Impact of the COVID-19 Outbreak on Aseptic Meningitis in Children.

Objectives: Viruses are the most common infectious causes of aseptic meningitis (AM). After the COVID-19 pandemic, AM following the COVID-19 disease and its different vaccines were reported. This study compares some characteristics of patients with AM before and after the COVID-19 pandemic. Materials & Methods: This retrospective cross-sectional study analyzed patients' demographic and laboratory data (one month to 14 years old) with AM from March 2018 to March 2022. The first period involves two years before the COVID-19 outbreak (March 2018 to March 2020). The second period starts with the COVID-19 pandemic (from March 2020 until March 2022). Results: A significant decrease was observed in the frequency of patients admitted with AM after the COVID-19 pandemic in the referral children's hospital in Qazvin. The incidence of AM in children older than five decreased significantly, and as a result, the average age of patients with this diagnosis decreased, too. A meaningful decline in the prevalence of AM in the summer and fall seasons has been observed. Conclusion: After the COVID-19 outbreak, the incidence of AM in children significantly decreased. Implementing the hygienic recommendations for inhibiting COVID-19 virus transmission also protected children from the spread of other viruses.

Mild Encephalopathy/Encephalitis With Reversible Splenial Lesion Associated With Meningitis Related to Mumps Disease: An Unusual Presentation in a Male Adult.

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is characterized by mild neurological manifestations associated with spontaneously reversible lesions of the splenium of the corpus callosum. While various conditions and diseases can trigger MERS, infectious causes predominate, with mumps being notably linked to MERS in the pediatric population. Although rare in adults, there are sporadic case reports associating mumps with MERS. Here we report a 23-year-old male patient with a typical presentation of mumps who presented with meningeal syndrome, dizziness, seizures, and right orchitis. Brain MRI showed classic findings of MERS syndrome while cerebrospinal fluid analysis demonstrated lymphocytic pleocytosis. Our patient had a confirmed diagnosis of mumps disease with multiple complications, including MERS, meningitis, and orchitis, and was managed with symptomatic medications and antiviral therapy. Subsequently, there was a gradual resolution of these manifestations and the outcome was favorable, with no residual sequelae.

New Insights Into the Therapeutic Management of Varicella Zoster Virus Meningitis: A Series of 123 Polymerase Chain Reaction-Confirmed Cases.

Background: Varicella zoster virus (VZV) can reactivate and cause meningitis, but few studies have distinguished it from meningoencephalitis regarding treatment recommendations.The objective of this study was to assess the outcomes of a large series of patients with VZV meningitis according to their therapeutic management. Methods: We conducted a bicentric retrospective cohort study, in Paris, France, including all adult patients with a cerebrospinal fluid sample positive for VZV by polymerase chain reaction between April 2014 and June 2022. We distinguished meningitis from encephalitis according to the International Encephalitis Consortium criteria. Unfavorable outcome was defined as mortality or functional sequelae defined by a loss of 2 points on the modified Rankin Scale. Results: We included 123 patients with meningitis. Among them, 14% received no antivirals, while 20% were treated with oral valacyclovir alone, 41% with a short course of intravenous (IV) acyclovir before switch to valacyclovir, and 25% with a long course of IV acyclovir. Outcomes were favorable regardless of antiviral regimen. In multivariate analysis, only age, underlying immunosuppression, and cranial radiculitis appear to be predictive factors for longer IV therapy, based on the Akaike information criterion. Conclusions: In this study, patients with VZV meningitis had a good outcome, with no evidence of any impact of the treatment strategy. However, further studies are needed to support the possibility of milder treatment in immunocompetent patients, avoiding cost and side effects of IV acyclovir.

Antibodies in Aseptic Meningitis of Connective Tissue Disorder: A Case Report.

Mixed connective tissue disorder (MCTD) is the first overlap syndrome described with features of overlapping manifestations of at least two other autoimmune rheumatic conditions. It is an autoimmune disease of rarity and is strongly associated with specific antibodies to U1 small nuclear ribonucleoprotein (anti-U1-RNP). This disorder affects almost all organs of the body, and it has varied clinical presentations as it has an autoimmune and inflammatory background, causing heightened immune cell activation. They present more commonly with less fatal symptoms like joint pain, stiffness, and mucocutaneous changes. The majority present initially with Raynaud's phenomenon followed by muscular skeletal involvement and around half of them present with swallowing problems due to esophageal dysmotility. Rarely do they also present with more morbid symptoms of pulmonary hypertension and central nervous system involvement. MCTD on follow-up had a 10 percent association with neurological manifestations as reported by the National Organization for Rare Diseases (NORD), and the most reported diseases were trigeminal neuralgia and aseptic meningitis. Patients presenting with such symptoms and, when treated only with guideline-based antibiotics therapy, would delay the treatment, leading to a poorer prognosis. The following is an interesting case of a young female presenting with a headache, which was masquerading as an underlying undiagnosed connective tissue disorder. Headache is a predominant presentation that has several etiologies in autoimmune disease and meticulous differential diagnosis workup is a must. This case highlights the fact that any persistent atypical, unusual symptom needs to be always considered for further evaluation to arrive at a diagnosis and for a favorable outcome.

