Central Nervous System Infection Research Articles

Thoracolumbar myelocele repair: how I do it

BackgroundMyelocele is a rare form of open spina bifida. Surgical repair is recommended prenatally or in the first 48 h. In some cases, the repair may be delayed, and specific surgical factors need to be considered.MethodWe give a brief overview of the surgical anatomy, followed by a description of the surgical repair of a thoracolumbar Myelocele in an 11-month-old child.ConclusionSurgical repair of the Myelocele stabilizes the neurological status, prevents local and central nervous system infections. The understanding of Myelocele anatomy enables its removal while preserving as much healthy tissue as possible and restoring normal anatomy.

Imaging of Central Nervous System Infections in the Immunocompromised Patient

Immunocompromised patients are susceptible to the same infections as immunocompetent individuals and have an additional unique risk for atypical infections in the central nervous system (CNS). Many CNS infections carry a poor prognosis if not treated promptly, so it is prudent for radiologists to recognize key findings and have a high level of suspicion in immunocompromised patients. Moreover, a patient may have no known deficiency but can present with an atypical CNS infection as their first sign of an immunocompromised state, thus allowing the radiologist to be the first to suggest specific workup such as HIV testing. Because different infection sources (bacterial, fungal, and parasitic) have separate treatments, it is highly valuable to guide management in the right direction early in the diagnostic workup. This article discusses common opportunistic infections observed in the immunocompromised patient, primarily focusing on neuroimaging findings and pertinent clinical background and treatment for each disease entity. This article also emphasizes the importance of familiarity with the differential diagnosis for ring-enhancing lesions within the CNS.

Imaging of Central Nervous System Infections in the Immunocompromised Patient

Imaging of Central Nervous System Infections in the Immunocompromised Patient

Story of an acute stroke and dual central nervous system infection

Story of an acute stroke and dual central nervous system infection

Ceftaroline Fosamil as a Potential Treatment for Central Nervous System Infections in Children

Abstract Ceftaroline has been reported to show efficacy in limited adult clinical case studies including a report of a patient with a methicillin-resistant Staphylococcus aureus (MRSA) infection of a ventriculopleural shunt, and in 2 reports for use as a salvage therapy in a case of an epidural abscess infected with MRSA, as well as a case of methicillin-resistant Staphylococcus epidermidis (MRSE) ventriculostomy-related infection. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of ceftaroline in healthy adults and neurosurgical patients have been assessed to develop population PK models used to perform simulations to evaluate the probability of target attainment of different ceftaroline dosing regimens for central nervous system (CNS) infections. Results from the simulations indicated that the penetration of ceftaroline into the cerebrospinal fluid was dependent on the degree of meningeal inflammation, suggesting that inflammation associated with infection would provide adequate antibiotic exposure, similar to other β-lactam antibiotics. Ceftaroline has a potential, unique role as a β-lactam antibiotic in the treatment of MRSA and coagulase negative staphylococci causing CNS infections as an alternative to vancomycin, the current standard of care. Support for treatment of CNS infections may be derived from further cerebrospinal fluid PK studies followed by PK/PD modeling prior to the conduct of prospective phase 2/3 clinical studies aimed at assessing the efficacy and safety of ceftaroline for the treatment of pediatric CNS infections. Ceftaroline's penetration enhanced by meningeal inflammation suggests that the drug could be a candidate to treat MRSA CNS infections.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Initially Presenting as Septic Meningoencephalitis in a 16-Year-Old Male.

We describe a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in a 16-year-old patient who initially presented with clinical features of septic meningoencephalitis. This case outlines the importance of considering a diagnosis of MOGAD in patients who fail to improve with appropriate antimicrobial therapy or show a positive clinical response to glucocorticoids (often used in treatment of meningococcal meningitis). We emphasise the importance of recognising that an infectious prodrome can precede MOGAD. A 16-year-old male was admitted with vomiting, fever, headache, photophobia and altered mental state. He was treated for meningoencephalitis with initial clinical improvement. Lumbar puncture findings were suggestive of viral meningoencephalitis. During admission the patient went through several periods of transient clinical and biochemical improvement, alternating with periods of symptomatic relapse. On day 17 of admission, he was transferred to a tertiary centre for suspected autoimmune disseminated meningoencephalitis (ADEM) and two days later, he suffered a catastrophic neurological decline with new dysarthria, dysphagia, aphasia, horizontal nystagmus and facial paralysis. He made a remarkable neurological recovery after commencing treatment with IV immunoglobulin, IV methylprednisolone and plasma exchange, with complete resolution of symptoms. MOGAD can run a variable course and present soon after a central nervous system infection, making the diagnosis more challenging. Nonetheless, patients can achieve a full neurological recovery with early recognition, diagnosis and treatment of this rare entity. Autoimmune encephalitis can be preceded by an infectious prodrome which makes the diagnosis more challenging.Autoimmune encephalitis can run a subacute and fluctuating course with transient periods of symptomatic improvement preceding a rapid neurological decline.Glucocorticoids often used in treatment of patients with meningococcal meningitis may lead to transient symptomatic improvement in patients with autoimmune encephalitis, masking the diagnosis.MRI findings of demyelination in autoimmune encephalitis may lag behind clinical symptoms by days to weeks.

