Pneumococcal Meningitis Induces Hearing Loss and Cochlear Ossification Modulated by Chemokine Receptors CX3CR1 and CCR2.

PURPOSE: Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice. METHODS: We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 105 colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function. RESULTS: Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4 days of infection, and neo-ossification by 14 days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3 days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2 weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis. CONCLUSIONS: Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2 weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is robust and can affect all three scalae. Our results suggest that CCR2 may assist in controlling infection and maintaining cochlear patency, as CCR2 knockout mice experienced more severe disease, more rapid hearing loss, and more advanced cochlear ossification after pneumococcal meningitis. CX3CR1 also may play an important role in the maintenance of cochlear patency.

Combining antibiotic with anti-TLR2/TLR13 therapy prevents brain pathology in pneumococcal meningitis.

Despite effective antibiotic therapy, brain-destructive inflammation often cannot be avoided in pneumococcal meningitis. The causative signals are mediated predominantly through TLR-recruited myeloid differentiation primary response adaptor 88 (MyD88), as indicated by a dramatic pneumococcal meningitis phenotype of Myd88-/- mice. Because lipoproteins and single-stranded RNA are crucial for recognition of Gram-positive bacteria such as Streptococcus pneumoniae by the host immune system, we comparatively analyzed the disease courses of Myd88-/- and Tlr2-/- Tlr13-/- mice. Their phenotypic resemblance indicated TLR2 and -13 as master sensors of S. pneumoniae in the cerebrospinal fluid. A neutralizing anti-TLR2 antibody (T2.5) and chloroquine (CQ) - the latter applied here as an inhibitor of murine TLR13 and its human ortholog TLR8 - abrogated activation of murine and human primary immune cells exposed to antibiotic-treated S. pneumoniae. The inhibitory effect of the T2.5/CQ cocktail was stronger than that of dexamethasone, the current standard adjunctive drug for pneumococcal meningitis. Accordingly, TLR2/TLR13 blockade concomitant with ceftriaxone application significantly improved the clinical course of pneumococcal meningitis compared with treatment with ceftriaxone alone or in combination with dexamethasone. Our study indicates the importance of murine TLR13 and human TLR8, besides TLR2, in pneumococcal meningitis pathology, and suggests their blockade as a promising antibiotic therapy adjunct.

Triad of Terror: Rapidly Progressive Austrian Syndrome in a 62-Year-Old Female.

We report a case of a 62-year-old female presenting with shortness of breath, who was subsequently diagnosed with Austrian syndrome. The patient had a complicated clinical course, including invasive central nervous system pneumococcal disease, pneumococcal bacteremia, and mitral valve vegetation with possible leaflet perforation. Despite aggressive treatment, her condition continued to worsen. We will discuss the clinical features of this disease, approaches to diagnosis and treatment, and outcomes in light of this rare condition.

NLRP3 Activation Contributes to Memory Impairment in an Experimental Model of Pneumococcal Meningitis.

Bacterial meningitis is considered a life-threatening condition with high mortality rates. In response to the infection, signaling cascades, producing pro-inflammatory mediators trigger an exacerbated host immune response. Another inflammatory pathway occurs through the activation of inflammasomes. Studies highlight the role of the NLR family pyrin domain containing 3 (NLRP3) in central nervous system disorders commonly involved in neuroinflammation. We aimed to investigate the role of NLRP3 and its inhibitor MCC950 on neurochemical, immunological, and behavioral parameters in the early and late stages of experimental pneumococcal meningitis. For this, adult male Wistar rats received an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a placebo. The animals were divided into control/saline, control/MCC950, meningitis/saline, and meningitis/MCC950. Immediately after the meningitis induction, the animals received 140 ng/kg MCC950 via intracisternal injection. For the acute protocol, 24 h after induction, brain structures were collected to evaluate cytokines, NLRP3, and microglia. In the long-term group, the animals were submitted to open field and recognition of new objects tests at ten days after the meningitis induction. After the behavioral tests, the same markers were evaluated. The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels. Although free from infection, ten days after meningitis induction, the animals in the meningitis group had elevated cytokine levels and demonstrated behavioral deficits; however, the single dose of NLRP3 inhibitor rescued the behavior deficits and decreased the brain inflammatory profile.

