could be typed in 370 patients (71.6%). EV-A71 was the most common serotype detected in 2010, 2012, and 2019. After 2020, enterovirus was rarely detected. The group B coxsackieviruses (CVBs) were commonly detected in neonates (CVB1, 33.3%) and infants (CVB5, 17.4%). The echoviruses were commonly detected beyond infancy; E30 was the most frequently detected in late childhood (14.4%) and adolescents (15.4%). EV-A71 was the most frequently detected in early childhood (17.2%). Between the 11 major serotypes, vomiting, headache, and irritability were more commonly associated with echoviruses (P <0.01). In EV-A71, neurologic symptoms and skin lesions were more common (P <0.01). The CVBs were commonly detected in neonates and infants, whereas the echoviruses were commonly detected beyond infancy and caused vomiting, headache, and irritability. EV-A71 was the most frequently detected in early childhood, frequently causing neurologic and dermatologic problems.

Efficacy and safety of GSP301 nasal spray in children aged 6 to 11 years with seasonal allergic rhinitis

BackgroundGSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate. ObjectiveTo evaluate the efficacy, safety, and tolerability of GSP301 in pediatric patients (aged ≥6 to <12 years) with seasonal allergic rhinitis (SAR). MethodsThis double-blind, randomized, parallel-group study randomized 446 eligible patients 1:1 (GSP301 [olopatadine hydrochloride 665 μg and mometasone furoate 25 μg] or placebo) as 1 spray/each nostril twice daily for 14 days. The primary end point was change from baseline in average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over a 14-day treatment period analyzed using mixed-effect model repeated measures. Additional assessments included instantaneous Total Nasal Symptom Score, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, reflective Total Ocular Symptoms Score, instantaneous Total Ocular Symptoms Score, individual symptoms, Physician-assessed Nasal Symptom Score, and adverse events. ResultsGSP301 showed clinically meaningful and statistically significant improvement in rTNSS vs placebo (−0.6; 95% confidence interval, −0.9 to −0.2; P = .001). Statistically significant improvements favoring GSP301 were shown for all individual rTNSS symptoms, instantaneous Total Nasal Symptom Score, and most of its individual symptoms, Physician-assessed Nasal Symptom Score (P = .01), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (P < .001). For ocular symptoms, numerical improvements favoring GSP301 were observed, with statistical significance achieved only for reflective “tearing/watering eyes” (P = .04). Treatment-emergent adverse events occurred in 12.0% and 10.4% of patients in the GSP301 and placebo groups, respectively. One subject (0.5%) (placebo group) experienced a serious adverse event (suspected viral meningitis) that was not related to the study treatment and was resolved. ConclusionGSP301 was well tolerated and efficacious for treating SAR symptoms in pediatric patients and showed a favorable safety profile.Trial Registration: ClinicalTrials.gov Identifier: NCT03463031.

The epidemiology of aseptic meningitis in New Zealand children from 1991 to 2020.

Aseptic meningitis, including culture negative and viral meningitis, contributes a significant health-care burden, including unnecessary antibiotic use and hospitalisation to treat possible bacterial meningitis. This study analysed aseptic meningitis hospitalisations in New Zealand (NZ) children over 29 years. In this population-based study, aseptic meningitis hospitalisations in NZ children <15 years old were analysed from 1991 to 2020. Incident rate ratios were calculated using Poisson regression models. Variations in hospitalisations by age, year, sex, ethnicity, geographical region and socio-economic deprivation were analysed. There were 5142 paediatric aseptic meningitis hospitalisations from 1991 to 2020. Most were unspecified viral meningitis (64%), followed by enterovirus (29%). Hospitalisation rates varied annually with a median of 18.4/100 000 children including a peak in 2001 of 56.4/100 000 (51.7-61.6). From 2002 to 2019, rates increased by 8.4%/year (7.2-9.5%) in infants <90 days old but decreased in all other age groups. In 2020, a reduction in hospitalisations to 9.6/100 000 (7.9-11.8) occurred, and in infants <90 days old were 0.37 times expected. Hospitalisations were 1.50 times (1.49-1.68) higher in males than females; higher in children of Māori (P< 0.001) and Pacific (P< 0.001) versus European ethnicity; and higher for children living in the most (2.44 times, (2.16-2.75)) versus least deprived households; and in northern versus southern NZ. Aseptic meningitis hospitalisations increased in young infants during 29 years of surveillance, apart from 2020 when admissions reduced during the COVID-19 pandemic. In contrast, hospitalisations decreased in children aged >1year. Further investigation into reasons for higher admissions by ethnic group, geographical location and increased deprivation are required.

