ABSTRACT
Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis.
Subject(s)
Arthritis, Rheumatoid , Biomarkers , Matrix Metalloproteinase 9 , Meningitis , Female , Humans , Male , Arthritis, Rheumatoid/cerebrospinal fluid , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/complications , Biomarkers/cerebrospinal fluid , Biomarkers/blood , Follow-Up Studies , Matrix Metalloproteinase 9/cerebrospinal fluid , Matrix Metalloproteinase 9/blood , Meningitis/cerebrospinal fluid , Meningitis/blood , Meningitis/diagnosisSubject(s)
Diagnostic Errors , Magnetic Resonance Imaging , Meningioma , Meningitis , Humans , Meningitis/diagnosis , Meningitis/blood , Meningitis/immunology , Meningioma/diagnosis , Meningioma/diagnostic imaging , Immunoglobulin G/blood , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/diagnostic imaging , Male , Female , Middle Aged , HypertrophyABSTRACT
Steroid responsive meningitis-arteritis (SRMA) in dogs causes severe inflammation of meningeal arteries leading to generalized meningitis with possible neurological signs, as well as a systemic inflammatory response. The etiology and exact pathogenesis are unknown, but an immune-mediated origin has been suggested and is supported by a positive response to immunosuppressive treatment with corticosteroids. A collection of clinical and paraclinical characteristics may be highly indicative of SRMA, but a single and conclusive diagnostic test or biomarker is currently not available. The aim of this review is to provide an overview of the current understanding and knowledge on SRMA, with special emphasis on potential biomarkers and their applicability in the diagnostic work-up. Though no specific markers for SRMA currently exist, clinically useful markers include IgA and several acute phase proteins e.g. C-reactive protein. A frequent problem of both acknowledged and proposed biomarkers, is, however, their inability to effectively differentiate SRMA from other systemic inflammatory conditions. Other proposed diagnostic markers include genetic markers, acute phase proteins such as serum amyloid A, cytokines such as interleukin-17 and CC-motif ligand 19, endocannabinoid receptors and heat shock protein 70; these suggestions however either lack specificity or need further investigation.
Subject(s)
Arteritis/veterinary , Dog Diseases/diagnosis , Meningitis/veterinary , Acute-Phase Proteins/analysis , Animals , Arteritis/diagnosis , Biomarkers/blood , Dogs , Immunoglobulin A/blood , Meningitis/blood , Meningitis/diagnosisABSTRACT
Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82-6190.50; serum median 24.48, IQR 11.93-49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.
Subject(s)
Cytokines/cerebrospinal fluid , Meningitis/immunology , Meningoencephalitis/immunology , West Nile Fever/immunology , West Nile virus/immunology , Aged , Cytokines/blood , Cytokines/immunology , Female , Humans , Interleukin-17/blood , Interleukin-17/cerebrospinal fluid , Interleukin-17/immunology , Interleukin-4/blood , Interleukin-4/cerebrospinal fluid , Interleukin-4/immunology , Male , Meningitis/blood , Meningitis/cerebrospinal fluid , Meningitis/virology , Meningoencephalitis/blood , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/virology , Middle Aged , Th17 Cells/immunology , West Nile Fever/genetics , West Nile Fever/virology , West Nile virus/genetics , West Nile virus/physiologyABSTRACT
BACKGROUND: Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. CONCLUSIONS: The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF.
Subject(s)
Angiostrongylus cantonensis/isolation & purification , Eosinophilia/diagnosis , Meningitis/diagnosis , Strongylida Infections/diagnosis , Adult , Animals , Eosinophilia/blood , Eosinophilia/parasitology , Female , Humans , Leukocyte Count , Male , Meningitis/blood , Meningitis/parasitology , Middle Aged , Strongylida Infections/blood , Strongylida Infections/parasitologyABSTRACT
To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes (p < 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = 0.001 and p < 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included (p < 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present.