Prospective randomized trial comparing relapse rates in dogs with steroid-responsive meningitis-arteritis treated with a 6-week or 6-month prednisolone protocol.

BACKGROUND: Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life. HYPOTHESIS/OBJECTIVES: Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6-month prednisolone protocol and a 6-week protocol. ANIMALS: Forty-four hospital cases from multiple referral centers in the United Kingdom (2015-2019). Twenty of 44 were treated with the 6-month protocol and 24/44 with the 6-week protocol. METHODS: Prospective, randomized trial with 12-month follow-up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling. RESULTS: All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6-month protocol and 9/24 (38%) of the 6-week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40-4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61-3.48; P = 0.40). CONCLUSIONS AND CLINICAL IMPORTANCE: "Short" 6-week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects.

Kikuchi disease complicated with aseptic meningitis following COVID-19 Vaccination: a case report.

BACKGROUND: Kikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical lymphadenopathy. It can mimic many sinister diseases such as lymphoma, tuberculosis, and systemic lupus erythematosus. Aseptic meningitis due to Kikuchi disease is extremely rare, and majority were reported from Japan. There have been no published cases of aseptic meningitis due to Kikuchi disease in Sri Lanka. CASE PRESENTATION: A 29 years old Sri Lankan female presented with a prolonged fever for three weeks with an associated headache for five days duration. She developed painful cervical lymphadenopathy during the hospital stay. She has been previously well and had been vaccinated against COVID-19 six weeks before. Her lumbar puncture showed lymphocytic pleocytosis with marginally elevated protein levels and reduced ratio of serum to CSF sugar. Lymph node biopsy was consistent with necrotizing lymphadenitis. She was subsequently diagnosed with Kikuchi disease complicated with aseptic meningitis. She responded to corticosteroids well and had an uneventful recovery. CONCLUSION: Kikuchi disease is a rare self-limiting disorder that can be complicated with aseptic meningitis on infrequent occasions. Other conditions such as tuberculosis, lymphoma, systemic lupus erythematosus, and adult-onset Still's disease should be considered as differential diagnoses. Knowledge of Kikuchi disease and its complications will prevent unnecessary investigations which delay the early diagnosis and treatment.

A Case of Ketorolac-Induced Aseptic Meningitis.

Drug-induced aseptic meningitis is a rare condition that occurs because of an adverse reaction to medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Unlike bacterial or viral meningitis, aseptic meningitis is not caused by an infection, but rather by an inflammatory response. This condition creates a challenge since patients with aseptic meningitis often present with classic clinical meningeal symptoms, including fever, headache, and neck stiffness. We present a case of a patient with NSAID-induced aseptic meningitis and highlight the importance for healthcare providers to have a high index of suspicion for drug-induced aseptic meningitis in patients presenting with symptoms of meningitis with negative cerebrospinal fluid analysis and culture.

Case of Immune Checkpoint Inhibitor Induced Myasthenia Gravis.

An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then switched to nivolumab and ipilimumab in view of sorafenib intolerance and disease progression. Subsequently, he developed dysphagia and generalized dyspnea culminating in hypercapnic respiratory failure requiring intubation. After an extensive workup, the etiology of his fluctuating respiratory issues was narrowed down to a likely neuromuscular process. Although antibodies to acetylcholine receptors (anti-AChR Ab) were negative, he was treated with high-dose steroids due to clinical concern for Immune Checkpoint Inhibitor (ICI) neurotoxicity. His recovery post immune suppression and absence of recurrence after ICI cessation suggested the possibility of this being an ICI neurotoxicity manifesting with myasthenic symptoms. Incidentally, he also had evidence of aseptic meningitis on cerebrospinal fluid analysis further strengthening this diagnosis. This case illustrates the importance of early recognition of ICI toxicity which will in turn lead to initiating treatments sooner and also decreasing the length of illness.

Intravenous Immunoglobulin-Induced Aseptic Meningitis in a Dermatomyositis Patient.

