scholarly journals Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections

2020 ◽  
Author(s):  
Tran Tan Thanh ◽  
Climent Casals-Pascual ◽  
Nguyen Thi Han Ny ◽  
Nghiem My Ngoc ◽  
Ronald Geskus ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Bacterial Meningitis ◽  
Diagnostic Performance ◽  
Biomarker Discovery ◽  
Characteristic Curve ◽  
Accurate Identification ◽  
Cns Infections ◽  
Potential Biomarker

ABSTRACTBackgroundCentral nervous system (CNS) infections are common causes of morbidity and mortality worldwide. Rapid, accurate identification of the likely cause is essential for clinical management and the early initiation of antimicrobial therapy, which potentially improves clinical outcome.MethodsWe applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic protein biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in southern Vietnam.ResultsIn the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis. The analysis of the validation cohort showed that LCN2 could discriminate bacterial meningitis from other CNS infections, including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis (sensitivity: 0.88 (95% confident interval (CI): 0.77–0.94), specificity: 0.91 (95%CI: 0.88–0.94) and diagnostic odd ratio: 73.8 (95%CI: 31.8–171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2 and these four routine CSF markers resulted in the highest diagnostic performance for bacterial meningitis (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93–0.99).ConclusionsOur results suggest that LCN2 is a sensitive and specific biomarker for discriminating bacterial meningitis from a broad spectrum of CNS infections. A prospective study is needed to further assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.

Central Nervous System Infections

2016 ◽  
Author(s):  
Nicholas J. Johnson ◽  
David F. Gaieski
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Bacterial Meningitis ◽  
Lumbar Puncture ◽  
Clinical Manifestations ◽  
Empirical Therapy ◽  
Cns Infection ◽  
Cns Infections ◽  
Associated Conditions

Infections of the central nervous system (CNS) are among the most devastating diseases that present to the emergency department (ED). Because of the great potential for morbidity, as well as the importance of prompt treatment, emergency physicians must remain vigilant of these diseases, which are also fraught with diagnostic challenges. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of CNS infections. Figures show causes of viral meningitis, an algorithm for the initial evaluation and management of patients with a suspected CNS infection, clinical manifestations of community-acquired meningitis in patients 16 years of age and older, assessment of nuchal rigidity, Kernig sign, and Brudzinski sign for meningeal irritation, proper positioning of the patient for lumbar puncture, and a sagittal view of the lumbar puncture needle as it is advanced into the subarachnoid space. Tables list CNS pathogens based on predisposing and associated conditions, cerebrospinal fluid diagnostic studies for meningitis, adult patients who should receive computed tomography prior to lumbar puncture, classic cerebrospinal fluid characteristics in meningitis, empirical therapy for bacterial meningitis based on predisposing and associated conditions, recommended doses for antibiotics commonly used in the treatment of bacterial meningitis, and antimicrobial therapy for selected CNS infections.   This review contains 8 highly rendered figures, 7 tables, and 94 references

scholarly journals Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

2021 ◽  
Vol 11 (2) ◽  
pp. 238
Author(s):  
Keld-Erik Byg ◽  
Helle H. Nielsen ◽  
Tobias Sejbaek ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chain ◽  
Plasma Levels ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Fluid Levels

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

scholarly journals When Ventricular Cerebrospinal Fluid Assessment Misleads: Basal Meningitis and the Importance of Lumbar Puncture Sampling

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Sadid F Khan ◽  
Thornton Macauley ◽  
Steven Y C Tong ◽  
Ouli Xie ◽  
Carly Hughes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Lumbar Puncture ◽  
Cns Infection ◽  
Pathophysiological Mechanisms ◽  
Cns Infections ◽  
Fluid Assessment ◽  
Composition Gradients

