The spectrum of computerized tomography (CT) findings in central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii in immunocompetent children

Cranial CT scans of eleven immunocompetent children with central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii were retrospectively reviewed. These children had an average age of 8.8 years and positive culture for C. n. var. gattii in cerebrospinal fluid. The most common signs and symptoms were headache, fever, nuchal rigidity, nausea and vomiting. No normal cranial CT was detected in any patient. Hypodense nodules were observed in all patients . The remaining scan abnormalities were as follows: nine had diffuse atrophy, six had hydrocephalus, and five had hydrocephalus coexistent with diffuse atrophy.

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AIDS: Neurological Opportunist Infections in Central London

Journal of the Royal Society of Medicine ◽

10.1177/014107688908200511 ◽

1989 ◽

Vol 82 (5) ◽

pp. 278-280 ◽

Cited By ~ 2

Author(s):

R J Guiloff

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mycobacterium Tuberculosis ◽

Herpes Zoster ◽

Toxoplasma Gondii ◽

Cryptococcus Neoformans ◽

Jc Virus ◽

Cns Infection ◽

System Involvement ◽

Opportunist Infection

Twenty six (41%) of 64 central London cases of AIDS with nervous system involvement during the course of the illness had neurological opportunist infection. Cytomegalovirus and Toxoplasma gondii were the commonest agents in 22 cases with central nervous system (CNS) infection. Eight cases had herpes zoster radiculopathy. Other infections included those caused by Cryptococcus neoformans, Mycobacterium tuberculosis and papova JC virus. Prognosis was generally poor, irrespective of whether the opportunist infection was treatable.

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045 Primary cutibacterium acnes central nervous system infection causing focal seizures: an unusual presentation of a rare disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.40 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A15.2-A15

Author(s):

Sophie E Waller ◽

Sarah Browning ◽

Elizabeth Pepper

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Central Nervous System Infection ◽

Cns Infection ◽

Delayed Presentation ◽

Pathogenic Potential ◽

Focal Seizures ◽

Device Infection ◽

Cutibacterium Acnes ◽

Neurosurgical Intervention

IntroductionCutibacterium acnes is a Gram positive, anaerobic bacterium of low pathogenic potential that forms part of the normal cutaneous flora. Although most often identified as a contaminant in culture of microbiological specimens, it is commonly implicated in both postoperative wound and implantable device infection. Neurosurgical device infections secondary to C. acnes are well recognised and are likely secondary to bacterial contamination from the skin during surgery. Indolent infection characterised by delayed presentation of weeks to months following intervention is common. C. acnes infection involving the central nervous system (CNS) in the absence of previous neurosurgical intervention is rare, but has been described following dental or mastoid infections and following facial trauma. A further case series has reported de novo C. acnes CNS infection occurring in the absence of these recognised risk factors, but with clinical features of meningitis being common to all.Methods and resultsWe describe a unique case of primary C. acnes extra-dural collection in a previously well patient with no neurosurgical history presenting with sub-acute focal seizures and progressive focal leptomeningeal thickening on MRI.ConclusionC. acnes CNS infection can occur in the immunocompetent and in the absence of neurosurgical intervention.

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Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab104 ◽

2021 ◽

Author(s):

Nanda Ramchandar ◽

Nicole G Coufal ◽

Anna S Warden ◽

Benjamin Briggs ◽

Toni Schwarz ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Next Generation Sequencing ◽

Usual Care ◽

Transcriptomic Analysis ◽

Cns Infection ◽

Metagenomic Sequencing ◽

Next Generation ◽

Cns Infections ◽

Generation Sequencing

Abstract Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. Usual care testing by culture and PCR is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with CNS infections. Methods We conducted a prospective multi-site study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to one of three tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusion Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

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Central nervous system involvement in Chagas' disease: an updating

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651993000200001 ◽

1993 ◽

Vol 35 (2) ◽

pp. 111-116 ◽

Cited By ~ 42

Author(s):