Subject(s)
Central Nervous System Infections/diagnosis , Diagnosis, Differential , Encephalitis, Tick-Borne/diagnosis , Meningitis/diagnosis , Adult , Aged , Central Nervous System Infections/blood , Central Nervous System Infections/cerebrospinal fluid , Central Nervous System Infections/virology , Encephalitis, Tick-Borne/blood , Encephalitis, Tick-Borne/cerebrospinal fluid , Encephalitis, Tick-Borne/virology , Female , Herpesvirus 3, Human/pathogenicity , Humans , Immunity, Humoral/genetics , Immunity, Humoral/immunology , Immunoglobulin M/blood , Leukocytosis/blood , Leukocytosis/cerebrospinal fluid , Leukocytosis/diagnosis , Leukocytosis/virology , Magnetic Resonance Imaging , Male , Meningitis/blood , Meningitis/cerebrospinal fluid , Meningitis/virology , Middle Aged , Simplexvirus/immunology , Simplexvirus/pathogenicityABSTRACT
OBJECTIVE: The incidence of complications due to acute otitis media (AOM) in childhood has decreased significantly with the use of new antibiotics in recent years. However, acute mastoiditis (AM) is still the most common complication that can lead to further intracranial conditions with high morbidity. Our study aimed to evaluate the clinical characteristics of children with AM and identify possible indicators for further intracranial complications associated with this condition. METHODS: Children hospitalized in our clinic with a diagnosis of AM were reviewed. Demographic data, disease-related symptoms, types of complications accompanied by AM, medical/surgical treatments modalities, and culture results were screened. The patients were divided into two groups as those with and without intracranial complications (ICCs). Routine complete blood count tests, biochemical analysis, and C-reactive protein (CRP) level measurement were evaluated and compared between the groups. RESULTS: Of the 28 AM patients, five (17.9%) had isolated AM. Complications associated with AM included sub-periosteal abscess (28.6%), facial paralysis (25%), meningitis (17.9%), meningitis with sigmoid sinus thrombosis (7.1%), and meningitis with cerebellar abscess (3.6%). Eight patients developed ICCs (28.6%), of whom three had more than one complication. Ceftriaxone was found to be the first-line medical treatment (57.1%). Streptococcus pneumoniae was the most common pathogen isolated from the cultures (42.9%). Three patients (10.7%) were treated non-surgically, eight (28.6%) with myringotomy and ventilation tube (VT) insertion, eight patients (28.6%) with abscess drainage and VT insertion, and nine (32.1%) with cortical mastoidectomy and VT insertion. There was no significant difference between the patients with and without ICCs in terms of complete blood count parameters. The CRP level and the CRP-albumin ratio were significantly higher in patients with ICCs than those without these complications (p < 0.001). CONCLUSION: AM remains to be the most common complication of AOM in childhood and can lead to further life-threatening conditions. Additional interventions according to the type of the complication with VT insertion is safe and effective in the management of AM. In patients with AM, it is of great importance to determine whether there is an accompanying ICC. The CRP-albumin ratio is a simple and reliable calculation to detect ICCs in patients with AM.
Subject(s)
Mastoiditis/complications , Mastoiditis/therapy , Otitis Media/complications , Otitis Media/therapy , Acute Disease , Adolescent , Anti-Bacterial Agents/therapeutic use , Blood Cell Count , Brain Abscess/blood , Brain Abscess/etiology , Brain Abscess/surgery , C-Reactive Protein/metabolism , Ceftriaxone/therapeutic use , Child , Child, Preschool , Drainage , Facial Paralysis/blood , Facial Paralysis/etiology , Female , Humans , Infant , Male , Mastoidectomy , Mastoiditis/blood , Mastoiditis/microbiology , Meningitis/blood , Meningitis/etiology , Middle Ear Ventilation , Otitis Media/blood , Otitis Media/microbiology , Serum Albumin/metabolism , Sinus Thrombosis, Intracranial/blood , Sinus Thrombosis, Intracranial/etiology , Streptococcus pneumoniaeABSTRACT
Objectives To determine whether there is a cut off value of serum C-reactive protein (CRP) associated with a higher risk of meningitis in suspected early onset sepsis (EOS) (onset birth to 7 days of life). Methods A retrospective cohort study on neonates admitted in neonatal intensive care unit at McMaster Children's Hospital from January 2010 to 2017 and had lumbar puncture (LP) and CRP for workup of EOS. Included subjects had either (a) non-traumatic LP or (b) traumatic LP with cerebral spinal fluid (CSF) polymerase chain reaction or gram stain or culture-positive or had received antimicrobials for 21 days. Excluded were CSF done for metabolic errors, before cytomegalovirus (CMV) treatment; from ventriculo-peritoneal (VP) shunts; missing data and contamination. Neonates were classified into definite and probable meningitis and on the range of CRP. We calculated sensitivity, specificity, and likelihood ratios for CRP values; and area under the receiver operating characteristic (AUROC) curve. Results Out of 609 CSF samples, 184 were eligible (28 cases of definite or probable meningitis and 156 controls). Sensitivity, specificity, predictive values, likelihood ratios, and AUROC were too low to be of clinical significance to predict meningitis in EOS. Conclusions Serum CRP values have poor discriminatory power to distinguish between subjects with and without meningitis, in symptomatic EOS.
