Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review.

OBJECTIVES: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.

Clinical Observation of Various Types of Idiopathic Hypertrophic Cranial Pachymeningitis.

BACKGROUND: To assist doctors in making better treatment decisions and improve patient prognosis, it is important to determine which therapy modalities are suitable for various forms of idiopathic hypertrophic cranial pachymeningitis (IHCP). METHODS: All cases were received from the hospital medical record system, and some follow-up information was gathered through telephone follow-up. RESULTS: A total of 26 patients, 14 men and 12 women, with ages ranging from 20 to 73 years and a mean of 47.42 years, were included in the research. Regular types were less likely to recur than irregular and nodular types, focal types were less likely to recur than diffuse types, and corticosteroid-refractory types were more likely to recur than corticosteroid-sensitive types. CONCLUSIONS: The extent and shape of the lesion and susceptibility to corticosteroids are potential factors that could influence recurrence. Futhermore, this paper also proposes the fibroblasts as a new therapeutic target which may improve the quality of prognostic survival of patients.

IgG4-Related Spinal Hypertrophic Pachymeningitis With Neurological Deficit: A Report of 2 Cases.

CASE: Immunoglobulin G4 (IgG4)-related spinal hypertrophic pachymeningitis (IgG4-RHP) is a rare disease characterized by diffuse inflammatory fibrosis of the spinal dura mater that can cause myelopathy and neurological deficits. Here, we report 2 cases in which both patients presented with myelopathy and paraplegia. They underwent decompressive laminectomy, and the diagnoses were confirmed through histopathologic examination. Both patients received prednisolone postoperatively, which was subsequently switched to methotrexate for maintenance. CONCLUSION: Two cases of IgG4-RHP were successfully treated with decompressive laminectomy and combined therapy with steroids and other immunosuppressive agents.

Hippocampal Metabolic Alterations and Cognitive Dysfunction in Varicella Zoster Virus Meningitis: A Single-Center Case Series Study.

BACKGROUND Meningitis has been found to be associated with dementia. Different pathogens of meningitis lead to different cognitive impairments. However, the change of cognitive function and cellular metabolism in the hippocampus in varicella zoster virus (VZV) meningitis has received little attention. We aimed to explore the cognitive function and changes of cellular metabolism in bilateral hippocampal regions in VZV meningitis. MATERIAL AND METHODS We used magnetic resonance spectroscopy to check the cellular metabolism in the bilateral hippocampal region in 23 VZV meningitis patients and 19 controls in our hospital from June 2020 to November 2022. Also, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and the correlation between MoCA scores and cellular metabolism in the bilateral hippocampal region was analyzed. RESULTS Six (26.1%) of the 23 patients with VZV meningitis had cognitive decline. Compared with that of the control group, the MoCA scores of VZV meningitis patients was much impaired (25.88±2.31 vs 27.74±1.94, P<0.05), visual-spatial executive function and delayed recall were significantly decreased (P<0.05), and N-acetylaspartate (NAA)/creatine (Cr) ratios in the bilateral hippocampus of patients with VZV meningitis were significantly lower (P<0.05). NAA/Cr ratios in the left and right hippocampus were positively correlated with MoCA scores (r=0.4158, P=0.0385; r=0.5274, P=0.0010, respectively), and negatively correlated with white blood cell count (P<0.01) and protein content in cerebrospinal fluid (P<0.05). CONCLUSIONS Patients with VZV meningitis had cognitive dysfunction and altered cellular metabolism of bilateral hippocampal regions. The main cognitive abnormalities were visual-spatial executive function and delayed recall.

Meningitis associated with HHV-7 in an Iranian immunocompetent adolescent girl.

There is limited literature regarding meningitis associated with HHV-7. This article reports an immunocompetent adolescent girl who developed fever, headache, and meningism which CSF molecular analysis with PCR was positive only for HHV-7. Interestingly, persistent cavum septum pellucidum and cavum vergae were observed on brain magnetic resonance imaging. The patient received antibiotics, dexamethasone, and acyclovir and then she gained full recovery. HHV-7 is a rare and yet possible pathogen in patients with meningitis, and this is the first described case report from Iran.

Off-label use of eculizumab for neurological symptoms and progressive vision loss.