Cerebral vasculitis as a complication of pneumococcal meningitis: A cohort study.

OBJECTIVE: Cerebral vasculitis (CV) is a severe complication of pneumococcal meningitis (PM); whether dexamethasone use can reduce its occurrence remains to be determined. METHODS: This is a retrospective observational bicentric study analyzing all adults with proven PM hospitalized between January 2002 and December 2020 in two tertiary hospitals. Extrapolating from a standardized definition of primary angiitis of the central nervous system, we defined CV as worsened neurological symptoms associated with compatible imaging. All images were analyzed by a radiologist, and two neurologists reviewed all inconclusive cases of suspected CV for adjudication. Factors associated with CV were analyzed, including dexamethasone use. A subgroup analysis was limited to patients with a lumbar puncture at PM diagnosis. RESULTS: Among 168 patients with PM, 49 (29.2%) had CV, occurring after a median of 8 days (IQR 5-13) of PM diagnosis. In multivariate analysis (N = 151), initial CRP was associated with CV (OR 1.28 per 50-unit increase, p = 0.003), which was marginally linked with delayed hospital admission more than 48 hours after first symptoms (OR 2.39, p = 0.06) and prior NSAID intake (OR 2.94, p = 0.05). Dexamethasone administration did not impact CV occurrence. In 133 patients having undergone lumbar puncture, CSF protein level > 4.4 g/L (OR 4.50, p = 0.006) was associated with CV. CONCLUSIONS: In our cohort, CV was a frequent and severe complication of PM, often occurring in association with unduly delayed medical care, high CRP at admission, and high levels of protein in CSF.

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study.

BACKGROUND: The leading cause of acute bacterial meningitis in adults is Streptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis. METHODS AND ANALYSIS: The AddaMAP trial is a phase II, open-label, Simon's two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03480191.

Hearing outcomes in children with pneumococcal meningitis in the PCV13 era.

INTRODUCTION: Streptococcus pneumoniae, is associated with the highest incidence of post-meningitic SNHL. The exact impact of 13-valent pneumococcal conjugate vaccine (PCV) on pediatric SNHL from pneumococcal meningitis is unknown. We aimed to identify clinical factors associated with post-meningitic SNHL (pmSNHL) from pneumococcal meningitis and describe its rates based on three time periods: pre-PCV, PCV-7 and PCV13 eras. METHODS: A retrospective case-control study was performed for patients 18 years and younger diagnosed with pneumococcal meningitis from January 1, 2010 to December 31, 2020 at Children's Hospital Colorado. Demographic and clinical risk factors between those with or without SNHL were compared. Detailed hearing outcomes of those with resulting SNHL are described. RESULTS: 23 patients with CSF cultures or Meningitis/Encephalitis Panel positive for pneumococcal meningitis were identified. Twenty patients both survived the infection and had audiologic evaluation. Six patients had pmSNHL, with 50 % affected bilaterally. The rate of pmSNHL from S. pneumoniae in the PCV-13 era at our institution was similar to historical rates from the pre-PCV and PCV-7 eras. Similar proportions of patients with pmSNHL completed PCV vaccination (66.7 %) compared to those without (71.4 %). Non-PCV-13 serotypes were responsible 83 % of patients with pmSNHL versus 57 % of patients without pmSNHL. CONCLUSIONS: Despite high rates of PCV-13 uptake in our cohort, pmSNHL was still common, severe, and commonly associated with non-PCV-13 serotypes. Non-PCV-13 serotypes may be contributing to the persistently high rate of post-meningitic SNHL and the severity of SNHL. Newer pneumococcal conjugate vaccines with expanded serotypes may help mitigate the SNHL associated with pneumococcal meningitis.