Subject(s)
C-Reactive Protein/analysis , Cerebrospinal Fluid/microbiology , Meningitis , Neonatal Sepsis , Area Under Curve , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal/statistics & numerical data , Leukocyte Count/methods , Likelihood Functions , Male , Meningitis/blood , Meningitis/etiology , Neonatal Sepsis/blood , Neonatal Sepsis/diagnosis , Neonatal Sepsis/physiopathology , Outcome Assessment, Health Care , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Spinal Puncture/methodsABSTRACT
BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a highly complex disease with very high mortality and morbidity. About one-third of SAH patients suffer from systemic infections, predominantly pneumonia, that can contribute to excess mortality after SAH. Immunodepression is probably the most important mechanism leading to infections. Interleukin-10 (IL-10) is a master regulator of immunodepression, but it is still not clear if systemic IL-10 levels contribute to immunodepression, occurrence of infections and clinical outcome after SAH. METHODS: This explorative study included 76 patients with SAH admitted to our neurointensive care unit within 24 h after ictus. A group of 24 patients without any known intracranial pathology were included as controls. Peripheral venous blood was withdrawn on day 1 and day 7 after SAH. Serum was isolated by centrifugation and stored at -80 °C until analysis. Serum IL-10 levels were determined by enzyme-linked immunoassay (ELISA). Patient characteristics, post-SAH complications and clinical outcome at discharge were retrieved from patients' record files. RESULTS: Serum IL-10 levels were significantly higher on day 1 and day 7 in SAH patients compared to controls. Serum IL-10 levels were significantly higher on day 7 in patients who developed any kind of infection, cerebral vasospasm (CVS) or chronic hydrocephalus. Serum IL-10 levels were significantly higher in SAH patients discharged with poor clinical outcome (modified Rankin Scale (mRS) 3-6 or Glasgow Outcome Scale (GOS) 1-3). CONCLUSION: Serum IL-10 might be an additional useful parameter along with other biomarkers to predict post-SAH infections.
Subject(s)
Healthcare-Associated Pneumonia/blood , Interleukin-10/blood , Meningitis/blood , Subarachnoid Hemorrhage/blood , Aged , Biomarkers/blood , Female , Healthcare-Associated Pneumonia/epidemiology , Healthcare-Associated Pneumonia/etiology , Humans , Intracranial Aneurysm/blood , Intracranial Aneurysm/complications , Male , Meningitis/epidemiology , Meningitis/etiology , Middle Aged , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/etiologyABSTRACT
BACKGROUND: Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF. Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject. METHODS: Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values. RESULTS: A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases. CONCLUSIONS: Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture.
Subject(s)
Leukocytosis/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Blood Culture , Cerebrospinal Fluid/microbiology , Cerebrospinal Fluid/virology , Diagnostic Tests, Routine , Humans , Leukocyte Count , Meningitis/blood , Meningitis/mortality , Polymerase Chain Reaction , Retrospective Studies , Spinal PunctureABSTRACT
BACKGROUND: Back pain is a leading reason for patients to seek medical attention. Although musculoskeletal causes are common, patients can also present with rarer etiologies. CASE DESCRIPTION: A 50-year-old man presented with 2 months of isolated upper back pain initially suspected to be secondary to overuse muscular strain. During the next 3 months, his pain worsened, and he developed lower extremity dysesthesia and subjective weakness, despite normal neurological examination findings. Nonrevealing laboratory workup included normal muscle enzymes, C-reactive protein, urinalysis, and human leukocyte antigen B27. Magnetic resonance imaging revealed a normal brain but a hypointense C7-T5 epidural mass, prompting a neurosurgical recommendation for laminectomy with evacuation of the suspected hematoma. His symptoms fully and promptly resolved after a 5-day course of prednisone 40 mg. When his symptoms recurred within 2 months, he underwent T4-T5 laminectomy with biopsy of a mass confluent with the dura mater. Initial pathological examination revealed fibrotic tissue of unclear etiology with polyclonal lymphoid infiltrate but no malignant cells, vasculitis, or granulomas. After months of recurrent, steroid-responsive symptoms, he presented to the rheumatology clinic. Repeat spinal magnetic resonance imaging demonstrated progression of epidural thickening with suspected spinal cord compression. Previous biopsy samples were then immunostained for IgG4, revealing focally dense IgG4-positive plasma cells, up to 29 cells per high power field, consistent with spinal IgG4-related hypertrophic pachymeningitis. He began rituximab therapy with a prednisone taper and demonstrated symptomatic and neurologic improvement with successful withdrawal from corticosteroids. CONCLUSIONS: To the best of our knowledge, the present case represents the 12th reported case of spinal IgG4-related hypertrophic pachymeningitis. An early diagnosis and treatment could prevent progression to permanent neurological impairment and functional disability.