Plausible use of citicoline as an adjuvant in central nervous system infections: A case report and review of the literature

Plausible use of citicoline as an adjuvant in central nervous system infections: A case report and review of the literature

A case of central nervous system infection with Scedosporium boydii

AbstractScedosporium boydii is considered an opportunist fungal pathogen in immunocompromised patients. It also causes serious and fatal central nervous system infections. In this study, a man with brain abscesses infected with S. boydii was diagnosed using multiple methods, including microscopy, culture combined with Matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MOLDI‐TOF MS), internal transcribed spacer sequencing and Metagenomic next‐generation sequencing (mNGS). This successful diagnosis highlights the importance of using a variety of techniques to identify and treat infections caused by this dangerous fungus.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n=8) and A. levis (n=1), from brain abscess (n=4), respiratory tract (n=3), and corneal scraping (n=2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

Comparison of Clinical Characteristics in Patients with Febrile Seizures Based on Prior COVID-19 Infection

Purpose: Febrile seizures (FSs) are neurological events associated with fever, typically occurring in children between 6 months and 5 years of age in the absence of central nervous system infection. Growing evidence suggests that coronavirus disease 2019 (COVID-19) can cause immune system dysregulation. This study compared the clinical characteristics of patients with FS based on whether they had experienced prior COVID-19 infection.Methods: A retrospective analysis was conducted of the medical records of 114 patients with FS who visited Inje University Sanggye Paik Hospital between January 2019 and December 2022. Results: The study cohort included 70 (61.4%) boys and 44 (38.6%) girls, with a mean age of 22.99±11.68 months at seizure onset. Among the 114 patients with FS, 19 had a history of COVID-19, while 95 did not. These groups differed significantly in the interval between the onset of fever and seizure. Specifically, when using a 12-hour threshold for analysis, a significantly greater proportion of patients with a history of COVID-19 exhibited intervals exceeding 12 hours compared to those without such a history. No significant differences were noted regarding sex, age, seizure frequency, personal history of FS, or family history of FS or epilepsy between the groups.Conclusion: Pediatric patients with FS and prior COVID-19 infection exhibited longer intervals between the onset of fever and seizure compared to those without previous COVID-19 infection. This finding suggests that COVID-19 may influence the mechanisms underlying FS. To better understand this relationship, long-term follow-up studies with larger cohorts are warranted.

Point prevalence surveys of antibiotic prescribing in children at a tertiary hospital in a resource constraint, low-income sub-Saharan African country—the impact of an antimicrobial stewardship program

BackgroundResistance to multiple antibiotics by several pathogens has been widely described in children and has become a global health emergency. This is due to increased use by parents, caregivers, and healthcare providers. This study aims to describe the prevalence rates of antibiotic prescribing, ascertain the impact of antimicrobial stewardship programs, and target improving the quality of antibiotic prescribing in the paediatric population over time in a hospital.MethodA point prevalence survey of antibiotic use was performed yearly for 4 years to monitor trends in antibiotic prescribing. Data from all patients admitted before 8 a.m. on the day of the PPS were included. A web-based application designed by the University of Antwerp was used for data entry, validation, and analysis (http://www.global-pps.com).ResultsA total of 260 children, including 90 (34.6%) neonates and 170 (65.4%) older children, were admitted during the four surveys. Overall, 179 (68.8%) patients received at least one antibiotic. In neonates, the prevalence of antibiotic use increased from 78.9 to 89.5% but decreased from 100 to 58.8% in older children. There was a reduction in the use of antibiotics for prophylaxis from 45.7 to 24.6%. The most frequently prescribed antibiotic groups were third generation cephalosporins and aminoglycosides. The most common indications for antibiotic prescription were sepsis in neonates and central nervous system infection in older children. The documentation of reason in notes increased from 33 to 100%, while the stop-review date also increased from 19.4 to 70%.ConclusionThe indicators for appropriate antibiotic prescription improved over time with the introduction of antibiotic stewardship program in the department.

