Echovirus 18 has been recognized as an important causative pathogen of aseptic meningitis in young children worldwide, and echovirus 18-induced meningitis is rarely found in adults with immunocompetence. In this case study, we report the clinical and virological characteristics of aseptic meningitis caused by recombinant echovirus 18 in an adult with immunocompetence. A 31-year-old woman with immunocompetence was admitted to our hospital with fever, dizziness, severe headache, nausea, and vomiting for the past 1 day and was diagnosed with viral meningitis based on the clinical manifestations and laboratory results from cerebrospinal fluid (CSF). The patient received antiviral treatment with ribavirin and interferon as soon as the enterovirus infection was identified using qRT-PCR and was cured after 4 days. From the oropharyngeal swab and CSF samples, two echovirus 18 strains were isolated with a single nucleotide difference located at the 5' UTR. Phylogenetic analyses based on the VP1 gene showed that the two strains belonged to the subgenotype C2 and were clustered with sequences obtained from China after 2015, while the results from the 3D polymerase region showed that the two strains were closely related to the E30 strains. Bootscanning results using the 5' UTR to 2A region and the 2B to 3' UTR region showed that potential intertypic recombination had occurred in the 2B gene. Recombination analyses further confirmed that the two strains (echovirus 18) presented genome recombination with echovirus 30 in the nucleotide regions of the 2B gene. To the best of our knowledge, this is the first report of echovirus 18-induced meningitis in an adult with immunocompetence from mainland China, highlighting the need for close surveillance of echovirus 18 both in children and adults in the future.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), such as neurological toxicity. A 46-year-old man was diagnosed with squamous cell lung cancer. Lung cancer recurred 3 years after he experienced left segmental lung rejection. Therefore, he received atezolizumab as fourth-line chemotherapy. He experienced fever, headache, and decreased consciousness 10 days after the first dose of atezolizumab. Plain head computed tomography and cerebrospinal fluid examination showed no significant findings. Magnetic resonance imaging (MRI) with a Gadolinium (Gd)-enhanced Cube fluid-attenuated inversion recovery (FLAIR) sequence showed nodular abnormalities with contrast enhancement. Thus, aseptic meningitis caused by ICIs was suspected. His consciousness level gradually improved with glucocorticoid therapy. Moreover, most nodular abnormalities observed on cerebral MRI disappeared concurrently. Thus, Gd-enhanced Cube FLAIR sequence has the unique ability to reveal immune-related aseptic meningitis.

Aseptic meningitis is diagnosed using clinical and laboratory findings of meningeal inflammation in the absence of bacteria in cerebrospinal fluid smear and culture. It is commonly caused by a viral infection, and most cases are improved without specific treatment. We present a case of aseptic meningitis in a 33-year-old Japanese man that was diagnosed only after a repeat lumbar puncture. The patient had a positive ocular globe compression sign with no other positive meningeal signs. This case highlights the importance of repeated lumbar puncture in patients with suspected aseptic meningitis if the initial lumbar puncture results are negative, and there is a clinical value in assessing the ocular globe compression sign, particularly when other clinical signs of meningitis are absent.

Mollaret meningitis is a recurrent aseptic meningitis mostly caused by herpes simplex virus type 2. Other causes of the disease rarely exist, and its pathology is not well understood. Herein, we present a 57-year-old man who had been admitted to our hospital eight times with recurrent aseptic meningitis. Although the deoxyribonucleic acid (DNA) of varicella-zoster virus (VZV) was not detected in the cerebrospinal fluid (CSF), his genetic analysis, measurement of anti-VZV immunoglobulin-G (IgG) in the CSF, the VZV IgG index, IgG in the serum, and interleukin-1 beta in the CSF revealed that the Mollaret meningitis had been caused by the VZV. This case demonstrates that Mollaret meningitis can be caused by the VZV when specific factors are associated with decreased immune response. This case is valuable in elucidating the pathophysiology of Mollaret meningitis.

Aseptic meningitis is a known but unusual serious adverse effect of intravenous immunoglobulin (IVIG). It usually resembles infectious meningitis, which makes its diagnosis challenging. In this report, we present the case of a five-and-a-half-year-old Chinese girl with juvenile dermatomyositis (JDM) who presented with signs of meningismus 21 hours after the initiation of IVIG infusion. Her blood work at diagnosis showed neutrophilia and lymphopenia. The cerebrospinal fluid (CSF) analysis demonstrated neutrophilic pleocytosis, hyperproteinorrachia, and normoglycorrhachia. All microbiological tests were negative. The child fully recovered within 72 hours without neurological sequelae. IVIG-induced aseptic meningitis remains a diagnosis of exclusion. Although it is rare, pediatricians should be aware of this complication and avoid unnecessary investigations or treatment.