Subject(s)
Immunoglobulin G/blood , Meningitis/blood , Spinal Cord Compression/blood , Spinal Cord , Back Pain/blood , Back Pain/diagnostic imaging , Back Pain/etiology , Humans , Hypertrophy/blood , Hypertrophy/complications , Hypertrophy/diagnostic imaging , Male , Meningitis/complications , Meningitis/diagnostic imaging , Middle Aged , Spinal Cord/diagnostic imaging , Spinal Cord Compression/complications , Spinal Cord Compression/diagnostic imagingSubject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/blood , Clinical Decision-Making/methods , Procalcitonin/blood , Bacteremia/blood , Bacteremia/drug therapy , Bacterial Infections/drug therapy , Biomarkers/blood , Humans , Meningitis/blood , Meningitis/drug therapy , Sepsis/blood , Sepsis/drug therapyABSTRACT
The study included 64 patients with serous meningitis, in which the heart rate variability (HRV) spectrum, the content of ACTH and STH in serum was studied in the course of the commonly accepted treatment. The purpose of the study was to analyze the dynamics of indicators of functional state of the autonomic nervous system in correlation with changes of adrenocorticotropic and somatotropic hormones in patients with serous meningitis. According to the results, serous meningitis were predominantly moderate in severity, with generalization in the clinical picture dominated through general toxicosis, general cerebral and meningeal syndromes, but changes in the spectral parameters of HRV showed a marked imbalance with a shift in the functional activity of the autonomic nervous system towards vagotonia in combination with an ACTH level increase and STH decrease in serum (p<0.01). The purpose of the study was to analyze the dynamics of indicators of functional state of the autonomic nervous system in correlation with changes of adrenocorticotropic and somatotropic hormones in patients with serous meningitis. According to the results, serous meningitis were predominantly moderate in severity, with generalization in the clinical picture dominated by general toxicosis, general cerebral and meningeal syndromes, but changes in the spectral parameters of HRV showed a marked imbalance with a shift in the functional activity of the autonomic nervous system towards vagotonia in combination with an ACTH level increase and STH decrease in serum (p<0.01).
Subject(s)
Adrenocorticotropic Hormone/blood , Autonomic Nervous System/physiology , Autonomic Nervous System/physiopathology , Heart Rate/physiology , Human Growth Hormone/blood , Meningitis/physiopathology , Adolescent , Adult , Aged , Growth Hormone , Humans , Meningitis/blood , Middle Aged , Young AdultABSTRACT
Here we reported a Chinese case of bilateral peripheral facial paralysis (PFP) in human immunodeficiency virusc (HIV) infected population. A 38-year-old homosexual male patient was referred to our hospital for bilateral facial paralysis. 21 days prior to admission he had developed high fever, chills, headache, fatigue, general malaise, nausea and vomiting. Neurological examination revealed bilateral ptosis of lower lip and cheeks, as well as failure of bilateral eyes closure. Analysis of cerebrospinal fluid (CSF) revealed pleocytosis, a marked rise of micro total protein and a marked rise of intrathecal lgG synthesis. The result of HIV-1 serology was positive by ELISA and that was confirmed by western blot. His CD4 + cell count was 180 cells/mm 3. HIV-1 viral load in CSF was almost 10 times higher than that in plasma. The patient's condition improved steadily and experienced complete resolution of bilateral PFP after 2 months.