Takotsubo cardiomyopathy in a 4-year-old female with pneumococcal meningitis.

A previously healthy 4-year-old female presented in cardiogenic shock with pneumococcal meningitis. Findings on echocardiogram raised suspicion for takotsubo cardiomyopathy. With supportive care, left ventricular systolic function normalised. Findings on cardiac imaging helped determine the aetiology and avoid further invasive studies or unnecessary treatment.

Streptococcus pneumoniae meningitis in a child with idiopathic nephrotic syndrome: a case report.

BACKGROUND: Children with nephrotic syndrome are at increased risk of infections, including bacterial peritonitis, pneumonia, and cellulitis. However, bacterial meningitis, a potentially life-threatening complication, has not been highlighted as an infectious complication of nephrotic syndrome in recent reviews. We report a very subtle and unusual presentation of bacterial meningitis in a child with nephrotic syndrome, which without a high index of suspicion, would have been missed. CASE PRESENTATION: A 9-year-old African-American male with a history of steroid-dependent nephrotic syndrome presented to the nephrology clinic for routine follow-up. His medications included mycophenolate mofetil and alternate-day steroids. His only complaint was neck pain and stiffness that the mother attributed to muscle tightness relieved by massage. There was no history of fever, vomiting, headache, photophobia, or altered mental status. On physical examination, he was afebrile (99 °F), but had mild periorbital swelling and edema on lower extremities. He appeared ill and exhibited neck rigidity, and demonstrated reflex knee flexion when the neck was bent. Laboratory evaluation revealed leukocytosis, elevated C-reactive protein, hypoalbuminemia, and proteinuria. Cerebrospinal fluid suggested bacterial meningitis. The patient was treated with ceftriaxone and vancomycin. Both cerebrospinal and blood cultures grew Streptococcus pneumoniae; vancomycin was discontinued. The child completed a 2-week course of ceftriaxone and was discharged home. CONCLUSIONS: A high index of suspicion is necessary in children with nephrotic syndrome treated with corticosteroids, as symptoms may be masked, and thus, a life-threatening disease be missed. Bacterial meningitis should be highlighted as a serious infection complication in children with nephrotic syndrome.

A Challenging Case of Streptococcus pneumoniae Meningitis in a 64-Year-Old Woman Who Presented with Symptoms of Cerebellar Hemorrhage.

BACKGROUND There is a recognized association between bacterial meningitis and intracranial hemorrhage. However, acute neurological symptoms at presentation, with confirmation of hemorrhage on imaging, may delay further investigations, including blood culture for diagnosing an infection. This report presents a challenging case of Streptococcus pneumoniae meningitis in a 64-year-old woman who presented with symptoms of cerebellar hemorrhage. CASE REPORT This report describes a 64-year-old woman who had a medical history of untreated diabetes mellitus. She was brought to our hospital with headache and impaired consciousness, complicated with fever. Based on the hemorrhage in the left cerebellar hemisphere detected in the head CT findings, the patient was initially diagnosed with cerebellar hemorrhage. However, a positive blood culture after 12 hours of admission made the physician consider a central nervous system infection as the cause of the hemorrhage and perform a lumbar puncture. Therefore, the patient was diagnosed with acute bacterial meningitis caused by Streptococcus pneumoniae, and antibiotic treatment was started immediately. Although her general condition improved after antibiotic treatment, her mental status did not improve completely. CONCLUSIONS This report highlights that the clinicians should be aware that bacterial meningitis may result in intracranial hemorrhage. Patients with symptoms of a hemorrhagic stroke should be thoroughly investigated to avoid a delay in the treatment of infection.

[Cranial multineuritis and transverse myelitis as complications of pneumococcal meningitis]. / Multineuritis craneal y mielitis transversa como complicaciones de una meningitis neumocócica.