A transsphenoidal surgical (TSS) approach is used for pituitary gland surgery involving pituitary adenomas, as well as for the biopsy of various neurosurgical tumors. TSS, although a relatively safe procedure, can lead to complications like hypopituitarism, visual impairment, nasal septal perforation, diabetes insipidus, carotid artery injury, and cerebrospinal fluid (CSF) leaks. Aseptic meningitis is also one of the complications of this procedure with an incidence of 1-2%, presenting with symptoms similar to bacterial meningitis, but with a low-grade fever of <102 F or even apyrexia. Here, we present a rare case of aseptic meningitis due to CSF leakage, presenting after 20 years of endoscopic surgery. A ventriculoperitoneal shunt was placed to stem the leak after two unsuccessful attempts of endonasal repair.

Aseptic meningitis is a rare life-threatening complication of primary Sjögren's syndrome (pSS) and its characteristics and prognosis remain unknown. We present our case of aseptic meningitis associated with pSS and reviewed the published literature to elucidate their characteristics and prognosis. An 84-year-old man was admitted to our hospital for fever and disturbance of consciousness. Acute aseptic meningitis was diagnosed based on the results for cerebrospinal fluid and head imaging tests. As an etiological investigation for his aseptic meningitis, serum anti-SSA and anti-SSB antibodies were found to be positive and the biopsy specimen of his labial salivary gland revealed a lymphocytic sialadenitis, confirming a diagnosis with pSS. Treatment with moderate-dose glucocorticoid completely improved his aseptic meningitis. Relapse of the disease was not observed during his clinical course over 12 months. Our present case and literature review suggest that aseptic meningitis can be an initial manifestation of pSS and treatable by immunosuppressive therapy. Thus, early recognition and treatment initiation are critical to prevent irreversible damage of central nerve system in pSS-associated aseptic meningitis. In aseptic meningitis of unknown origin, pSS should be included in differential diagnoses, and testing for serum anti-SSA and anti-SSB antibodies may be useful as an initial screening.

As the use of COVID-19 vaccines gains more prevalence, rare and uncommon side effects are reported in the medical literature. This is a case report of a 75-year-old male patient who presented on the second day after receiving the Moderna Bivalent mRNA COVID-19 booster vaccine with abrupt onset behavioral changes and global aphasia with no focal deficits. Stroke and infectious meningitis/encephalitis were ruled out. Signs of aseptic inflammation were seen on cerebrospinal fluid (CSF) analysis. Workup for autoimmune and paraneoplastic encephalitis was unyielding. The observation of rapid clinical improvement prompted watchful waiting that concluded in the resolution of clinical manifestations within less than a week of onset. This case is reported to support the currently limited knowledge of rare neurological sequelae of mRNA vaccine and is in line with recently published few cases that suggest vaccine-related encephalitis.

Flaviviruses are a heterogeneous group of viruses that may induce broad antigenic cross-reactivity. We present a patient who was admitted to the infectious disease department with symptoms suggestive of aseptic meningitis. During the clinical workup, the patient reported a tick bite two weeks before the disease onset. High titers of IgM and IgG antibodies to tick-borne encephalitis virus (TBEV) were found in both serum and cerebrospinal fluid (CSF) samples, indicating acute TBEV infection. West Nile virus (WNV) and Usutu virus (USUV) IgM and/or IgG antibodies were also detected, and a virus neutralization test (VNT) was performed. A high titer of TBEV neutralizing (NT) antibodies (640) was detected, which confirmed acute TBE. However, NT antibodies to WNV and USUV were also detected (titer 80 for both viruses). After TBEV and WNV IgG avidity evaluation, previous flavivirus infection was highly suspected (avidity index 82% and 89%, respectively). Blood, CSF, and urine samples were negative for respective viruses' RNA. The presented case highlights the challenges in flavivirus serodiagnosis. In the published literature, different degrees of cross-reactivity or cross-neutralization between TBEV and dengue, louping ill, Omsk hemorrhagic fever, Langat, and Powassan virus were also observed. Therefore, the serology results should be interpreted with caution, including the possibility of cross-reactivity. In areas where several flaviviruses co-circulate VNT is recommended for disease confirmation.

Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

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 half is a weak predictor of bacterial meningitis due to the small contribution of bacteria as a cause among enteroviruses and aseptic etiologies.

The patient was a 32-year-old man with no HIV infection and possible syphilis infection at the age of 22 years. At the age of 29 years, he visited an ophthalmologist for diplopia due to right oculomotor nerve palsy. He underwent diplopia strabismus surgery for unexplained oculomotor nerve palsy. At the age of 31 years, he had a left oculomotor nerve palsy and was referred to our department. He was diagnosed with neurosyphilis based on positive serum and cerebrospinal fluid syphilis antibodies. MRI showed aneurysm, asymptomatic cerebral hemorrhage, and contrast enhancement of the left oculomotor nerve, leading to the diagnosis of meningovascular syphilis. The patient's symptoms improved with penicillin and corticosteroids. The oculomotor nerve palsy may be due to microcirculatory disorder caused by syphilitic cerebral endarteritis.