José Eymard Homem Pittella

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Chagas Disease ◽

Acute Phase ◽

Central Nervous System Involvement ◽

Cns Infection ◽

Cns Involvement ◽

Anatomical Basis ◽

Immunosuppressed Patients ◽

Acute Form

A review was made of the available literature on central nervous system (CNS) involvement in Chagas' disease. Thirty-one works concerning the acute nervous form and 17 others dealing with the chronic nervous form, all presenting neuropathologic studies, were critically analysed. Based on this analysis, an attempt was made to establish the possible natural history of CNS involvement in Chagas' disease. Among others, the following facts stand out: 1) the initial, acute phase of Trypanosoma cruzi infection is usually asymptomatic and subclinical; 2) only a small percentage of cases develop encephalitis in the acute phase of Chagas' disease; 3) the symptomatic acute forms accompanied by chagasic encephalitis are grave, with death ensuing in virtually all cases as a result of the brain lesions per se or of acute chagasic myocarditis, this being usually intense and always present; 4) individuals with the asymptomatic acute form and with the mild symptomatic acute form probably have no CNS infection or, in some cases, they may have discrete encephalitis in sparse foci. In the latter case, regression of the lesions may be total, or residual inflammatory nodules of relative insignificance may persist. Thus, no anatomical basis exists that might characterize the existence of a chronic nervous form of Chagas' disease; 5) reactivation of the CNS infection in the chronic form of Chagas' disease is uncommon and occurs only in immunosuppressed patients.

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Morbillivirus Infection of the Mouse Central Nervous System Induces Region-Specific Upregulation of MMPs and TIMPs Correlated to Inflammatory Cytokine Expression

Journal of Virology ◽

10.1128/jvi.75.17.8268-8282.2001 ◽

2001 ◽

Vol 75 (17) ◽

pp. 8268-8282 ◽

Cited By ~ 36

Author(s):

Seng-Thuon Khuth ◽

Hideo Akaoka ◽

Axel Pagenstecher ◽

Olivier Verlaeten ◽

Marie-Françoise Belin ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mouse Model ◽

Neurological Disorders ◽

Dynamic Balance ◽

Brain Structures ◽

Cytokine Expression ◽

Tissue Inhibitors Of Metalloproteinases ◽

Cns Infection ◽

Necrosis Factor Alpha

ABSTRACT Viral infection of the central nervous system (CNS) can result in perturbation of cell-to-cell communication involving the extracellular matrix (ECM). ECM integrity is maintained by a dynamic balance between the synthesis and proteolysis of its components, mainly as a result of the action of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). An MMP/TIMP imbalance may be critical in triggering neurological disorders, in particular in virally induced neural disorders. In the present study, a mouse model of brain infection using a neurotropic strain of canine distemper virus (CDV) was used to study the effect of CNS infection on the MMP/TIMP balance and cytokine expression. CDV replicates almost exclusively in neurons and has a unique pattern of expression (cortex, hypothalamus, monoaminergic nuclei, hippocampus, and spinal cord). Here we show that although several mouse brain structures were infected, they exhibited a differential pattern in terms of MMP, TIMP, and cytokine expression, exemplified by (i) a large increase in pro-MMP9 levels, in particular in the hippocampus, which occurred mainly in neurons and was associated with in situ gelatinolytic activity, (ii) specific and significant upregulation of MT1-MMP mRNA expression in the cortex and hypothalamus, (iii) an MMP/TIMP imbalance, suggested by the upregulation of TIMP-1 mRNA in the cortex, hippocampus, and hypothalamus and of TIMP-3 mRNA in the cortex, and (iv) a concomitant region-specific large increase in expression of Th1-like cytokines, such as gamma interferon, tumor necrosis factor alpha, and interleukin 6 (IL-6), contrasting with weaker induction of Th2-like cytokines, such as IL-4 and IL-10. These data indicate that an MMP/TIMP imbalance in specific brain structures, which is tightly associated with a local inflammatory process as shown by the presence of immune infiltrating cells, differentially impairs CNS integrity and may contribute to the multiplicity of late neurological disorders observed in this viral mouse model.