INTRODUCTION: Pneumococcal meningitis is a condition associated with a high rate of morbidity and mortality. CASE REPORT: We report the clinical case of a 41-year-old man who, following meningitis caused by Streptococcus pneumoniae, developed subsequent complications such as thoracic transverse myelitis, which caused paralysis in the lower extremities, abolition of all sensory modalities and dysautonomic disorders, as well as an alteration of the anterior horn cells at the cervical level that produced paralysis in the upper extremities, but with preservation of sensibility. This implies the need for a differential diagnosis between what is known as 'poliomyelitis-like' disorder and acute disseminated encephalomyeloradiculitis. The examination and the radiological and neurophysiological study showed a full clinical recovery of the upper extremities, thanks in part to early neurorehabilitation. CONCLUSIONS: Complications of the spinal cord within the context of infection of the central nervous system are very rare. Involvement of the anterior horn cells of the spinal cord has only been described anecdotally, and no bibliographical references have been found that associate it with S. pneumoniae.

TITLE: Multineuritis craneal y mielitis transversa como complicaciones de una meningitis neumocócica.Introducción. La meningitis neumocócica es una patología que asocia una elevada tasa de morbimortalidad. Caso clínico. Presentamos el caso clínico de un varón de 41 años que, tras una meningitis causada por Streptococcus pneumoniae, tuvo como complicaciones posteriores una mielitis transversa torácica que le ocasionó una plejía en las extremidades inferiores, abolición de todas las modalidades sensitivas y trastornos disautonómicos, así como una alteración de las astas anteriores a nivel cervical que produjo plejía en las extremidades superiores, pero con conservación de la sensibilidad. Esto plantea un diagnóstico diferencial entre la afectación denominada 'poliomielitis like' y una encefalomielorradiculitis diseminada aguda. La exploración y el estudio radiológico y neurofisiológico avalaron una recuperación clínica completa en las extremidades superiores, gracias, en parte, a una neurorrehabilitación precoz. Conclusiones. Las complicaciones medulares en el contexto de una infección del sistema nervioso central son muy infrecuentes. La afectación medular de astas anteriores se ha descrito únicamente de forma anecdótica, y no se han encontrado referencias bibliográficas que la asocien con S. pneumoniae.

Pneumococcal meningitis and COVID-19: dangerous coexistence. A case report.

BACKGROUND: SARS-CoV-2 is the major cause of infections in humans since December 2019 and is top of the global health concern currently. Streptococcus pneumoniae is one of the leading pathogens of invasive bacterial diseases, including pneumonia, sepsis, and meningitis. Moreover, this bacteria is mostly responsible for secondary infections subsequent to post-viral respiratory disease. Co-infections with bacterial and viral pathogens are associated with severe course of the disease and are a major cause of mortality. In this report, we describe a rare case of COVID-19 patient with pneumococcal sepsis and meningitis of unsuccessful course. CASE PRESENTATION: A 89-year-old man, not vaccinated against SARS-CoV-2 infection, was diagnosed with COVID-19 pneumonia. Patient required oxygen therapy due to respiratory failure. The initial treatment of viral infection with tocilizumab and dexamethasone allowed for the stabilization of the patient's condition and improvement of laboratory parameters. On the 9th day of hospitalization the patient's condition deteriorated. Consciousness disorders and acute respiratory disorders requiring intubation and mechanical ventilation were observed. Brain computed tomography excluded intracranial bleeding. The Streptococcus pneumoniae sepsis with concomitant pneumoniae and meningitis was diagnosed based on microbiological culture of blood, bronchial wash, and cerebrospinal fluid examination. Despite targeted antibiotic therapy with ceftriaxone and multidisciplinary treatment, symptoms of multiple organ failure increased. On the 13th day of hospitalization, the patient died. CONCLUSIONS: Co-infections with bacterial pathogens appear to be not common among COVID-19 patients, but may cause a sudden deterioration of the general condition. Not only vascular neurological complications, but also meningitis should be always considered in patients with sudden disturbances of consciousness. Anti-inflammatory treatment with the combination of corticosteroids and tocilizumab (or tocilizumab alone) pose a severe risk for secondary lethal bacterial or fungal infections. Thus, treating a high-risk population (i.e. elderly and old patients) with these anti-inflammatory agents, require daily clinical assessment, regular monitoring of C-reactive protein and procalcitonin, as well as standard culture of blood, urine and sputum in order to detect concomitant infections, as rapidly as possible.

