Six Year Old With Chronic Headache: An Unexpected Meningitis Mimic.

The constellation of fevers accompanied by headache and vomiting is a red flag for clinicians that appropriately triggers evaluation for meningitis and other life-threatening diagnoses. When symptoms persist even after these conditions are ruled out, patient care becomes more challenging. We present the case of a 6-year-old male with a history of autism spectrum disorder who presented with 6 months of headaches and associated vomiting and intermittent fevers with negative infectious workup despite cerebrospinal fluid pleocytosis. Serial neuroimaging and laboratory evaluation ultimately led to a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) presenting as aseptic meningitis. The clinical and radiographic findings of MOGAD are widely variable and overlap with several other inflammatory conditions, which makes diagnosis challenging. This case highlights the importance of recognizing this rare MOGAD presentation as an infectious meningitis mimic.

Neonatal sepsis with meningitis, ventriculitis and brain abscess caused by Edwardsiella tarda.

A case of neonatal sepsis caused by Edwardsiella tarda, an uncommon pathogen typically associated with aquatic lifeforms, is described. The infant presented in septic shock with seizures and respiratory failure and was found to have meningitis, ventriculitis and a brain abscess requiring drainage. Only a small number of case reports of neonatal E. tarda infection, several with sepsis with poor auditory or neurodevelopmental outcomes or meningitis, have been described in the literature. This case report suggests that E. tarda, while uncommon, can be a cause of serious central nervous system disease in the neonatal population and that an aggressive approach to pursuing and treating complications may lead to improved neurodevelopmental outcomes.

Streptococcus intermedius causing primary bacterial ventriculitis in a patient with severe periodontitis - a case report.

BACKGROUND: Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously. CASE PRESENTATION: A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient's condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month. CONCLUSIONS: Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.

Three-year follow-up of rheumatoid meningitis with matrix metalloprotease-9 levels in the serum and cerebrospinal fluid as indicators of disease activity: A case report.

Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis.

Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.

Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China.

BACKGROUND: Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited. METHODS: In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E). RESULTS: In total, 152 patients diagnosed with clinically suspected M/E at four tertiary hospitals were enrolled; ptNGS and mNGS were used in parallel for pathogen detection in CSF. Among the 89 patients who were diagnosed with definite infectious M/E, 57 and 39 patients had causal microbial detection via ptNGS and mNGS, respectively. The overall accuracy of ptNGS was 65.1%, with a positive percent agreement (PPA) of 64% and a negative percent agreement (NPA) of 66.7%; and the overall accuracy of mNGS was 47.4%, with a PPA of 43.8% and an NPA of 52.4% after discrepancy analysis. There was a significant difference in the detection efficiency between these two methods both for PPA (sensitivity) and overall accuracy for pathogen detection (P < 0.05). CONCLUSIONS: NGS tests have provided new information in addition to conventional microbiologic tests. ptNGS seems to have superior performance over mNGS for common causative pathogen detection in CSF for infectious M/E.

[Idiopathic hypertrophic pachymeningitis]. / Idiopaticheskii gipertroficheskii pakhimeningit.

The article presents a case of idiopathic hypertrophic pachymeningitis of a 61-year-old male patient with severe cephalgia and progressive neuropathy of the oculomotor nerves. The diagnosis was confirmed by MRI with gadolinium, which revealed thickening of the dura mater with accumulation of paramagnetic in the convexital parts of the frontal and temporal regions, as well as on the base of the skull and tentorium. During the use of pulse therapy with glucocorticosteroids (GCS) the symptoms regressed, but when the therapy was stopped, there was a relapse of ptosis and oculomotor abnormalities on the other side followed by a slower effect of GCS therapy. The article also presents a brief review of current knowledge about this pathology.

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.

Gnathostoma infection after ingestion of raw fish is a probable cause of eosinophilic meningitis in the Brazilian Amazon.

We report a case of eosinophilic meningitis associated with the ingestion of raw fish (Cichla sp.) from the Brazilian Amazon, likely caused by Gnathostoma. A 36-year-old male visited Juruena river on a fishing trip. After 50 days, the patient presented with an intense frontal headache. A cerebrospinal fluid examination revealed 63% eosinophilia. Another individual who ingested raw fish developed linear dermatitis on the abdominal wall. Anti-Gnathostoma serum antibodies were detected, and the patient made a full recovery after treatment with corticosteroids and albendazole. To date, autochthonous Gnathostoma spp. infections in Latin American countries have only caused linear panniculitis. This report raises awareness of gnathostomiasis-causing meningitis.