Bacterial Aggregation in Cerebral Spinal Fluid: The Extent it Occurs and the Clinical Ramifications.

Bacteria can form aggregates in synovial fluid that are resistant to antibiotics, but the ability to form aggregates in cerebral spinal fluid (CSF) is poorly defined. Consequently, the aims of this study were to assess the propensity of four bacterial species to form aggregates in CSF under various conditions. To achieve these aims, bacteria were added to CSF in microwell plates and small flasks at static and different dynamic conditions with the aid of an incubating shaker. The aggregates that formed were assessed for antibiotic resistance and the ability of tissue plasminogen activator (TPA) to disrupt these aggregates and reduce the number of bacteria present when used with antibiotics. The results of this study show that under dynamic conditions all four bacteria species formed aggregates that were resistant to high concentrations of antibiotics. Yet with static conditions, no bacteria formed aggregates and when the CSF volume was increased, only Staphylococcus aureus formed aggregates. Interestingly, the aggregates that formed were easily dispersed by TPA and significant (p < 0.005) decreases in colony-forming units were seen when a combination of TPA and antibiotics were compared to antibiotics alone. These findings have clinical significance in that they show bacterial aggregation does not habitually occur in central nervous system infections, but rather occurs under specific conditions. Furthermore, the use of TPA combined with antibiotics may be advantageous in recalcitrant central nervous system infections and this provides a pathophysiological explanation for an unusual finding in the CLEAR III clinical trial.

Neurological Diseases and Prevalence of Antineuronal Antibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 – A National Cohort Study

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic disease caused by mutations in the autoimmune regulator gene. Although the disease-associated autoantibodies mostly target endocrine organs, autoantibodies from patients with APS-1 bind also to rat brain structures. The patients often have GAD65-antibodies, that can cause autoimmune encephalitis. However, neurological manifestations of APS-1 have not been systematically explored. We conducted a retrospective chart review on 44 Finnish patients with APS-1 (median age 38 years, 61% females) and collected all their neurological diagnoses. To assess the prevalence of serum antineuronal antibodies in APS-1, serum samples of 24 patients (median age 36 years, 63% females) were analyzed using a fixed cell-based assay. Of the 44 APS-1 patients, 10 (23%) had also received a diagnosis of a neurological disease. Of these neurological comorbidities, migraine (n = 7; 16%), central nervous system infections (n = 3; 7%), and epilepsy (n = 2; 5%) were the most prevalent. Other diagnoses recorded for single patients were axonal sensorimotor polyneuropathy, essential tremor, idiopathic intracranial hypertension, ischemic stroke, and trigeminal neuralgia. Serum antineuronal antibodies were detected in 42% of patients tested (10/24, 50% females, median age 42 years), GAD65 antibodies being the most common finding. Antibodies against glycine and aquaporin 4 were found in low titers. In four patients, relatively high titers of GAD65 antibodies without coexisting type 1 diabetes were found, but none presented with GAD65-encephalitis. Our study suggests an association between APS-1 and neurological disorders, the mechanisms of which are to be further investigated.

Meningitis in Children: Still a Can't-Miss Diagnosis.

Although vaccination and antimicrobial treatment have significantly impacted the frequency and outcomes of meningitis in children, meningitis remains a critical can't-miss diagnosis for children, where early recognition and appropriate treatment can improve survival and neurologic outcomes. Signs and symptoms may be nonspecific, particularly in infants, and require a high index of suspicion to recognize potential meningitis and obtain the cerebrospinal fluid studies necessary for diagnosis. Understanding the pathogens associated with each age group and specific risk factors informs optimal empirical antimicrobial therapy. Early treatment and developmental support can significantly improve the survival rates and lifelong neurodevelopment of children with central nervous system infections.

Concerns of Performance Evaluation on Central Nervous System Infection Pathogen Metagenome Sequencing Reagent

From the perspective of the performance evaluation, concerns of the range of pathogens, establishment of enterprise reference material, reaction system study and analytical performances evaluation of central nervous system infection pathogen metagenome sequencing reagent are briefly described, including study methods and quality control requirements. This study is intended to increase the research and development efficiency of products, and contribute to the development of associated industry.

