Advances in the pathogenesis and treatment of pneumococcal meningitis.

Streptococcus pneumoniae is a common pathogen associated with community-acquired bacterial meningitis, characterized by high morbidity and mortality rates. While vaccination reduces the incidence of meningitis, many survivors experience severe brain damage and corresponding sequelae. The pathogenesis of pneumococcal meningitis has not been fully elucidated. Currently, meningitis requires bacterial disruption of the blood - brain barrier, a process that involves the interaction of bacterial surface components with host cells and various inflammatory responses. This review delineates the global prevalence, pathogenesis, and treatment strategies of pneumococcal meningitis. The objective is to enhance the thorough comprehension of the clinical manifestations and biological mechanisms of the disease, thereby enabling more efficient prevention, diagnosis, and therapeutic interventions.

Austrian syndrome: Report of one case and a systematic review of case reports - new insights.

OBJECTIVE: The objective of this review was to gain new insight into the rare condition, Austrian syndrome: the triad of endocarditis, meningitis and pneumonia caused by Streptococcus pneumoniae. METHODS: A systematic review of case reports was conducted using the PRISMA guideline. Cases were rigorously screened to meet a set of well-defined inclusion criteria. Relevant data was aggregated and reported using descriptive statistics. RESULTS: Seventy-one cases from 69 case reports were included in the final review. The mean age was 56.5 years with a male-to-female ratio of 2.4:1. Alcoholism was reported in 41% of patients. Altered mental state (69%) and fever (65%) (mean temperature on admission = 38.9°C) were the commonest presenting symptoms. The mean duration of symptoms before presentation to the hospital was 8 days. The aortic valve was most commonly affected (56%). The mean duration of antibiotic therapy was 5.6 weeks. Seventy percent of patients were admitted to the intensive care unit (ICU). Fifty-six percent of patients had valvular surgery. The average length of stay in the hospital was 36.9 days. Mortality was recorded in 28% of patients. CONCLUSION: Austrian syndrome is rare but deadly. The true incidence is unknown but is commoner in middle-aged men and in alcoholics. Affected patients are usually critically unwell, often requiring ICU admission and prolonged hospital stays. Treatment is aggressive including prolonged courses of antibiotics and often, surgery. Despite these, the case fatality rate is high, with death occurring in over a quarter of patients. Surgery appears to be associated with better prognosis.

A Retrospective Study of Recurrent Bacterial Meningitis in Children: Etiology, Clinical Course, and Treatment.

Objectives: Recurrent bacterial meningitis (RBM) is a rare but life-threatening disease. This study aims to analyze the clinical features, potential causes, and therapeutic outcomes of RBM in children. Methods: This article retrospectively reviews the clinical characteristics, etiologies, and treatments in children with RBM hospitalized in Hebei children's hospital from 2012 to 2020. Results: A total of 10 children with RBM, five males and five females, were included in this study. The age of RBM in children spans from the neonatal stage to the childhood stage. The underlying illnesses were identified and classified as cerebrospinal fluid rhinorrhea (1 case), humoral immunodeficiency with Mondini dysplasia (1 case), common cavity deformity with cerebrospinal fluid ear leakage (1 case), Mondini malformations (2 cases), incomplete cochlear separation type I with a vestibular enlargement (2 cases), local inflammation of the sphenoid bone caused by cellulitis (1 case), congenital skull base defects (1 case), and congenital dermal sinus with intraspinal abscess (1 case). 6 patients chose targeted therapy for potential reasons. Conclusions: Congenital abnormalities or acquired injuries lead to intracranial communication with the outside world, which can quickly become a portal for bacterial invasion of the central nervous system, resulting in repeated infections.

Repetitive transcranial magnetic stimulation activates glial cells and inhibits neurogenesis after pneumococcal meningitis.

Pneumococcal meningitis (PM) causes damage to the hippocampus, a brain structure critically involved in learning and memory. Hippocampal injury-which compromises neurofunctional outcome-occurs as apoptosis of progenitor cells and immature neurons of the hippocampal dentate granule cell layer thereby impairing the regenerative capacity of the hippocampal stem cell niche. Repetitive transcranial magnetic stimulation (rTMS) harbours the potential to modulate the proliferative activity of this neuronal stem cell niche. In this study, specific rTMS protocols-namely continuous and intermittent theta burst stimulation (cTBS and iTBS)-were applied on infant rats microbiologically cured from PM by five days of antibiotic treatment. Following two days of exposure to TBS, differential gene expression was analysed by whole transcriptome analysis using RNAseq. cTBS provoked a prominent effect in inducing differential gene expression in the cortex and the hippocampus, whereas iTBS only affect gene expression in the cortex. TBS induced polarisation of microglia and astrocytes towards an inflammatory phenotype, while reducing neurogenesis, neuroplasticity and regeneration. cTBS was further found to induce the release of pro-inflammatory cytokines in vitro. We conclude that cTBS intensified neuroinflammation after PM, which translated into increased release of pro-inflammatory mediators thereby inhibiting neuroregeneration.