A Review on Headaches Due to COVID-19 Infection.

Since December 2019, the time when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spotted, numerous review studies have been published on COVID-19 and its neuro invasion. A growing number of studies have reported headaches as a common neurological manifestation of COVID-19. Although several hypotheses have been proposed regarding the association between headache and the coronavirus, no solid evidence has been presented for the mechanism and features of headache in COVID-19. Headache also is a common complaint with the omicron variant of the virus. COVID-19 vaccination also is a cause of new-onset headaches or aggravation of the previous headache in migraine or tension headache sufferers. In this review study, the types of headaches reported in previous studies and their possible pathogenic mechanisms are outlined. To accomplish this objective, various types of headaches are classified and their patterns are discussed according to ICHD-3 diagnostic criteria, including, headaches attributed to systemic viral infection, viral meningitis or encephalitis, non-infectious inflammatory intracranial disease, hypoxia and/or hypercapnia, cranial or cervical vascular disorder, increased cerebrospinal fluid (CSF) pressure, refractive error, external-compression headache, and cough headache. Then, their pathogeneses are categorized into three main categories, direct trigeminal involvement, vascular invasion, and inflammatory mediators. Furthermore, persistent headache after recovery and the predictors of intensity is further investigated. Post-vaccination headache is also discussed in this review.

10-Year Retrospective Review of the Etiologies for Meningitis With Elevated Adenosine Deaminase in Cerebrospinal Fluid: Etiologies Other Than TB.

PurposeAn elevated adenosine deaminase (ADA) level in the cerebrospinal fluid (CSF) is considered a reliable marker of tuberculous meningitis (TBM). However, CSF-ADA levels can also be elevated in other diseases. We aimed to find the most common diagnosis of patients with elevated CSF-ADA levels for the last 10 years.MethodsWe retrospectively investigated the diagnoses of all patients with elevated CSF-ADA (ADA ≥ 10 IU/L) levels between 2010 and 2019 at the Samsung Medical Center. Definite TBM was defined based on microbiological evidence. Clinical TBM was defined based on the brain imaging and response to the standard TB treatment. We compared the laboratory characteristics of the three most common diagnoses.ResultsCSF-ADA levels were elevated in 137 (5.6%) of 2,600 patients. The most common diagnoses included hematologic malignancy (HM; n = 36, 26.2%), TBM (n = 26, 19.0%), and viral meningitis (VM; n = 25, 18.2%). CSF-ADA levels did not differ significantly between TBM [median (interquartile range (IQR)), 20.2 IU/L (13.8–29.3)] and HM [16.5 (12.8–24.0)]. However, CSF-ADA levels were lower in VM [14.0 (11.0–16.1)] than in TBM (p = 0.027). Lymphocyte-dominant pleocytosis was more common in VM [77.0% (70.8–81.5)] than in TBM [16.0 (3.0–51.0), p = 0.015] or HM [36.0 (10.0–72.0); p = 0.032]. Interestingly, the CSF characteristics of clinical TBM were similar to those of VM but not definite TBM.ConclusionThe most common diagnoses with elevated CSF-ADA levels were HM, followed by TBM and VM. Clinicians should carefully consider the differential diagnoses in patients with elevated CSF-ADA levels, especially those in the early stage of meningitis without microbiological evidence for TBM.