We describe the results of eculizumab treatment of a patient with pachymeningitis, inflammatory infiltration of the left frontal lobe, and cerebral hematoma, who presented with progressive vision loss, epileptic seizures, and abnormal pattern of the complement system parameters. A 30-year-old female patient, initially diagnosed with hypereosinophilia and a tumour of the left orbit, developed a significant visual impairment in the left eye, progressive vision loss in the right eye, and neurological symptoms in the form of epileptic seizures and behavioural changes. Magnetic resonance imaging (MRI) revealed thickening of the dura mater in the left frontal area, slight oedema of the cortex, and subcortical white matter. Orbit biopsy showed non-specific inflammatory infiltrates. Despite the initial good response, symptoms progressed during treatment with glucocorticoids and immunosuppressants. Increased activity of the alternative complement pathway accompanied by a low level of its main inhibitor, factor H (FH), and the presence of anti-FH autoantibodies, was found. Genetic analysis revealed several missense variants of complement proteins, including two disease-linked mutations in FH (p.H402Y) and FI (T300A). An attempt to apply a complement C5 blocker, eculizumab, has been made. Neurological symptoms subsided, vision loss was inhibited, laboratory parameters improved, and discontinuation of steroid therapy was possible. The case underlines the role of complement system dysregulation in neurological distress.

A case of Lymphoplasmacyte-rich meningioma mimicking pachymeningitis.

BACKGROUND: Lymphoplasmacyte-rich meningioma (LPRM) is a rare form of meningioma characterized by prominent lymphoplasmacytic infiltrates into the tumor. Report of flat growth of LPRM mimicking pachymeningitis is rare in the literature. CASE PRESENTATION: A 55-year-old female who suffered from episodes of headache and seizures has been diagnosed with pachymeningitis for 4 years because post contrast brain MRI demonstrated enhanced carpet-like dura lesion in the left frontal lobe. The lesion kept unchanged on yearly follow-ups until a recent brain MRI found the lesion grew significantly into a mass. The lesion was resected and pathology suggested LPRM. CONCLUSION: LPRM may present as carpet-like growth pattern on MRI. Long-term follow-up in patients with pachymeningitis is necessary.

Recurrent IgG4-Related Meningeal Disease of the Cervicothoracic Spine: A Case Report and Review of the Literature.

Background: IgG4-related disease is a rare, recently recognized chronic inflammatory disease. IgG4-related hypertrophic pachymeningitis (IgG4-RHP) of the central nervous system predominantly involves the cranial meninges. Spinal involvement remains rare. Objective: We report a case of recurrent cervicothoracic IgG4-RHP and review the surgical literature. Methods and Materials: A 35-year-old woman presented with a 6-month history of neck and right shoulder pain, progressive right triceps weakness and paresthesias in the right C8 and T1 dermatomes. MRI demonstrated a T2 hypointense epidural soft tissue mass extending from C6-T1. The patient underwent C6-T1 laminoforaminotomy and partial resection with near complete symptom resolution. Histopathology was consistent with diagnosis of IgG4-RHP. Eighteen months postoperatively, she experienced symptom recurrence necessitating re-operation and adjuvant postoperative prednisone with complete resolution at 40-months' follow-up. Results and Conclusions: Of the now nineteen confirmed cases of IgG4-RHP, fifteen underwent surgery. A majority achieved partial resection. Three surgical patients did not receive adjuvant therapy with symptomatic recurrence between 2 and 18 months.

A case of idiopathic hypertrophic pachymeningitis with high adenosine deaminase in cerebrospinal fluid.

Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) has been reported as useful to diagnose tuberculous meningitis and hypertrophic pachymeningitis (HP). The case of a 59-year-old woman with impaired vision and an auditory disturbance due to massive intracranial HP is presented. Although acid-fast bacillus cultures and polymerase chain reaction tests for Mycobacterium tuberculosis in the CSF were negative, tuberculous HP was diagnosed clinically because of the high ADA in CSF, and anti-tuberculosis drugs were administered with prednisolone because idiopathic HP (IHP) could not be ruled out. Since the impaired vision worsened with prednisolone reduction despite the continuation of anti-tuberculosis drugs, a dural biopsy was performed, and the patient was diagnosed with IHP. ADA is associated with lymphocyte proliferation and differentiation and increased by activation of cell-mediated immunity. Elevated CSF-ADA might be caused by lymphocyte infiltration in the thickened dura mater.

Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood-brain barrier.