MeningiSSS: A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis.

BACKGROUND: Knowing the individual child's risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors. METHODS: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure. RESULTS: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores' results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson-Todd Scale (AUC = 0.79) was all associated with death. CONCLUSIONS: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.

Dorsal subscapularis approach for the surgical drainage of subscapularis intramuscular abscess: a case report.

BACKGROUND: Abscess formation in the subscapularis muscle is a rare clinical condition. Few reports are available regarding the treatment methods and surgical approaches for subscapularis intramuscular abscesses. Here, we describe a case of subscapularis intramuscular abscess that was treated successfully via surgical drainage using a new approach, the "dorsal subscapularis approach". CASE PRESENTATION: A 67-year-old woman presented to our hospital with complaints of fever and disturbance of consciousness. Two days prior to visiting our hospital, right shoulder pain and limited range of motion in the shoulder were noted. Cerebrospinal fluid examination and contrast-enhanced computed tomography (CT) imaging on admission revealed a right subscapularis intramuscular abscess with concomitant bacterial meningitis. The patient's clinical symptoms improved after antibiotic administration for 3 weeks, but the right shoulder pain persisted. Contrast-enhanced CT imaging performed after antibiotic administration revealed an abscess in the right shoulder joint space, in addition to a capsule of the abscess in the right subscapularis muscle. We performed open surgical drainage for the abscess, which had spread from the subscapularis muscle to the glenohumeral joint. Using the deltoid-pectoral approach, we detected exudate and infected granulation tissue in the joint cavity. Furthermore, we separated the dorsal side of the subscapularis muscle from the scapula using a raspatory and detected infected granulation tissue in the subscapularis muscle belly. We performed curettage and washed as much as possible. After surgery, antibiotic administration continued for 2 weeks. The patient's right shoulder pain subsided and CT performed 2 months after surgery revealed no recurrence of infection. CONCLUSIONS: The present case indicated that a subscapularis intramuscular abscess could lead to severe concomitant infections of other organs via the hematogenous route. Thus, early detection and treatment are necessary. Moreover, in this case, surgical drainage using a dorsal subscapularis approach was beneficial to treating the abscess, which had spread from the subscapularis muscle to the glenohumeral joint.

[Extra-ventricular drainage for the treatment of pneumococcal meningitis and hydrocephalus: a case report].

A 53-year-old man was referred to our hospital because of fever and disturbed consciousness with a left-sided toothache from 5 days ago. Neurological examinations revealed a low level of consciousness, nuchal rigidity, bilateral mydriasis, and positive Babinski sign. A lumbar puncture yielded clouded fluid with a WBC 22,698/µl (polynuclear cell 98%), 681 mg/dl of protein and 0 mg/dl of glucose. The antigen of Streptococcus pneumoniae in urine and cerebrospinal fluid (CSF) were positive. Streptococcus pneumoniae was isolated from CSF culture. Brain CT on admission showed a communicating hydrocephalus. Diagnosis of pneumococcal meningitis with hydrocephalus was made and we treated with ceftriaxone and dexamethasone. The lumbar drainage placed at L 3/4 level became occluded, thus, extra-ventricular drainage was performed. Intracranial pressure (ICP) was 20 cmH2O upon insertion of the ICP sensor. At Day 2, the ICP decreased to 10 cmH2O and never increased during his course of hospitalization. Repeat brain CT showed no hydrocephalus. He responded to antimicrobial therapy and became lucid and afebrile. At Day 4, the extra-ventricular drainage was removed because of bleeding from right choroid plexus on brain CT. We treated with antimicrobial therapy until Day 21. He was transferred to another hospital for rehabilitation with mild neurological sequelae at Day 31. The cases presenting with hydrocephalus in the acute phase of bacterial meningitis has a high mortality rate. The presence of hydrocephalus is a poor prognostic factor. Although the therapeutic value of extra-ventricular drainage for hydrocephalus has been unclear, his report represents a case for neurologists to consider performing extra-ventricular drainage for hydrocephalus.

Hospital cost of invasive pneumococcal disease in children aged under 15 years old in Tunisia.