Rapid progressive destruction of the cochleae in an infant due to pneumococcal meningitis.

The widespread adoption of pneumococcal conjugate vaccines has reduced the incidence of Streptococcus pneumoniae infections, but has also led to the emergence of infections due to non-vaccine serotypes. A 15-month-old girl was referred to our hospital with suspected meningitis. S. pneumoniae was isolated from her cerebrospinal fluid. She was initially treated with a combination of cefotaxime and vancomycin, followed by ampicillin and vancomycin. After 7 days, the patient's condition improved and she was transferred to the general ward; however, her mother noted signs of hearing difficulties. On the 16th day of admission, we performed an auditory brainstem response test, which suggested severe bilateral hearing impairment. This was confirmed using an auditory steady-state response test after consulting with otolaryngologists. Magnetic resonance imaging revealed fibrosis of both cochleae with labyrinthitis. The patient underwent emergency cochlear implantation at a different hospital. The S. pneumoniae isolate was later identified to be serotype 10A with a PBP2x mutation, which is not covered by the conjugate vaccine and has reduced cephalosporin susceptibility. This case was characterized by highly rapid cochlear destruction, and an earlier otolaryngologist consultation may have provided a more well-organized surgery plan. Pediatricians are urged to promptly consult with otolaryngologists for patients with similar indications.

Clinical Features and Outcomes of Streptococcus pneumoniae Meningitis in Children: A Retrospective Analysis of 26 Cases in China.

BACKGROUND: Streptococcus pneumoniae is an important cause of pediatric meningitis. OBJECTIVE: The aim of this study was to analyze the clinical features and outcomes of children with pneumococcal meningitis at our hospital in China, so as to provide basis for improving the clinical treatment effect. METHODS: This retrospective analysis included patients aged <16 years treated for pneumococcal meningitis at the Department of Neurology, Children's Hospital of Shanxi (January 2014-February 2016). Clinical data were extracted from the medical records. Patients were followed up for 6 months after discharge. RESULTS: The analysis included 26 children aged 2 months to 13 years, with 17 (65.4%) aged <3 years. Presenting symptoms included fever (100%), lethargy (100%), impaired consciousness (88.5%), neck stiffness (69.2%), seizures (53.8%), and headache (50.0%). All patients had positive cerebrospinal fluid (CSF) cultures. The final treatment was vancomycin combined with a third-generation cephalosporin or other antibiotics in 25 patients. Eleven patients (42.3%) were recovered, 3 (11.5%) had neurological sequelae, and 12 (46.2%) died. Impaired consciousness (p = 0.035), cerebral hernia (p = 0.037), respiratory failure (p = 0.004), heart failure (p = 0.044), septic shock (p = 0.037), low CSF white blood cell count (p = 0.036), high CSF protein levels (p = 0.028), low white blood cell count (p = 0.036), and low blood neutrophil ratio (p = 0.016) are associated with a poor prognosis to pneumococcal meningitis. CONCLUSION: Pneumococcal meningitis is associated with a poor prognosis in many children. Poor prognosis might be related to early ineffective antibiotic therapy, a combination of systemic failure, neurological problems, and changed inflammatory response. It is important to rapid initiation of appropriate antibiotic therapy if meningitis is suspected.

Delayed cerebral thrombosis complicating bacterial meningitis.