The neurovascular unit, which consists of vascular cells surrounded by astrocytic end-feet and neurons, controls cerebral blood flow and the permeability of the blood-brain barrier (BBB) to maintain homeostasis in the neuronal milieu. Studying how some pathogens and drugs can penetrate the human BBB and disrupt neuronal homeostasis requires in vitro microphysiological models of the neurovascular unit. Here we show that the neurotropism of Cryptococcus neoformans-the most common pathogen causing fungal meningitis-and its ability to penetrate the BBB can be modelled by the co-culture of human neural stem cells, brain microvascular endothelial cells and brain vascular pericytes in a human-neurovascular-unit-on-a-chip maintained by a stepwise gravity-driven unidirectional flow and recapitulating the structural and functional features of the BBB. We found that the pathogen forms clusters of cells that penetrate the BBB without altering tight junctions, suggesting a transcytosis-mediated mechanism. The neurovascular-unit-on-a-chip may facilitate the study of the mechanisms of brain infection by pathogens, and the development of drugs for a range of brain diseases.

Google search behavior for meningitis and its vaccines: an infodemiological study.

BACKGROUND: The internet has made significant contributions towards health education. Analyzing the pattern of online behavior regarding meningitis and vaccinations may be worthwhile. It is hypothesized that the online search patterns in meningitis are correlated with its number of cases and the search patterns of its related vaccines. METHODS: This was an infodemiological study that determined the relationship among online search interest in meningitis, its worldwide number of cases and its associated vaccines. Using Google Trends™ Search Volume Indices (SVIs), we evaluated the search queries "meningitis," "pneumococcal vaccine," "BCG vaccine," "meningococcal vaccine" and "influenza vaccine" in January 2021, covering January 2008 to December 2020. Spearman rank correlation was used to determine correlations between these queries. RESULTS: The worldwide search interest in meningitis from 2008 to 2020 showed an average SVI of 46 ± 8.8. The most searched topics were symptoms, vaccines, and infectious agents with SVIs of 100, 52, and 39, respectively. The top three countries with the highest search interest were Ghana, Kazakhstan, and Kenya. There were weak, but statistically significant correlations between meningitis and the BCG (ρ = 0.369, p < 0.001) and meningococcal (ρ = 0.183, p < 0.05) vaccines. There were no statistically significant associations between the number of cases, influenza vaccine, and pneumococcal vaccine. CONCLUSION: The relationships among the Google SVIs for meningitis and its related vaccines and number of cases data were inconsistent and remained unclear. Future infodemiological studies may expand their scopes to social media, semantics, and big data for more robust conclusions.

Promotion properties of TLR7 in pediatric meningitis via the NF-κB pathway.

Meningitis outcome is associated with the severity of inflammation in the subarachnoid space and that the outcome can be improved through anti-inflammation. However, a comprehensive understanding of the molecular basis underlying inflammatory responses in meningitis remains enigmatic. In the current study, we sought to determine the molecular mechanism of TLR7/NF-κB on the development of meningitis in children. Cerebrospinal fluid of patients with meningitis and children with simple febrile convulsions was collected, and meningitis mouse model was induced. TLR7 expression was determined in the serum of meningitis model mice and the cerebrospinal fluid of patients using RT-qPCR and Western blot. Afterwards, loss- and gain- function assays were conducted to determine the functional role of TLR7 in meningitis mouse model. The level of procalcitonin (PCT) and the number of bacterial colonies in the serum were analyzed. ELISA was used to detect the expression of inflammatory factors. Upregulated level of TLR7 was observed in patients and mice with meningitis. Inhibiting the expression of TLR7 inhibited the development of meningitis. Overexpressing TLR7 can activate the NF-κB signaling pathway and promote mouse meningitis. NF-κB signaling pathway inhibitor reversed promotion of meningitis caused by TLR7 activation. Our study provides evidence that TLR7 elevation can activate the NF-κB signaling pathway and promote meningitis in mice.

Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis.

Streptococcus suis serotype 2 is a crucial pathogenic cause of bacterial meningitis, a life-threatening disease with neurological sequelae and high rates of mortality. Inflammation triggered by S. suis infection must be precisely regulated to prevent further tissue damage. As a glucocorticoid anti-inflammatory mediator, annexin A1 (AnxA1) mainly acts through formyl peptide receptor 2 (Fpr2) to alleviate inflammation in the peripheral system. In this study, we evaluated the roles of AnxA1 and Fpr2 in a mouse model of S. suis meningitis created via intracisternal infection in Fpr2-deficient (Fpr2-/-) and wild-type (WT) mice. We revealed that Fpr2-/- mice were highly susceptible to S. suis meningitis, displaying increased inflammatory cytokine levels, bacterial dissemination, and neutrophil migration compared with WT mice. Additionally, AnxA1 exerted anti-inflammatory effects through Fpr2, such as attenuation of leukocyte infiltration, inflammatory mediator production, and astrocyte or microglial activation in the brain. Importantly, we found that the antimigratory function of AnxA1 decreases neutrophil adherence to the endothelium through Fpr2. Finally, an in vitro study revealed that AnxA1 potentially suppresses interleukin-6 (IL-6) expression through the Fpr2/p38/COX-2 pathway. These data demonstrated that Fpr2 is an anti-inflammatory receptor that regulates neutrophil migration in mice with S. suis meningitis and identified AnxA1 as a potential therapeutic option.