BACKGROUND: Pneumococcal infections are an important cause of morbidity and mortality in the world and in Tunisia. Data on the economic burden of these infections are needed to inform decision-making to include pneumococcal vaccinations in routine childhood immunization. AIMS: This study aimed to estimate the medical cost of hospitalizations due to invasive pneumococcal disease (pneumonia and meningitis) among children aged under 15 years old in Tunisia. METHODS: A prospective multicentre study was conducted in 15 paediatric departments, across different socio-economic areas of Tunisia, from June 2014 to May 2015. All children aged under 15 years old who were hospitalized for pneumococcal pneumonia or confirmed bacterial meningitis were enrolled. A case report form was completed for every eligible case. Activity Based Costing method was used to estimate the hospital cost. Data entry and statistical analysis were conducted using SPSS, version 20.0. RESULTS: During the study period, 727 children were hospitalized for pneumococcal pneumonia and 60 children were hospitalized for bacterial meningitis, among them 21(35%) had confirmed pneumococcal meningitis. The median hospital cost for pneumococcal pneumonia was 353.910 Tunisian Dinars (TND) and TND 1680.632 for pneumococcal meningitis. Using overall data extrapolation, it was estimated that nearly 1091 hospitalizations for pneumococcal pneumonia and 69 hospitalizations for pneumococcal meningitis occurred each year in Tunisian children aged under 15 years of age, incurring total costs of TND 502 079.408. CONCLUSION: The economic burden of pneumococcal infections seems to be substantial in Tunisia. The estimated costs does not reflect the real costs of this infection. Cost-effectiveness studies would be helpful to inform policy-makers to take appropriate decisions.

Transcranial Doppler in pediatric emergency and intensive care unit: a case series and literature review.

PURPOSE: Transcranial Doppler (TCD) has been used for more than 30 years in clinical practice. Although adult intensive care is relatively well covered, pediatric cases are still underrepresented. We intend to review a series of pediatric cases where TCD was determinant in clinical decisions and a literature review on this topic. METHODS: We describe cases with different pathologies where TCD had an important role in clinical management of the patients. We discuss TCD utility and potential role both in the emergency department and the intensive care unit. RESULTS: Five patients with different neurologic insults are presented. TCD was useful in the identification of intracranial hypertension in traumatic brain injury, hydrocephalus and central nervous system infection; identification of decreased cerebral perfusion pressure in hypovolemic shock and the diagnosis of impending cerebral circulatory arrest in a child with meningococcal septicemia. We discuss how TCD can be used in emergency and intensive care settings, reviewing relevant literature and our own experience. CONCLUSIONS: Non-invasive testing using TCD can aid clinical decisions. More widespread use of this technique will allow for better care of children with neurologic insults.

Cystic Encephalomalacia following Vasculopathy and Vasospasm of Proximal Intracranial Arteries Due to Pneumococcal Meningitis in a Infant.

Despite the availability of modern antibiotics, pneumococcal meningitis in both children and adults remains a severe disease-one known to frequently cause grave complications and residual disability. Although the appearance of arterial vasospasms in bacterial meningitis systematically has been investigated and reported on for adult patients, such research is lacking when it comes to infants. We report on a 4-week-old infant who, 6 days after onset of pneumococcal meningitis, suffered severe neurological deterioration with treatment-resistant seizures and coma. Generalized cortical and subcortical edema developed in conjunction with diminished cerebral blood flow, as depicted in magnetic resonance angiography and serial Doppler-sonographic examinations. The ischemia resulted in extensive cystic encephalomalacia. We propose that the degree of variation in cerebral blood flow in the acute phase was the result of an extensive arterial vasculopathy involving vasospasms. Awareness of this complication and prospective serial Doppler-sonographic examinations may improve our understanding of the connection between brain edema and vasculopathy. At present, however, no effective treatment appears available.

Pediatric Acute Otitis Media in the Era of Pneumococcal Vaccination.

Objectives (1) Describe longitudinal trends in annual prevalence of hospital admission for pediatric acute otitis media (AOM) and complications of AOM (CAOM) since introduction of pneumococcal vaccination in 2000 and (2) describe the longitudinal trend of prevalence of hospital admission for pneumococcal meningitis in children with AOM-related diagnoses in the postvaccination era. Study Design Retrospective analysis of Kids' Inpatient Database from 2000 to 2012. Setting Community, nonrehabilitation hospitals. Subjects and Methods To determine annual prevalence of admission for AOM/CAOM, nationally weighted frequencies of children aged <21 years with acute suppurative otitis media, acute mastoiditis, suppurative labyrinthitis, and/or acute petrositis were collected. The frequency of coexisting pneumococcal meningitis diagnoses among these patients was also collected. Trend analysis of prevalences of admission for AOM/CAOM and for pneumococcal meningitis occurring in the setting of AOM/CAOM from 2000 to 2012 was performed. Results Between 2000 and 2012, annual prevalence of admission for AOM/CAOM decreased from 3.956 to 2.618 per 100,000 persons ( P < .0001) (relative risk reduction 34%). Declines in admission prevalence were most pronounced in children <1 year of age (from 22.647 to 8.715 per 100,000 persons between 2000 and 2012, P < .0001) and 1 to 2 years of age (from 13.652 to 5.554 per 100,000 persons between 2000 and 2012, P < .0001). For all ages, the admission prevalence for pneumococcal meningitis and concomitant AOM/CAOM decreased (from 1.760 to 0.717 per 1,000,000 persons, P < .0001) over the study period. Conclusions The prevalence of hospital admission for pediatric AOM/CAOM has declined since the advent of pneumococcal vaccination. Admission rates for pneumococcal meningitis with AOM/CAOM have similarly declined.