BACKGROUND: Delayed cerebral thrombosis has been described as a potential cause of cerebrovascular complications in patients with bacterial meningitis. We report a case of delayed cerebral thrombosis in a 63-year-old woman admitted for pneumococcal meningitis. Initially, there was a good clinical evolution under treatment with steroids and antibiotics. On day 8 after admission, she was found with a decreased level of consciousness. Her neurological condition gradually worsened. Repeated brain imaging showed extensive ischemic lesions. Despite treatment with high-dose corticosteroids, the patient died. METHODS: A literature search was conducted. Data on patient characteristics, diagnosis, treatment and outcome were collected. RESULTS: To date, 28 cases with delayed cerebral thrombosis following bacterial meningitis have been reported. Streptococcus pneumoniae was the pathogen in 89% of cases. Clinical deterioration occurred in all patients, with a duration varying from 5 to 40 days between admission and deterioration. Most common symptom was altered consciousness (83%), followed by hemiparesis (52%). Brain imaging typically shows new infarctions (96%). Fifty-six percent of patients were treated with corticosteroids after deterioration. Outcome was poor with mortality rate of 46%. CONCLUSION: Delayed cerebral thrombosis presents as a clinical deterioration, typically a sudden decline in consciousness, more than 5 days after meningitis onset. Brain imaging shows new widespread ischemic lesions. Diagnosis should be made carefully, based on clinical findings and brain imaging, after excluding endocarditis. The underlying etiology remains unknown. When delayed cerebral thrombosis is suspected, high-dose corticosteroids should be started empirically. The prognosis remains poor with high mortality rates.

Vertebral osteomyelitis as a hidden cause of persistent meningeal irritation in a patient with pneumococcal meningitis: A case report.

RATIONALE: Pneumococcal meningitis generally develops from bacteremia and is often complicated by multiple organ infection. PATIENT CONCERNS: A 62-year-old man with no previous medical history developed progressive disturbance of consciousness preceded by high-grade fever and headache for a few days. DIAGNOSIS: The patient was diagnosed with pneumococcal meningitis based on meningeal irritation, polymorphonuclear cell-predominant pleocytosis of the cerebrospinal fluid (CSF) and a positive pneumococcal urinary antigen test at a different hospital. Despite the administration of meropenem and vancomycin, his consciousness worsened, and the patient was transferred to our hospital. Marked nuchal stiffness was noted. The patient showed a disturbance of consciousness, with a Glasgow Coma Scale score of E3V2M5. No significant cranial nerve palsy, motor weakness or sensory impairment was observed. CSF examination showed polynuclear cell-predominant pleocytosis of 755/µL. Transthoracic echocardiography revealed infectious endocarditis. INTERVENTIONS: After the detection of penicillin-susceptible Streptococcus pneumoniae, the antibiotic regimen was changed to aminobenzylpenicillin 12 g/d and ceftriaxone 4 g/d, which improved the patient's consciousness and CSF findings. However, marked neck stiffness and neck pain persisted; we performed a systemic investigation that revealed cervical vertebral osteomyelitis and aortic aneurysm. OUTCOMES: After surgical treatment, the patient achieved complete remission of both conditions. LESSONS: We should consider vertebral osteomyelitis as a potential complication of meningitis when nuchal stiffness persists despite an improvement in meningitis.

Cerebral venous thrombosis in pneumococcal meningitis: An autopsy study.

AIMS: Cerebral venous thrombosis (CVT) is a rare but severe complication of bacterial meningitis. The histopathological features of CVT in meningitis patients have not been described. MATERIALS AND METHODS: We studied histopathology findings of brain autopsy material from 2 patients with bacterial meningitis complicated by CVT and compared findings with those in 3 CVT patients without meningitis and 1 patient with bacterial meningitis without CVT. The histological slides were re-evaluated and assessed for the presence of thrombosis, cerebral venous sinus mural inflammation and bleeding, inflammation at the thrombosis attachment point, endothelial abnormalities, and the presence of bacteria. RESULTS: The 2 patients who died of bacterial meningitis complicated by CVT showed multifocal deep intramural inflammation in the cerebral venous sinus, whereas this was absent in patients with only bacterial meningitis or CVT. Bacteria were identified within the intramural inflammation and thrombus. CONCLUSION: We observed bacterial invasion causing multifocal deep intramural inflammation and venous wall disintegration as CVT in pneumococcal meningitis.

Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.