Abstract The diagnosis of central nervous system (CNS) infection relies upon analysis of cerebrospinal fluid (CSF). We present 4 cases of CNS infections associated with basal meningitis and hydrocephalus with normal ventricular CSF but grossly abnormal lumbar CSF. We discuss CSF ventricular–lumbar composition gradients and putative pathophysiological mechanisms and highlight clinical clues for clinicians.

scholarly journals Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

mBio ◽  
2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Le Van Tan ◽  
H. Rogier van Doorn ◽  
Ho Dang Trung Nghia ◽  
Tran Thi Hong Chau ◽  
Le Thi Phuong Tu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Unknown Etiology ◽  
Healthy Children ◽  
Detection Rates ◽  
Cns Infections ◽  
Food Borne ◽  
Animal Reservoirs ◽  
Substantial Morbidity

ABSTRACTAcute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.IMPORTANCEAcute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology frequently remains unknown, which hampers development of therapeutic or preventive strategies. Hence, identification of novel pathogens is essential and is facilitated by current next-generation sequencing-based methods. Using such technology, we identified and characterized the full genome of a novel cyclovirus in cerebrospinal fluid (CSF) specimens from two Vietnamese patients with CNS infections of unknown etiology, which was subsequently detected in none of 122 CSF specimens from patients with noninfectious neurological disorders but 4% of 642 CSF specimens from Vietnamese patients with suspected or confirmed CNS infections. Similar detection rates in feces from healthy children suggested food-borne or orofecal transmission routes, while frequent detection in feces from Vietnamese pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further studies are needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

scholarly journals Cerebrospinal fluid lactic acid in diagnosis of meningitis

1978 ◽  
Vol 8 (1) ◽  
pp. 89-92
Author(s):  
R A Komorowski ◽  
S G Farmer ◽  
G A Hanson ◽  
L L Hause
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Lactic Acid ◽  
Bacterial Meningitis ◽  
Lactate Concentration ◽  
Clinical Situation ◽  
Rapid Diagnosis ◽  
Brain Diseases ◽  
Fungal Meningitis

Quantitative lactate determinations were performed on cerebrospinal fluids to assess their value in the rapid diagnosis of bacterial and mycotic meningitis and to evaluate their value in assessing the prognosis in these patients. Cerebrospinal fluid lactate concentrations were elevated in all patients with untreated bacterial or fungal meningitis. Lactate concentrations proved very valuable in following patients with mycotic meningitis and in differentiating aseptic from bacterial meningitis. Elevated cerebrospinal fluid lactate is not specific for meningitis. Lactate is also elevated in situations where there is central nervous system ischemia and necrosis and in patients with brain tumors. Lactate concentration is normal in chronic degenerative brain diseases. Thus, the clinical situation must be taken into account when interpreting the lactate concentrations.

scholarly journals Central nervous system candidiasis beyond neonates: Lessons from a nationwide study

2020 ◽  
Author(s):  
Hélène Chaussade ◽  
Xavier Cazals ◽  
Guillaume Desoubeaux ◽  
Gregory Jouvion ◽  
Marie-Elisabeth Bougnoux ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Vascular Complications ◽  
Intrathecal Chemotherapy ◽  
Cns Involvement ◽  
Candida Spp ◽  
Disseminated Candidiasis ◽  
Disseminated Infection ◽  
Cns Infections