Aseptic meningitis is a rare but serious complication of treatment with intravenous immunoglobulin (IVIG) and often mimics meningitis of infectious etiology which poses a challenge for timely diagnosis. Although there are published recommendations on the management of IVIG-induced complications, there are no clear guidelines on the continuation of IVIG use after resolution of aseptic meningitis. We present a case of IVIG-induced aseptic meningitis in a patient with a history of refractory dermatomyositis who had been treated with immunosuppressive therapy and IVIG infusions for over a year. The patient developed intense head and neck pain with associated photophobia 24 hours after the most recent IVIG infusion. The patient was managed with supportive care consisting of intravenous fluids and analgesics. The patient's aseptic meningitis resolved without neurological complications. Ultimately, the patient was restarted on IVIG due to the recurrence of weakness from dermatomyositis. The patient tolerated re-initiation of IVIG without recurrence of IVIG-induced complications. This case highlights the importance of considering IVIG-induced aseptic meningitis as a differential diagnosis in evaluating patients with non-infectious meningitis even after regular IVIG infusions. This case also demonstrates that it is safe to reinitiate IVIG after the resolution of IVIG-induced aseptic meningitis.

Acute Aseptic Meningitis Temporally Associated with Intravenous Polyclonal Immunoglobulin Therapy: A Systematic Review.

An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Leptomeningeal Dissemination Complicated With Acute Tetraplegia From a Supratentorial Multicentric Isocitrate Dehydrogenase (IDH)-Wildtype Glioblastoma: A Case Report.

Glioblastoma (GBM) is a major concern for neurosurgeons and oncologists, being a malignant tumor with a high recurrence rate and reduced survival. Leptomeningeal dissemination (LMD) of GBM is rare and difficult to diagnose due to the low rate of cellular detection in the cerebrospinal fluid and clinical and imaging similarities with fungal and tuberculous meningitis. We report the case of a 25-year-old female patient suffering from multicentric GBM who developed hydrocephalus and extensive LMD three months after surgery for a left frontal parafalcine cerebral GBM isocitrate dehydrogenase (IDH)-wildtype.

Elderly Woman With No Autoimmune Disease With Aseptic Meningitis Caused by Celecoxib.

Nonsteroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis (NIAM) is frequently reported in patients with autoimmune disease. Ibuprofen-induced NIAM is the most common case report of NIAM. We report a patient without autoimmune disease who developed NIAM following oral celecoxib administration. A literature review and survey of cases registered in the Japanese Adverse Drug Event Report (JADER) database is also provided. A 73-year-old woman with no autoimmune disease developed a headache the day after taking celecoxib, and NIAM was suspected. The headache resolved quickly following celecoxib discontinuation. Although lumbar puncture was not available in this case, bacterial or viral meningitis was negative, and NIAM could not be ruled out. This case involved an older adult patient without an autoimmune disease, with celecoxib as the causative NSAID. A literature review found numerous cases of autoimmune diseases in younger patients. To date, only one case of celecoxib-induced NIAM has been reported. Analysis of NIAM cases in JADER revealed an onset time of approximately three days. JADER analysis indicated that NIAM tended to occur immediately after administration, although the onset with cyclooxygenase-2 selective agents might be slower.

EBV-associated CNS infection in an immunocompetent adult: A case report and literature review.

EBV infections rarely cause CNS involvement. For young adult patients with suspected CNS infection, bacterial and other common viral infections should be excluded first and treated empirically until proven otherwise. Challenges in diagnosing EBV-associated CNS infection, emphasizing the role of CSF PCR in confirming the diagnosis.

Metatranscriptomics revealed the molecular characterization of circulating enterovirus strains causing aseptic meningitis in children in Wuxi, China.

Enteroviruses are major etiological agents of aseptic meningitis globally, however information on circulating enterovirus types associated with this disease in Wuxi, China is limited. In this study, cerebrospinal fluid samples were collected from 20 pediatric aseptic meningitis cases in a Wuxi hospital in 2020 and subjected to metagenomic analysis to detect pathogens. Enterovirus B was detected in 9 cases, including 7 echovirus 18 (E18) and 2 echovirus 11 (E11) strains. The E18 strains exhibited 87.5-98.2% nucleotide identity and phylogenetically clustered with other China E18 strains, while the E11 strains showed 97.59% identity and clustered within the D5 subgroup along with other China E11 strains. One E18 strain was identified as a novel recombinants with a distinct recombination breakpoint within 3D gene. These findings expand knowledge on enteroviruses associated with pediatric aseptic meningitis in Wuxi, and highlight the circulation of genetically diverse E18 and E11 strains, including novel E18 recombinants. Characterization of enterovirus diversity by metagenomic analysis is important for molecular diagnosis and epidemiological tracking of aseptic meningitis cases. Continued surveillance of circulating enterovirus strains in Wuxi that may cause future outbreaks is warranted.

Human Enterovirus B Is a Significant Cause of Aseptic Meningitis and Sepsis-Like Illness in Young Infants in Thailand.