Hydrotherapy for the long-term ventilated patient: A case study and implications for practice.

Hydrotherapy of mechanically ventilated patients has been shown to be safe and feasible in both the acute stages of critical illness and in those requiring long term mechanical ventilation. This case study describes the hydrotherapy sessions of a 36 year old female, who after suffering complications of pneumococcal meningitis, became an incomplete quadriplegic and required long term mechanical ventilation. When implementing hydrotherapy with patients on mechanical ventilation a number of factors should be considered. These include staff resources and training, airway and ventilation management, patient preparation and safety procedures. Hydrotherapy can be safely utilised with mechanically ventilated patients, and may facilitate a patient's ability to participate in active exercise and rehabilitation.

Therapeutic hypothermia and inhalation anesthesia in a patient with severe pneumococcal meningitis and secondary cardiac arrest.

Therapeutic hypothermia was associated with increased mortality in patients with severe bacterial meningitis in a large randomized trial. It still remains a treatment strategy for comatose survivors of cardiac arrest. There are several potential advantages of inhalational anesthetics as long-term sedation agents compared to intravenous sedation, however, uncontrollable increases of intracranial pressure were observed in neurocritical patients. Here we present a patient with severe bacterial meningitis and secondary cardiac arrest where therapeutic hypothermia and inhalational anesthesia were successfully used. A 59-year old female with a history of a vestibular Schwannoma surgery on the left side was admitted with signs of meningitis. Within minutes after admission, she further deteriorated with respiratory arrest, followed by cardiac arrest. She remained comatose after return of spontaneous circulation. The standard treatment of severe meningitis (steroids, antibiotics, insertion of intracranial pressure probe and external ventricular drainage) along with therapeutic hypothermia and inhalational anesthesia were implemented. Intracranial pressure remained stable and daily neurological examination was possible without being confounded by concurrent sedation. She was discharged home without neurological sequelae after 27days. In selected patients with meningitis, therapeutic hypothermia may still present a treatment option, and the long-term use of inhalational anesthetics could be appropriate with concomitant intracranial pressure monitoring.

Clinical findings and management of patients with meningitis with an emphasis on Haemophilus influenzae meningitis in rural Tanzania.

INTRODUCTION: The spectrum of meningitis pathogens differs depending on the age of patients and the geographic region, amongst other. Although meningitis vaccination programs have led to the reduction of incidence rates, an imbalance between low- and high-income countries still exists. METHODS: In a hospital-based study in rural northern Tanzania, we consecutively recruited patients with confirmed meningitis and described their clinical and laboratory characteristics. RESULTS: A total of 136 patients with meningitis were included. Fever (85%), meningism (63%) and impairment of consciousness (33%) were the most frequent clinical symptoms/signs. Nearly 10% of all patients tested were positive for malaria. The majority of the patients with bacterial meningitis (39%), especially those under 5years of age, were confirmed to be infected with Haemophilus influenzae (26%), Streptococcus pneumoniae (19%) and Neisseria meningitidis (15%). Haemophilus influenzae represented the dominant causative organism in children under 2years of age. CONCLUSION: Our study emphasizes the importance of recognizing warning symptoms like fever, meningism and impairment of consciousness, implementing laboratory tests to determine responsible pathogens and evaluating differential diagnoses in patients with meningitis in sub-Saharan Africa. It also shows that Haemophilus influenza meningitis is still an important cause for meningitis in the young, most probabaly due to lack of appropriate vaccination coverage.

V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Here, we have performed a prospective nationwide genetic association study using the Human Exome BeadChip and identified gene variants in encoding dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V-akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis. No clinical replication cohort is available, so we validated the role of one of these targets, AKT3, in a pneumococcal meningitis mouse model. Akt3 deficient mice had worse survival and increased histopathology scores for parenchymal damage (infiltration) and vascular infiltration (large meningeal artery inflammation) but similar bacterial loads, cytokine responses, compared to wild-type mice. We found no differences in cerebrospinal fluid cytokine levels between patients with risk or non-risk alleles. Patients with the risk genotype (rs10157763, AA) presented with low scores on the Glasgow Coma Scale and high rate of epileptic seizures. Thus, our results show that AKT3 influences outcome of pneumococcal meningitis.

Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path).

Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path).