Abstract Though candidiasis is the most frequent invasive fungal infection, Candida spp. central nervous system (CNS) infections are rare but severe. To further describe clinico-patho-radiological presentations of this entity, we report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included. Seventeen patients (70%) had CNS localization secondary to disseminated candidiasis (10 with hematologic malignancies [HM]; the seven other patients had infective endocarditis [IE]). Among patients with HM, seven previously had lumbar puncture for intrathecal chemotherapy, the three others had IE. Among patients with disseminated infection, magnetic resonance imaging (MRI) evidenced meningitis (17%), micro-abscesses (58%), or vascular complications (67%). Seven patients (30%) had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use, diabetes mellitus, or no identified predisposing condition (n = 1 each). All evaluated patients with isolated CNS involvement had meningitis on cerebrospinal fluid (CSF) and intracranial hypertension. For the latter patients, MRI evidenced meningitis (71%) or abscesses (57%). Among all patients, cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. CSF βDGlucan or mannan Ag were positive in respectively 86% and 80% of cases. Mortality attributed to CNS candidiasis was 42%: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection. CNS candidiasis are isolated or occur during disseminated infection in patients with HM and lumbar puncture for intrathecal chemotherapy or during IE. Clinical, radiological finding and outcome highly vary according to CNS localized versus disseminated candidiasis. Lay Summary Candida is a yeast and is the most common cause of fungal infections worldwide. Candida central nervous system (CNS) infections are rare, severe, and poorly described. We report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included (14 men, median age 51 years). Seventeen patients had CNS localization secondary to disseminated candidiasis from blood to CNS (10 with hematologic malignancies [HM], the seven other patients had infective endocarditis [IE]). Seven patients had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use (n = 1), diabetes mellitus (n = 1), or no identified risk factor (n = 1). During Candida CNS infections, brain lesions were meningitis abscesses or vascular complications. Cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. Forty-two percent of patients died from infection: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection.

CSF lactate

2020 ◽  
Vol 20 (4) ◽  
pp. 320-323
Author(s):  
Aravindhan Baheerathan ◽  
Robert DS Pitceathly ◽  
Carmel Curtis ◽  
Nicholas WS Davies
Keyword(s):  
Emergency Department ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Blood Lactate ◽  
Human Body ◽  
Anaerobic Glycolysis ◽  
Cns Infections ◽  
Csf Lactate ◽  
Neurological Infection

Lactate is produced from anaerobic glycolysis, which occurs in most tissues in the human body. Blood lactate is tested in most physiologically unwell patients in the Emergency Department and helps to guide treatment and prognosis. Cerebrospinal fluid (CSF) lactate, however, is not often measured. Various central nervous system (CNS) conditions lead to a rise in CSF lactate, including acute neurological infection, stroke, seizures and mitochondrial pathologies. This article discusses the utility and limitations of CSF lactate, highlighting specific clinical situations where it can help in the diagnosis of CNS infections and unexplained encephalopathy.

scholarly journals Dosage of lactate in the cerebrospinal fluid in infectious diseases of the central nervous system

2001 ◽  
Vol 59 (4) ◽  
pp. 843-848 ◽  
Author(s):  
Hideraldo Luis Souza Cabeça ◽  
Hélio Rodrigues Gomes ◽  
Luís dos Ramos Machado ◽  
José Antonio Livramento
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Bacterial Meningitis ◽  
Infectious Diseases ◽  
Immune Deficiency Syndrome ◽  
Viral Meningitis ◽  
Control Group ◽  
Fungal Meningitis ◽  
The Central Nervous System

This paper analyzes the diagnosis aid of the dosage of lactate in the cerebrospinal fluid (CSF) in infectious diseases of the central nervous system (CNS). We analyzed prospectively 130 samples of CSF of 116 patients with diagnoses of infectious processes in the CNS. The 130 samples of CSF were divided into five groups: 28 samples of the control group, 40 of bacterial meningitis, 22 of viral meningitis, 16 of fungal meningitis and 24 of patients presenting acquired immune deficiency syndrome (AIDS). The concentration of lactate in the CSF was elevated in the group of patients with bacterial meningitis (average = 46.2 mg/dL), fungal meningitis (average = 27.3 mg/dL) and in the AIDS group (average = 23.5 mg/dL). In the control group and viral meningitis group the lactate content in the CSF presented the reference rates according to the employed method. The lactate dosage in the CSF presented a negative correlation with glycorrhachia and positive correlation with the cellularity and total proteins of the CSF. We conclude that the lactate dosage in the CSF, although unspecific, helps to distinguish the infectious processes of the CNS.

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