Case Report: Chronic Fungal Meningitis Masquerading as Tubercular Meningitis.

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of Fonsecaea pedrosoi, which is classically known to cause brain abscesses. Here, we report the diagnostic odyssey in a patient with chronic meningitis from a region endemic for tuberculosis and describe the challenges in establishing the accurate diagnosis. Lack of therapeutic response to an adequate trial of empirical antitubercular therapy warrants search for alternative causes, including fungal meningitis. We highlight the uncommon manifestation of F. pedrosoi with chronic meningitis as well as the protracted clinical course despite not receiving antifungal therapy.

The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease.

Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Galα1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes PN and PO We show here that subtype PN is distributed in the systemic strains causing meningitis, whereas type PO is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype PN strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type PN SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type PO SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type PN SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.

Immunoglobulin G4-Related Hypertrophic Pachymeningitis of the Spine: A Case Report and Systematic Review of the Literature.

BACKGROUND: Spinal immunoglobulin G4-related hypertrophic pachymeningitis (IgG4-HP) is a rare disease. Little information is known regarding the diagnosis, management, and prognosis of patients with spinal IgG4-HP. METHODS: The authors present a case of spinal IgG4-HP with a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies (up to April 2020) that reported patients with spinal IgG4-HP, based on the criteria of Japan College of Rheumatology, were identified from the PubMed and Cochrane Library databases. RESULTS: This systematic review identified 33 patients, including the present case, of whom 21 were male and 12 were female. The mean value of age was 51.2 (±12.6) years. Eight patients had systemic involvement. In addition, among 33 patients, 13 patients had an elevated serum IgG4. Surgery was performed in 31 patients. Steroid therapy alone and steroid therapy with immunosuppressants were effective in 94% and 100% of the cases, respectively. Furthermore, 31 of 33 patients reported improved outcomes, 1 patient died due to infection, and in 2 patients the data were not available. CONCLUSIONS: Spinal IgG4-HP is a rare entity. In addition, it should be considered in the differential diagnosis of space-occupying lesions around the spinal cord. Histopathology with immunohistochemistry results provides the most reliable evidence for diagnosis. Steroid therapy is the first line of treatment. Surgical decompression may be required in patients presenting with nerve root and/or spinal cord compression. Long-term follow-up is necessary for patients with spinal IgG4-HP.

Reintroduction of immune-checkpoint inhibitors after immune-related meningitis: a case series of melanoma patients.

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen-4 and programmed cell death ligand-1) are associated with several immune-related neurological disorders. Cases of meningitis related to ICIs are poorly described in literature and probably underestimated. Several guidelines are available for the acute management of these adverse events, but the safety of resuming ICIs in these patients remains unclear. We conducted a retrospective case series of immune-related meningitis associated with ICIs that occurred between October 1 2015 and October 31 2019 in two centers: Saint-Louis and Cochin hospitals, Paris, France. Diagnosis was defined by a (1) high count of lymphocytes (>8 cells/mm3) and/or high level of proteins (>0.45 g/L) without bacteria/virus or tumor cells detection, in cerebrospinal fluid and (2) normal brain and spine imaging. Patients were followed-up for at least 6 months from the meningitis onset. Seven cases of immune-related meningitis are here reported. Median delay of meningitis occurrence after ICIs onset was 9 days. Steroid treatment was introduced in four patients at a dose of 1 mg/kg (prednisone), allowing a complete recovery within 2 weeks. The other three patients spontaneously improved within 3 weeks. Given the favorable outcome, ICIs were reintroduced in all patients. The rechallenge was well tolerated and no patients experienced meningitis recurrence. In conclusion, in our series, the clinical course was favorable and steroids were not always required. Resuming ICIs in these patients appeared safe and can thus be considered in case of isolated meningitis. However, a careful analysis of the risk/benefit ratio should be done on a case-by-case basis.