Subject(s)
Facial Paralysis , HIV Infections , HIV-1 , Meningitis , Adult , Facial Paralysis/blood , Facial Paralysis/pathology , Facial Paralysis/physiopathology , HIV Infections/blood , HIV Infections/pathology , HIV Infections/physiopathology , Humans , Male , Meningitis/blood , Meningitis/pathology , Meningitis/physiopathologyABSTRACT
Hypertrophic pachymeningitis (HP) is a rare neurologic disease causing inflammatory fibrous thickening of the brain and spinal dura mater. We investigated the cerebrospinal fluid cytokine profile of HP by measuring 28 cytokines/chemokines/growth factors with a multiplexed fluorescent immunoassay in 8 patients with HP (6 idiopathic, 1 IgG4-related, 1 anti-neutrophil cytoplasmic antibody-related), and 11 with other non-inflammatory neurologic diseases (OND). Interleukin (IL)-4, IL-5, IL-9, IL-10, TNF-α, and CXCL8/IL-8 levels were significantly higher in idiopathic HP (IHP) than OND. Cluster analyses disclosed two major clusters: one mainly consisted of IHP and the other of OND, suggesting a unique cytokine profile in IHP.
Subject(s)
Chemokines/cerebrospinal fluid , Cytokines/cerebrospinal fluid , Intercellular Signaling Peptides and Proteins/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Meningitis/diagnosis , Aged , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Chemokines/blood , Cytokines/blood , Female , Humans , Intercellular Signaling Peptides and Proteins/blood , Male , Meningitis/blood , Middle Aged , Th2 Cells/metabolismABSTRACT
BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cross Infection/blood , Cross Infection/cerebrospinal fluid , Daptomycin/pharmacokinetics , Meningitis/blood , Meningitis/cerebrospinal fluid , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Cross Infection/drug therapy , Daptomycin/administration & dosage , Female , Humans , Infusions, Intravenous , Male , Meningitis/drug therapy , Middle Aged , Prospective Studies , Young AdultABSTRACT
Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA). A 59-year-old man presented with a 10-day history of right-sided frontal headache and a 7-day history of subacute left-sided weakness. He had no history of RA. He was febrile (38.2°C). Left ankle dorsiflexion and plantarflexion were graded at 4+/5. He developed focal onset motor seizures. He was intermittently febrile with minimal improvement despite intravenous antivirals and antimicrobials. Serology revealed elevated rheumatoid factor 88.2 IU/mL and anti-cyclic citrullinated peptide (anti-CCP) IgG >340 AU/mL. Initial cerebrospinal fluid (CSF) was predominantly lymphocytic 96%, with elevated protein 672 mg/L and normal glucose 3.4 mmol/L. Interval CSF revealed newly low glucose 2.6 mmol/L. Extensive CSF microbiology tests were negative. CSF cytology confirmed reactive lymphocytes. MRI brain revealed right frontoparietal leptomeningeal enhancement. Brain and leptomeningeal biopsy demonstrated florid leptomeningeal mixed inflammatory infiltrate without granulomas. The combination of elevated anti-CCP IgG, erosive arthropathy, CSF lymphocytosis, asymmetrical leptomeningeal enhancement and biopsy findings confirmed RM.
Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Meningitis/blood , Meningitis/cerebrospinal fluid , Administration, Intravenous , Administration, Oral , Aftercare , Anti-Citrullinated Protein Antibodies/blood , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Biopsy , Brain/diagnostic imaging , Glucocorticoids/therapeutic use , Headache/diagnosis , Headache/etiology , Humans , Joint Diseases/diagnosis , Joint Diseases/etiology , Lymphocytosis/cerebrospinal fluid , Magnetic Resonance Imaging/methods , Male , Meningitis/diagnosis , Meningitis/diagnostic imaging , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Rare Diseases , Rheumatoid Factor/blood , Seizures/diagnosis , Seizures/etiology , Treatment OutcomeABSTRACT
Diagnostic procedures are based on establishing certain conditions and then checking if those conditions are satisfied by a given individual. When the diagnostic procedure is based on a continuous marker, this is equivalent to fix a region or classification subset and then check if the observed value of the marker belongs to that region. Receiver operating characteristic curve is a valuable and popular tool to study and compare the diagnostic ability of a given marker. Besides, the area under the receiver operating characteristic curve is frequently used as an index of the global discrimination ability. This paper revises and widens the scope of the receiver operating characteristic curve definition by setting the classification subsets in which the final decision is based in the spotlight of the analysis. We revise the definition of the receiver operating characteristic curve in terms of particular classes of classification subsets and then focus on a receiver operating characteristic curve generalization for situations in which both low and high values of the marker are associated with more probability of having the studied characteristic. Parametric and non-parametric estimators of the receiver operating characteristic curve generalization are investigated. Monte Carlo studies and real data examples illustrate their practical performance.