Comparison of endoscopic third ventriculostomy versus cerebrospinal fluid shunt procedures for the treatment of pediatric hydrocephalus in Taiwan.

Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National Health Insurance Research Database. A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% forthe CSF shunt group and 26.4% forthe ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. Our data indicates ETV is a betteroperative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.

New-Onset Refractory Status Epilepticus Caused by Autoimmune Encephalitis May Have a Better Prognosis than when due to Other Causes

Objective. To explore whether the new-onset refractory status epilepticus caused by autoimmune encephalitis has a better prognosis. Methods. This retrospective observational study enrolled patients with NORSE who were admitted from January 2015 to February 2024. The clinical data and clinical outcomes of the patients were collected and analyzed, and the primary outcome was seizures still at follow-up. Statistical analyses were performed using SPSS software V.22.0. Results. Among the 42 patients with NORSE, 15 (35.7%) had autoimmune encephalitis (AE), 3 (7.1%) patients had central nervous system infections, 24 (57.1%) patients had an unknown etiology, and 4 (9.5%) patients died in the hospital. Modified Rankin scale (MRS) scores at discharge of NORSE patients in the autoimmune encephalitis group and non-AE group were compared (P=0.339). After 4 years of follow-up, analysis of patients who still had seizures showed that the only risk factor was etiology and that patients with nonautoimmune encephalitis etiology were more prone to later epilepsy (P=0.030 (OR=16.767, 95% CI: 1.454-213.395)). The MRS scores of the AE group and non-AE group were compared (P≤0.001), with the autoimmune group having a better functional outcome. Significance. The overall prognosis of patients with autoimmune encephalitis may be better than that of patients with other etiologies, and later epilepsy is more likely in patients with nonautoimmune encephalitis. However, this result requires further validation in larger studies with more data.

Neutrophil extracellular trap-associated protein in cerebrospinal fluid for prognosis evaluation of adult bacterial meningitis: a retrospective case-control study.

Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.

Assessment of disease pattern and drug utilization among neurology intensive care unit patients in a developing country: an observational analysis

ABSTRACT Objective This study aimed to assess the disease pattern and drug utilization among admitted patients in a tertiary-care hospital’s neurology intensive care unit (neuro ICU). Methods A prospective observational cohort study was conducted between August 2022 and January 2023. Patients of any age and gender admitted to the neuro ICU were included, but those who declined to participate were excluded. Demographics, clinical, and medication details were consistently gathered and maintained until discharge. The World Health Organization (WHO)/International Network of Rational Use of Drugs (INRUD) prescribing indicators and the Anatomical Therapeutic Chemical (ATC) classification/Defined Daily Dose (DDD) system were used to evaluate drug use. Results A total of 516 patients were included, predominantly male (65.1%), with an average age of 54.62 ± 15.02 years. The most common diagnosis was stroke [72.3%, comprised of hemorrhagic (46.7%) and ischemic (25.6%)], followed by seizure disorders (6.6%), and central nervous system infections (5.4%). Patients received an average of 7.8 medications, 32.3% prescribed by generic name, 16.0% antibiotics, 74.1% injections, and 100% essential drugs. A (28.5%), C (19.2%), N (17.3%), J (19.2%), B (13.5%), and R (2.3%) were commonly prescribed ATC classes of medications. Number of DDDs was maximum for pantoprazole and furosemide. Based on discharged status, 41.0% were discharged on request, 24.8% against medical advice, 23.8% routine, and 10.2% mortality during hospitalization. Conclusion Our study reveals a high prevalence of hemorrhagic stroke, especially among men, diverging from global ischemic stroke trends. Irregular hypertension treatment is the primary cause, exacerbated by low healthcare knowledge in rural areas, where patients often discharge on request, probably due to poor socio-economic conditions. Urgent public awareness campaigns and further research are needed to address this elevated hemorrhagic stroke incidence.

Listeria monocytogenes: a rare cause of rhomboencephalitis in an immunocompetent patient.

We present an unusual case of Listeria monocytogenes rhomboencephalitis in a young, healthy patient. Although L. monocytogenes meningitis is usually associated with immunodeficiency, rhomboencephalitis is more commonly seen in immunocompetent patients. The wide differential for rhomboencephalitis can create a diagnostic challenge. Without prompt pathogen identification and appropriate antibiotic regimen, L. monocytogenes central nervous system infections can be fatal. Cerebro-Spinal Fluid (CSF) Polymerase Chain Reaction (PCR) aided a prompt diagnosis and adjustment of therapy to achieve a good patient outcome.