[Emergencies in infectious diseases]. / Infektiologische Notfälle.

This article aims to provide an overview of common and high-impact medical emergencies that require prompt and effective infectious diseases management. In the described clinical scenarios of malaria, sepsis, necrotizing fasciitis, and meningitis the authors have emphasized the crucial importance of rapid and accurate diagnosis, as well as appropriate treatment from the perspective of infectious diseases. All of these emergencies demand a high degree of clinical suspicion for accurate diagnosis. Some of them also necessitate the involvement of other medical disciplines, such as neurology in the case of meningitis or surgery for necrotizing fasciitis. Additionally, implementing the right empiric antibiotic regimen or, in the case of malaria, antiparasitic treatment is crucial for improving patient outcomes. As patients with these diagnoses may present at any outpatient department, and efficient and quick management is essential, a deep understanding of diagnostic algorithms and potential pitfalls is of the utmost importance.

Elevated levels of ß2-microglobulin in cerebrospinal fluid in adult patients with viral encephalitis/meningitis.

BACKGROUND: Increased cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) values are attributed to immune activation, lymphoid cell turnover and release of tissue destruction in the central nervous system (CNS). We investigated plasma and CSF ß2-MG levels in adult patients with viral encephalitis/meningitis and their correlations with clinical parameters. METHOD: CSF samples from 26 patients with viral encephalitis/meningitis were collected. Moreover, 24 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 22 enrolled patients and 20 healthy individuals were collected. The ß2-MG levels were measured by immunoturbidimetry on an automatic biochemical analyzer. Clinical data were extracted from an electronic patient documentation system. RESULT: CSF levels of ß2-MG, adenosine deaminase (ADA), white blood cell (WBC), lactate dehydrogenase (LDH), protein and lactate were significantly increased in patients with viral encephalitis/meningitis respectively (p < 0.001, p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.013). In contrast, no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were weakly correlated with WBC (r = 0.426, p = 0.030), lymphocyte percentage (r = 0.599, p = 0.018), ADA (r = 0.545, p = 0.004) and LDH (r = 0.414, p = 0.036), but not with lactate (r = 0.381, p = 0.055), protein (r = 0.179, p = 0.381) and plasma levels of ß2-MG (r = -0.156, p = 0.537) in viral encephalitis/meningitis patients. CONCLUSION: CSF ß2-MG may be a potential inflammatory marker for viral encephalitis/meningitis in adult patients diagnosed with viral encephalitis/meningitis.

Evaluation of pathogen from the FilmArray meningitis/encephalitis panel and recommendations on atypical findings.

BACKGROUND: Infectious meningoencephalitis is a potentially fatal clinical condition that causes inflammation of the central nervous system secondary to the installation of different microorganisms. The FilmArray meningitis/encephalitis panel allows the simultaneous detection of 14 pathogens with results in about one hour. OBJECTIVE: This study is based on retrospectively evaluating the implementation of the FilmArray meningitis/encephalitis panel in a hospital environment, highlighting the general results and, especially, analyzing the consistency of the test results against the clinical and laboratory conditions of the patients. METHODS: Data were collected through the results reported by the BioFire FilmArray system software from the meningitis/encephalitis panel. The correlated laboratory tests used in our analysis, when available, included biochemical, cytological, direct and indirect microbiological tests. RESULTS: In the analyzed period, there were 496 samples with released results. Of the total of 496 samples analyzed, 88 (17.75%) were considered positive, and 90 pathogens were detected, and in 2 of these (2.27%) there was co-detection of pathogens. Viruses were the agents most frequently found within the total number of pathogens detected. Of the 496 proven samples, 20 (4.03%) were repeated, 5 of which were repeated due to invalid results, 6 due to the detection of multiple pathogens and 9 due to disagreement between the panel results and the other laboratory tests and/or divergence of the clinical-epidemiological picture. Of these 20 repeated samples, only 4 of them (20%) maintained the original result after repeating the test, with 16 (80%) being non-reproducible. The main factor related to the disagreement of these 16 samples during retesting was the detection of bacterial agents without any relationship with other laboratory tests or with the patients' clinical condition. CONCLUSION: In our study, simply reproducing tests with atypical results from the FilmArray meningitis/encephalitis panel proved, in most cases, effective and sufficient for interpreting these results.