The aim of this study was to evaluate the role of viral polymerase chain reaction (PCR) testing in patients with aseptic meningitis and identify opportunities for improvement in clinical management. All cerebrospinal fluid samples collected in 1 year from four teaching hospitals in Sydney, Australia, were reviewed. Patients with aseptic meningitis were selected, and clinical and diagnostic features, hospital length of stay (LOS), and treatment were analyzed. Identifying a cause by viral PCR did not reduce hospital LOS (median 3 days) or antibiotic use (median 2 days), but the turnaround time of the PCR test correlated with LOS (Rs = 0.3822, p = 0.0003). Forty-one percent of patients received intravenous acyclovir treatment, which was more frequent in patients admitted under neurologists than infectious diseases physicians (56% vs. 24%; p = 0.013). The majority of patients did not have investigations for alternative causes of aseptic meningitis such as human immunodeficiency virus and syphilis if the viral PCR panel was negative. The benefit of PCR testing in aseptic meningitis in adults in reducing LOS and antibiotic use is unclear. The reasons for unnecessary aciclovir use in meningitis syndromes require further assessment.

Reactivation of latent human herpesvirus 2 (HHV-2) can cause spontaneous recovering aseptic meningitis and recurrent meningitis in adults, but it rarely affects the brain parenchyma to cause encephalitis. Here, we report the case of a 37-year-old male patient admitted to our hospital due to fever with a progressive headache for 3 days and paroxysmal episodes of unconsciousness for 1 day. Brain magnetic resonance imaging (MRI) revealed viral meningoencephalitis. Then, metagenomics next-generation sequencing (mNGS) was applied, which detected 12,024 unique sequences of HHV-2 in cerebrospinal fluid (2022), indicating HHV-2 encephalitis. After antiviral treatment, the patient's symptoms improved, and he was discharged. During the 1-month follow-up, the patient recovered without any new symptoms, but a brain MRI revealed significant atrophy of the original foci. The patient was finally diagnosed with HHV-2 necrotizing meningoencephalitis, which is extremely rare. mNGS helped with the clinical diagnosis and strengthened our understanding of HHV-2 infections in the central nervous system.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by disordered immune activation resulting in cytokine storm and inflammation. We present a 27-year-old woman who had a fever and diffuse rash after recently starting lamotrigine. She developed meningismus and polyarthralgia. Laboratory results revealed cytopenia, elevated serum aminotransferases, hypofibrinogenemia and elevated ferritin. Cerebrospinal fluid analysis suggested aseptic meningitis. Antinuclear antibody and rheumatoid factor serologies were positive, complement levels of C3 were decreased, and antihistone antibody was negative. A bone marrow biopsy demonstrated hemophagocytic macrophages and the diagnosis of HLH was made. The patient was empirically started on high-dose intravenous dexamethasone following which both her mental status and laboratory indices markedly improved. Lamotrigine has been shown to induce lupus-like syndrome, aseptic meningitis, and HLH, but not concomitantly. Our patient was recently started on lamotrigine, likely inducing her underlying undiagnosed lupus, in addition to, resulting in aseptic meningitis and a cytokine storm leading to HLH.

Craniopharyngiomas (CPs) are benign tumors that are believed to arise from embryonic remnants of the Rathke pouch epithelium. Herein, we report a case of aseptic meningitis due to spontaneous rupture of multicystic CP, which contained an Ommaya catheter. A 19-year-old boy was admitted to the hospital with a 4-day history of acute severe headache after strenuous physical exercise followed by altered sensorium, fever, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed marked pleocytosis and elevated protein levels. CSF culture was otherwise negative. Cyst reduction on subsequent imaging confirmed the diagnosis. The patient received intravenous steroid therapy and was discharged asymptomatic. This is a rare evolution of a multicystic CP, which was previously treated with intracystic therapy and had an Ommaya catheter. Clinicians should be aware of spontaneous CP rupture and look actively for the occurrence of cholesterol crystals or elevated CSF levels of cholesterol as well as prompt follow-up imaging.

An 83-year-old man underwent head computed tomography (CT) to investigate cognitive decline and gait disturbance and was admitted to undergo a cerebrospinal fluid (CSF) tap test for suspected idiopathic normal-pressure hydrocephalus. He had a history of chemotherapy for mantle cell lymphoma (MCL), but CT on admission showed no evidence of recurrence. After admission, his level of consciousness rapidly deteriorated and CSF examination suggested infiltration of MCL into the central nervous system (CNS). Although CNS involvement in MCL is rare, this case demonstrates that even if recurrence of MCL is not suspected based on CT findings.

Meningitis is the inflammation of the meninges with an associated abnormal cell count in the cerebrospinal fluid (CSF). Aseptic meningitis, defined by the lack of bacterial growth in cultures, is the most common form, with viruses being a frequent cause. Viral causes of meningitis have become more common as the prevalence of bacterial meningitis has decreased due to vaccinations, and viral meningitis is the most common form of meningitis in many countries. Viral meningitis typically presents with the acute onset of fever, headache, photophobia, neck stiffness, and often nausea and vomiting, although younger children may not show signs of meningeal irritation.  Appropriate and timely evaluation is critical as there are no reliable initial clinical indicators to differentiate bacterial and viral etiologies of meningitis. Viral meningitis is usually a self-limiting illness with a good prognosis.