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Adaptation of Cryptococcus neoformans to Mammalian Hosts: Integrated Regulation of Metabolism and Virulence

Eukaryotic Cell ◽

10.1128/ec.05273-11 ◽

2011 ◽

Vol 11 (2) ◽

pp. 109-118 ◽

Cited By ~ 63

Author(s):

Jim Kronstad ◽

Sanjay Saikia ◽

Erik David Nielson ◽

Matthias Kretschmer ◽

Wonhee Jung ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cryptococcus Neoformans ◽

Central Carbon Metabolism ◽

Yeast Cells ◽

Phagocytic Cells ◽

Content Type ◽

The Central Nervous System ◽

Mechanisms Of Adaptation ◽

Complex Integration

ABSTRACTThe basidiomycete fungusCryptococcus neoformansinfects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system. Recent studies provide insights into mechanisms of adaptation during this transition that include the expression of antiphagocytic functions, the remodeling of central carbon metabolism, the expression of specific nutrient acquisition systems, and the response to hypoxia. Specific transcription factors regulate these functions as well as the expression of one or more of the major known virulence factors ofC. neoformans. Therefore, virulence factor expression is to a large extent embedded in the regulation of a variety of functions needed for growth in mammalian hosts. In this regard, the complex integration of these processes is reminiscent of the master regulators of virulence in bacterial pathogens.

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Autonomous requirements of the Menkes disease protein in the nervous system

AJP Cell Physiology ◽

10.1152/ajpcell.00130.2015 ◽

2015 ◽

Vol 309 (10) ◽

pp. C660-C668 ◽

Cited By ~ 10

Author(s):

Victoria L. Hodgkinson ◽

Sha Zhu ◽

Yanfang Wang ◽

Erik Ladomersky ◽

Karen Nickelson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Copper Deficiency ◽

Copper Homeostasis ◽

Signs And Symptoms ◽

Menkes Disease ◽

Copper Transporter ◽

Sensorimotor Deficits ◽

The Central Nervous System

Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a Nes mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle ( mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a Nes mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a Nes mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients.

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Clinical Analysis of Intravenous and Oral Sequential Treatment With Voriconazole for Candida Central Nervous System Infection in Six Premature Infants

Frontiers in Pharmacology ◽

10.3389/fphar.2021.631293 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yingying Zhu ◽

Xiaohui Gong ◽

Zhiling Li ◽

Danni Wang ◽

Chongbing Yan

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Side Effects ◽

Blood Culture ◽

Kidney Function ◽

Premature Infants ◽

Sequential Treatment ◽

Cns Infection ◽

Significant Difference ◽

Liver And Kidney

Objective: The aim of the study was to observe the clinical efficacy and safety of intravenous and oral sequential treatment with voriconazole for Candida central nervous system (CNS) infection in premature infants.Methods: The study included retrospective analysis of the clinical data of six premature infants with Candida CNS infection admitted to the neonatology department in Shanghai Children’s Hospital between November 2016 and November 2019. By reviewing the characteristics of voriconazole based on the literature, it showed that infants without gastrointestinal dysfunction could be effectively treated by intravenous and oral sequential therapy with voriconazole (both 7 mg/kg/dose, every 12 h). Clinical manifestations, the time required for the cerebrospinal fluid (CSF), blood culture, nonspecific infection markers such as platelets and C-reactive protein (CRP) to turn normal, and drug-related side effects were observed and recorded in the process of treatment. All data were statistically analyzed by T test and Mann–Whitney U test.Results: A total of six premature infants were diagnosed with Candida CNS infection, two cases were diagnosed by a positive CSF culture and four cases were clinically diagnosed. Blood culture was positive for Candida in five cases. Among the 6 patients, 4 cases were Candida albicans and 2 cases were Candida parapsilosis. All the six cases were cured. After 3–5 days of treatment, symptoms such as lethargy, apnea, and feeding intolerance were improved and disappeared; a repeated blood culture turned negative in 3–7 days; CSF returned to normal in 15 ± 9 days on an average. Brain abscess, meningeal inflammation, and other infectious lesions were cleared on cranial magnetic resonance imaging (MRI) after treatment. The average total course of voriconazole was 61 ± 29 days, and the average oral treatment was 28 ± 15 days. No Candida recurrence was found during the treatment, and no drug-related side effects such as skin rash, liver and kidney function impairment, or visual abnormalities were found. The white blood cells, CSF glucose/plasma glucose ratio, and protein in CSF were significantly improved after the treatment (p < 0.05). No statistically significant difference was identified in the liver and kidney function indexes (p > 0.05).Conclusion: Voriconazole is a relatively safe and effective alternative treatment for Candida CNS infection in preterm infants. No severe drug-related side effects were detected.