ANTECEDENTES: A meningoencefalite infecciosa é uma condição clínica potencialmente fatal que causa inflamação do sistema nervoso central secundária à instalação de diversos microrganismos. O painel de meningite/encefalite FilmArray permite a detecção simultânea de 14 patógenos, com resultados em cerca de uma hora. OBJETIVO: Este estudo baseia-se em avaliar retrospectivamente a implementação do painel de meningite/encefalite FilmArray em ambiente hospitalar, destacando os resultados gerais e, principalmente, analisando a consistência dos resultados do teste frente às condições clínicas e laboratoriais dos pacientes. MéTODOS: Os dados foram coletados por meio dos resultados relatados pelo software do sistema BioFire FilmArray do painel de meningite/encefalite. Os exames laboratoriais correlacionados utilizados em nossa análise, quando disponíveis, incluíram exames bioquímicos, citológicos, microbiológicos diretos e indiretos. RESULTADOS: No período analisado, foram 496 amostras com resultados divulgados. Do total de 496 amostras analisadas, 88 (17,75%) foram consideradas positivas e 90 patógenos foram detectados, sendo que em duas destas (2,27%) houve codetecção de patógenos. Os vírus foram os agentes mais frequentemente encontrados dentro do total de patógenos detectados. Das 496 amostras analisadas, 20 (4,03%) foram repetidas, sendo 5 repetidas por resultado inválido, 6 pela detecção de múltiplos patógenos e 9 por discordância dos resultados do painel com os demais exames laboratoriais e/ou divergência do quadro clínico-epidemiológico. Destas 20 amostras repetidas, apenas 4 delas (20%) mantiveram o resultado original após a repetição do teste, sendo 16 (80%) não reprodutíveis. O principal fator relacionado à discordância destas 16 amostras na retestagem foi a detecção de agentes bacterianos sem qualquer relação com os demais exames laboratoriais ou com o quadro clínico dos pacientes. CONCLUSãO: Em nosso estudo, a simples repetição dos testes com resultados atípicos do painel de meningite/encefalite FilmArray mostrou-se, na maior dos casos, efetiva e suficiente para a interpretação destes achados.

Unusual non-infectious cause of meningitis.

Meningitis, though commonly caused by various infectious agents, may also have non-infectious aetiologies. The clinical presentation, however may be identical to infectious meningitis. We present a case of a female in her 50s who presented with fever, headache, vomiting and neck rigidity. She had features of inflammatory polyarthritis, cold sensitivity, puffy digits, alopecia and easy fatigability. No evidence of infection was found, and serological features consistent with mixed connective tissue disease (MCTD) were revealed, which led to the diagnosis of MCTD-related aseptic meningitis.

A multicenter evaluation of the QIAstat-Dx meningitis-encephalitis syndromic test kit as compared to the conventional diagnostic microbiology workflow.

PURPOSE: Rapid diagnosis and treatment of infectious meningitis and encephalitis (ME) is critical to minimize morbidity and mortality. Recently, Qiagen introduced the CE-IVD QIAstat-Dx ME panel (QS-ME) for syndromic diagnostic testing of meningitis and encephalitis. Some data on the performance of the QS-ME in comparison to the BioFire FilmArray ME panel are available. In this study, the performance of the QS-ME is compared to the current diagnostic workflow in two academic medical centers in the Netherlands. METHODS: A total of 110 cerebrospinal fluid samples were retrospectively tested with the QS-ME. The results obtained were compared to the results of laboratory-developed real-time PCR assays (LDTs), IS-pro, bacterial culture, and cryptococcal antigen (CrAg) testing. In addition, the accuracy of the QS-ME was also investigated using an external quality assessment (EQA) panel consisting of ten samples. RESULTS: Four of the 110 samples tested failed to produce a valid QS-ME result. In the remaining 106 samples, the QS-ME detected 53/53 viral targets, 38/40 bacterial targets, and 7/13 Cryptococcus neoformans targets. The discrepant bacterial results consisted of two samples that were previously tested positive for Listeria monocytogenes (CT 35.8) and Streptococcus pneumoniae (CT 40), respectively. The QS-ME detected one additional result, consisting of a varicella-zoster virus signal (CT 35.9), in a sample in which both techniques detected Streptococcus pyogenes. Finally, 100% concordance was achieved in testing a blinded bacterial ME EQA panel. CONCLUSION: The QS-ME is a relevant addition to the syndromic testing landscape to assist in diagnosing infectious ME.

Escherichia coli Meningitis in a 72-year-old Woman.