Subject(s)
Leukocyte Count/statistics & numerical data , Meningitis/blood , Models, Statistical , Speech Acoustics , Datasets as Topic , Female , Humans , Machine Learning , Male , Monte Carlo Method , ROC CurveABSTRACT
BACKGROUND: Recent National Institute for Health and Care Excellence (NICE) CG149 guidelines suggest considering performing a lumbar puncture (LP) to investigate for meningitis in early-onset sepsis in a neonate when a C-reactive protein (CRP) level >10mg/L, but the evidence for this recommendation is poorly defined. METHODS: Data on trust-wide LP protocols, neonatal meningitis incidence, lumbar punctures, and CRP levels seen in cases of neonatal meningitis were asked of all 137 trusts in England that recorded a birth in 2017. Our local Kingston Hospital data on every LP performed was obtained to estimate the specificity of CRP rises. RESULTS: 73/123 (59.3%) of trusts follow the NICE CG149 recommendation of considering an LP if the CRP >10mg/L. The national incidence of neonatal meningitis was 0.467/1,000 births, and an LP was performed in 1.37% of all babies, which was significantly higher in trusts considering the CRP > 10mg/L cut-off. A CRP > 10mg/L cut-off sensitivity was 88.9% based on the highest CRP level 4 days around the LP from national data of 199 cases; specificity was 78.8% based on our single-unit analysis. CONCLUSIONS: Proposing a universal CRP > 10mg/L cut-off for a lumbar puncture has been counter-productive in England. Following it generates significantly more LPs, to the point that 40.7% of trusts have chosen not to follow it. It also has poor sensitivity missing over 11% of meningitis. We therefore do not recommend a universal cut-off, rather considering the whole clinical picture (including prematurity) when considering whether to do an LP.
Subject(s)
C-Reactive Protein/analysis , Meningitis/diagnosis , Spinal Puncture , England/epidemiology , Gestational Age , Guideline Adherence , Humans , Incidence , Infant, Newborn , Meningitis/blood , Meningitis/epidemiology , Practice Guidelines as Topic , Sensitivity and Specificity , Spinal Puncture/statistics & numerical dataABSTRACT
BACKGROUND: Bacterial meningitis is a paediatric emergency with high mortality and morbidity requiring prompt diagnosis and treatment. Clinically, it is often difficult to differentiate between bacterial and non-bacterial meningitis. Several studies have demonstrated the raised values of serum procalcitonin (PCT) in bacterial infections including meningitis but without definite cut-off guidelines. Hence, this study was done to evaluate serum PCT as a marker to differentiate bacterial and non-bacterial meningitis in children and assess its efficacy. METHODS: It was a cross-sectional study done over a period of 5 months (Aug 2016-Dec 2016) in the department of Paediatrics, B P Koirala Institute of Health Sciences (BPKIHS). Fifty children aged 3 months to 15 years with suspected meningitis were enrolled and investigated with relevant investigations like complete blood counts, and cerebrospinal fluid (CSF) analysis along with serum PCT. Patients were classified into bacterial (22) and non-bacterial meningitis (28) according to clinical & CSF findings and data analysed using SPSS software. RESULTS: Serum PCT levels were significantly higher in bacterial meningitis group (median = 2.04 (1.2-3.18) ng/ml) compared with non-bacterial meningitis (median = 0.35 (0.18-0.35) ng/ml); p < 0.001. The sensitivity and specificity of serum PCT in diagnosis of bacterial meningitis at cut-off level of 0.5 ng/ml were 95.45% and 84.61% respectively. Procalcitonin showed maximum area under receiver operating characteristics (ROC) curve 0.991 (0.974-1.00) (p < 0.001) compared to total leukocyte count and CSF cytochemistry. CONCLUSION: Serum PCT has high sensitivity and specificity for early diagnosis of bacterial meningitis in children. Hence it can be a useful adjunct in differentiating bacterial and non-bacterial meningitis for prompt and better management of the children.