Human enterovirus (EV) and Parechovirus (PeV) infections are major causes of sepsis-like illness in infants < 90 days of age. Enterovirus species B (EV-B) was found to be the leading cause of aseptic meningitis in young infants. In Thailand, EV and PeV are not part of the routine screening of blood or cerebrospinal fluid (CSF) of children with suspected aseptic meningitis and sepsis-like illness. Consequently, data on EV and PeV epidemiology are limited. This study tested clinical samples from hospitalized young infants with suspected aseptic meningitis or sepsis-like illness between 2013 and 2022 for EV, PeV, and Herpes simplex virus (HSV). Of 95 specimens, 10 were positive for EV, representing 10.5%. These positive samples included eight CSF and two stool samples. No samples were positive for PeV and HSV. Of these positive cases, EV-B was detected in eight, and EV-A was detected in two cases. The species of EV-B detected include echovirus-18 (E18) (n=2), E21 (n=2), E4(n=1), E5 (n=1), E9 (n=1), and E11 (n=1). Our report demonstrates the significant role of EV-B, and less frequently EV-A, in Thai infants with aseptic meningitis and sepsis-like illness.

Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.

Meningitis-Retention Syndrome as an Unrecognized Clinical Condition in Indian Scenario: Fall Through the Cracks.

Meningitis-retention syndrome (MRS) is a recently recognized condition marked by the concurrent occurrence of aseptic meningitis with acute urinary retention. We present the case of a 22-year-old man who presented with an undiagnosed fever with headache and urinary retention. Subsequent urodynamic testing revealed an underactive detrusor, resulting in insufficient contraction of the bladder during voiding despite normal sensation during bladder filling. Normal urinary voiding was successfully restored without the need for treatment within a 30-day timeframe. It is crucial to include MRS in the differential diagnosis of acute urinary retention. It is crucial to include MRS in the differential diagnosis of acute urinary retention. Despite the generally benign and self-remitting nature of MRS, the management of acute urinary retention is necessary.

Distinct patterns of postoperative fever in paediatric neurosurgery patients.

PURPOSE: Postoperative fever is a common problem following neurosurgery but data on the causes among paediatric patients is sparse. In this report, we determined the incidence, causes, and outcomes of postoperative fever in paediatric neurosurgical patients (< 18 years), and contrasted the findings with an adult cohort published recently from our unit. METHODS: We recruited 61 patients who underwent 73 surgeries for non-traumatic neurosurgical indications over 12 months. A standard protocol was followed for the evaluation and management of postoperative fever. We prospectively collected data pertaining to operative details, daily maximal temperature, clinical features, and use of surgical drains, urinary catheters, and other adjuncts. Elevated body temperature of > 99.9 °F or 37.7 °C for > 48 h or associated with clinical deterioration or localising features was considered as "fever"; elevated temperature not meeting these criteria was classified as transient elevation in temperature (TET). RESULTS: Twenty-six patients (35.6%) had postoperative fever, more frequent than in adult patients. TET occurred in 12 patients (16.4%). The most common causes of fever were aseptic meningitis (34.6%), followed by urinary tract infections (15.4%), pyogenic meningitis, COVID-19, and wound infections. Postoperative fever was associated with significantly longer duration of hospital admission and was the commonest cause of readmission. CONCLUSION: In contrast to adults, early temperature elevations in paediatric patients may portend infectious and serious non-infectious causes of fever, including delayed presentation with aseptic meningitis, a novel association among paediatric patients. Investigation guided by clinical assessment and conservative antibiotic policy in keeping with the institutional microbiological profile provides the most appropriate strategy in managing paediatric postoperative fever.

Aseptic meningitis following spinal anaesthesia: An uncommon and challenging diagnosis.

Drug-induced aseptic meningitis (DIAM) or chemical meningitis following spinal anaesthesia has rarely been reported. DIAM is caused by meningeal inflammation due to intrathecally administered drugs or secondary to systemic immunological hypersensitivity. We hereby present a case of a young adult with aseptic meningitis following neuraxial anaesthesia possibly provoked by bupivacaine. The initial cerebrospinal fluid (CSF) picture revealed neutrophilic pleocytosis and normal glycorrhachia. CSF culture was negative. The patient was put on invasive mechanical ventilation and started on intravenous antibiotics. There was a rapid improvement in clinical condition without any residual neurological deficit within the next few days. Aseptic meningitis following neuraxial anaesthesia can be prevented by strict aseptic protocols and careful inspection of visible impurities while administering the intrathecal drug. Detailed history taking, clinical examination, and focused investigations can distinguish between bacterial and chemical meningitis. Appropriate diagnosis of this entity may guide the treatment regimen, reducing hospital stay and cost.