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ANTICHOLINERGIC POISONING: TREATMENT WITH PHYSOSTIGMINE

PEDIATRICS ◽

10.1542/peds.52.3.449 ◽

1973 ◽

Vol 52 (3) ◽

pp. 449-451

Author(s):

Barry H. Rumack

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acetic Acid ◽

Specific Treatment ◽

Signs And Symptoms ◽

The Body ◽

Sweat Glands ◽

Exocrine Glands ◽

Anticholinergic Syndrome ◽

The Central Nervous System

The increased incidence of poisoning by overdoses of commonly used drugs with anticholinergic properties (Table I) and the general lack of knowledge concerning a specific treatment for these poisons warrants a summary of the problem at this time. Some plants containing anticholinergic alkaloids are also included in this group as they may also be taken intentionally or accidentally. Drugs with anticholinergic properties primanly antagonize acetylcholine competitively at the neuroreceptor site. Cardiac muscle, exocrine glands, and smooth muscle are most markedly affected.1 Action of the inhibitors is overcome by increasing the level of acetylcholine naturally generated in the body through inhibiting the enzyme (choline esterase) which normally prevents accumulation of excess acetylcholine. It does this by hydrolyzing that compound to inactive acetic acid and choline. Agents which inhibit this enzyme, so that acetylcholine accumulates at the neuroreceptor sites, are called anticholine esterases. Physostigmine, one of the anticholine esterases which is a tertiary amine, crosses into the central nervous system and can reverse both central and peripheral anticholinergic actions2. Neostigmine and pyridostigmine are also anticholine esterases but they are quaternary amines and are capable of acting only outside the central nervous system because of solubility and ionization characteristics. The anticholinergic syndrome has both central and peripheral signs and symptoms. Central toxic effects include anxiety, delirium, disorientation, hallucinations, hyperactivity, and seizures.2 Severe poisoning may produce coma, medullary paralysis, and death. Peripheral taxicity is characterized by tachycardia, hyperpyrexia, mydriasis, vasodilatation, urinary retention, diminution of gastrointestinal motility, decrease of secretion in salivary and sweat glands, and loss of secretions in the pharynx, bronchi, and nasal passages.

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Impact of a Multiplex Polymerase Chain Reaction Assay on the Clinical Management of Adults Undergoing a Lumbar Puncture for Suspected Community-Onset Central Nervous System Infections

Antibiotics ◽

10.3390/antibiotics9060282 ◽

2020 ◽

Vol 9 (6) ◽

pp. 282

Author(s):

Matthew A. Moffa ◽

Derek N. Bremmer ◽

Dustin Carr ◽

Carley Buchanan ◽

Nathan R. Shively ◽

...

Keyword(s):

Central Nervous System ◽

Polymerase Chain Reaction ◽

Nervous System ◽

Clinical Management ◽

Intervention Group ◽

Cns Infection ◽

Chain Reaction ◽

Post Intervention ◽

Polymerase Chain ◽

Community Onset

Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt diagnostic evaluation and correct antimicrobial treatment. A retrospective, multicenter, pre/post intervention study was performed to evaluate the impact that the BioFire® FilmArray® meningitis/encephalitis (ME) panel run in-house had on the clinical management of adult patients admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was the effect that this intervention had on herpes simplex virus (HSV) polymerase chain reaction (PCR) turnaround time (TAT). Secondary outcomes included the effect that this intervention had on antiviral days of therapy (DOT), total antimicrobial DOT, and hospital length of stay (LOS). A total of 81 and 79 patients were included in the pre-intervention and post-intervention cohorts, respectively. The median HSV PCR TAT was significantly longer in the pre-intervention group (85 vs. 4.1 h, p < 0.001). Total antiviral DOT was significantly greater in the pre-intervention group (3 vs. 1, p < 0.001), as was total antimicrobial DOT (7 vs. 5, p < 0.001). Pre-intervention hospital LOS was also significantly longer (6.6 vs. 4.4 days, p = 0.02). Implementing the ME panel in-house for adults undergoing an LP for a suspected community-onset CNS infection significantly reduced the HSV PCR TAT, antiviral DOT, total antimicrobial DOT, and hospital LOS.

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