Spontaneous community-acquired meningitis caused by E. coli is rare in the adult population. It is associated with a high risk of morbidity and mortality. We describe a case of a 72-year-old woman who presented with altered mental status and neck stiffness and was found to have E. coli meningitis. Urine cultures grew E. coli, representing a likely source. The E. coli strain was identified as sequence type 73 (E. coli ST73). Her symptoms and laboratory values improved following antibiotic initiation, and she was discharged from the hospital to a rehabilitation facility.

Evaluation of 17 years of MERIN (Meningitis and Encephalitis register in Lower Saxony, Germany) surveillance system: participants acceptability survey, completeness and timeliness of data.

BACKGROUND: A Meningitis and Encephalitis Surveillance (MERIN) was implemented in 2003 in Lower Saxony, Germany as an alternative to acute flaccid paralyses surveillance, as the latter did not reach WHO sensitivity criteria. The system provides information on circulating enterovirus (EV) serotypes by focussing on patients with suspected aseptic meningitis, encephalitis or acute flaccid paralysis and contributes to the national surveillance in documenting polio free status. MERIN is based on voluntary participation of hospitals. Therefore, our evaluation focusses on acceptability of the system's objectives and performance, and identifying areas for improvement. METHODS: To assess acceptability, 32 contributing hospitals were invited to an online-based survey (11/2021 to 01/2022) to rate the MERIN objectives, laboratory's performance, their workload, modes of processes and communication. Ideas for improvement were collected in open fields. In addition, data completeness and timeliness of laboratory diagnostics were assessed. RESULTS: Of 32 hospitals, 21 responded (66% response rate), sending 30 questionnaires, 25 from pediatric and 5 from neurological departments. High levels of satisfaction with the communication (≥ 96%), timeliness (≥ 81%), and distribution of the results (≥ 85%) were reported, 97% of participants judged the required workload as adequate. The median proportion of eligible patients included in MERIN was 75%. Participants gave rapid and reliable diagnostic testing the highest priority (96%), while monitoring of Germany's polio-free status was rated the lowest (61%). Providing medical reports digitally as well as regular updates about circulating EV serotypes were identified as areas for improvement. Data completeness of selected variables ranged from 78.3 to 99.9%. Median time between sample collection and arrival at laboratory was 2 days [IQR 1-3], EV diagnostics via PCR took one day [IQR 0-6] and EV isolation on cell culture 11 days [IQR 10-13]. CONCLUSION: MERIN is a highly accepted surveillance system. Its quality was enhanced further by addressing the suggested improvements such as regular reports on circulating EV serotypes and facilitating digital access to laboratory results. Our results emphasise the importance of recognizing and considering participants' motivations and expectations, and addressing their priorities, even if this is not the surveillance system's main focus. This approach can be applied to surveillance systems of other non-mandatory notifiable diseases.

C-reactive protein concentration has limited value in the diagnosis of meningoencephalitis of unknown origin in dogs.

OBJECTIVES: To evaluate blood and cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP) in dogs with meningoencephalitis of unknown origin (MUO); to evaluate whether blood CRP concentration is associated with epidemiological, clinicopathologic, and MRI findings; and to investigate blood CRP predictive power in survival. ANIMALS: 30 client-owned dogs with MUO, 15 client-owned dogs with steroid-responsive meningitis arteritis (SRMA; positive control group), and 15 healthy dogs (negative control group). METHODS: Blood CRP concentration was measured in each group, while it was performed in CSF only in the MUO and SRMA groups. The analysis of epidemiological data included breed, age, sex, duration of clinical signs, and history of seizures. Blinded analysis of MRI was performed based on a classification grid, and traditional CSF analysis parameters were assessed. The predictive power of blood CRP concentration regarding survival at 6 months was investigated. RESULTS: Of the 30 dogs with MUO, 9 (30%) had an increased CRP concentration in blood, and 3 (10%) showed a measurable CRP in CSF. Median blood CRP concentration in dogs with MUO was 0.1 mg/L (range, 0.1 to 102 mg/L), which was not statistically different from the healthy dog group but significantly lower than the SRMA control group. Only the duration of clinical signs was positively associated with an increased blood CRP level. Blood CRP concentration was not associated with survival at 6 months. CLINICAL RELEVANCE: Blood CRP concentration is of limited value for the diagnosis and prognosis of dogs with MUO. Chronicity of the disease may be associated with an increased concentration of blood CRP.