scholarly journals Clinical Significance of Positive Results of the BioFire Cerebrospinal Fluid FilmArray Meningitis/Encephalitis Panel at a Tertiary Medical Center in the United States

Author(s):  
Greer Waldrop ◽  
Jason Zucker ◽  
Alexandra Boubour ◽  
Sara Radmard ◽  
Daniel A. Green ◽  
...  

Context.— The FilmArray Meningitis/Encephalitis (ME) panel is the first US Food and Drug Administration–cleared multiplex polymerase chain reaction panel for the detection of central nervous system infections. While the assay's performance characteristics have been described, the real-world significance of positive results has not been fully characterized. Objective.— To evaluate the clinical significance of positive ME panel results in a tertiary care medical center in New York, New York. Design.— Four physicians independently performed retrospective clinical assessments of all positive ME panel results at Columbia University Irving Medical Center, including the Children's Hospital of New York, during an 18-month period. Each reviewer determined the likelihood of central nervous system infection for all cases and whether cases fit Brighton diagnostic criteria for meningitis, encephalitis, or meningoencephalitis. Results.— Among 119 cases, there was 75% positive agreement (95% CI, 54%–89%) between ME panel results and clinical consensus, which varied among panel targets. Conclusions.— The ME panel showed good agreement with expert clinical consensus for patients presenting with acute meningitis/encephalitis. Factors contributing to clinically insignificant ME positive results included low pretest probability, traumatic lumbar puncture, specimen contamination, and detection of incidental viral targets such as human herpesvirus 6. Notably, the ME panel detected more than twice the number of cases of bacterial meningitis detected by culture alone, particularly among patients receiving empiric antimicrobial therapy before lumbar puncture. Appropriate test use and contextual interpretation of results are critical to leveraging the advantages of the platform while avoiding potential pitfalls.

2010 ◽  
pp. 4749-4752
Author(s):  
Roger A. Barker ◽  
Wendy Phillips ◽  
R. Rhys Davies

Lumbar puncture provides the means to sample cerebrospinal fluid for diagnostic purposes and to remove it for some therapeutic purposes. The procedure allows measurement of the pressure of cerebrospinal fluid, its cytological composition, biochemical content, and microbial as well as serological characteristics. Indications—the commonest diagnostic indications are clinical suspicion of central nervous system infection (meningitis, encephalitis), subarachnoid haemorrhage, and demyelinating diseases (central and peripheral); the commonest therapeutic indications are idiopathic intracranial hypertension and for intrathecal administration of drugs....


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5389-5389 ◽  
Author(s):  
Megan M. Herr ◽  
Paul M. Barr ◽  
David Q Rich ◽  
Nimish Mohile

Abstract Background Secondary central nervous system lymphoma (SCNSL) is a rare complication of non-Hodgkin lymphoma (NHL) and is almost always fatal. In a review of 14 studies, SCNSL occurs in 2.3% to 10% of NHL patients and in 5% of diffuse large B-Cell lymphoma (DLBCL) patients. Median survival is 2 to 6.5 months from time of central nervous system (CNS) involvement. In this study, we sought to determine the factors that influence survival in SCNSL. Methods In a retrospective chart review with Institutional Review Board approval, all patients with SCNSL were identified from pathology reports and ICD-9 codes (198.3) using inpatient and outpatient clinic visits at the University of Rochester Medical Center, Rochester, New York from January 1st, 2005 to September 30th, 2013. Pathology reports were used to determine the total number of lymphoma patients diagnosed at URMC during this time period, which was used to calculate the incidence of SCNSL. Descriptive statistics and Kaplan-Meier curves were estimated using SAS 9.3 (Cary, NC). Results Forty-nine patients (median age = 60) developed SCNSL from DLBCL (32), transformed disease (5), marginal zone (3), Burkitts (3), lymphoplasmacytic (1), mantle cell (1), chronic lymphocytic leukemia (1), PTLD-DLBCL (1), or T-cell lymphoma (1). The cumulative incidence of secondary CNS disease in DLBCL was 3% during the study period. The majority of patients had stage IV disease (68.9%) and an elevated LDH at diagnosis. CNS prophylaxis was prescribed in 10.6% of all SCNSL patients and 12.5% in the DLBCL subset. Eighty-five percent of patients had other sites of metastases, with the majority of metastases occurring in the bone marrow, bone, lung, and liver. Patients developed CNS disease in the CSF (61%) or in the brain parenchyma (55%) or both (16%). Of the 27 patients with parenchymal involvement, 9 did not have a biopsy, but 5 had biopsy proven CSF involvement, resulting in a total of 4 unconfirmed cases, 3 of which were DLBCL. 12% of patients were asymptomatic; the other 88% presented with symptoms including headaches (33%), visual changes (29%), motor weakness (20%), cognitive problems (16%), and speech disturbances (14%). Treatment of SCNSL included a combination of treatments: methotrexate (63%), Rituxan (41%), cytarabine (39%), radiation (27%), and CHOP (20%). The median survival from diagnosis of SCNSL was 3.1 months in all patients and 2.6 months in DLBCL patients. In patients with leptomeningeal involvement only, patients that developed this involvement within 30 days of their initial NHL diagnosis were more likely to survive past 1 year (55.6%; 95% CI 0.23, 0.88) than patients who developed leptomeningeal involvement after 30 days (7.7%; 95% CI -0.07, 0.22) (p-value 0.02). Conclusion Over a period of 8.5 years, 49 NHL patients developed secondary CNS disease at a medical center in Western New York. Thirty-two out of the 49 NHL patients had DLBCL with secondary CNS disease. The cumulative incidence of secondary CNS disease in DLBCL is 3%, which is similar to what was reported in previous studies. The majority of SCNSL patients presented with neurologic symptoms. Our population closely resembles previously reported cohorts in characteristics and survival which remains poor. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Anjana Sasidharan ◽  
Dithi Banerjee ◽  
Christopher J. Harrison ◽  
Rangaraj Selvarangan

Picornaviruses including Enterovirus species A-D (EV) and Parechovirus species A (PeV-A) are the leading reported causes of pediatric central nervous system infections in the United States. We investigated the molecular epidemiology of EV and PeV-A over 10 years, in cerebrospinal fluid (CSF) collected from children seen at Children’s Mercy -Kansas City (CMKC) during 2007 through 2016. The overall prevalence for EV was 16% (862/5362) and 7% (271/4016) for PeV. Among all picornavirus CSF detections EV was 76% and PeV-A was 24%. Multiple EV types co-circulated each year with a total of 31 EV types detected in the 10-year period; majority belonged to EV-B species (96%). Two PeV-A types were detected; PeV-A3 was the dominant PeV-A type (95%). Top five picornaviruses (PeV-A3, 26%; E30, 11%; E6 10%; E18 9%, E9 7%) in the CSF of infants accounted for two-third of all detections and PeV-A3 was the leading picornavirus detected. Routine testing and reporting of PeV-A in addition to EV, especially in children under 6 months old with acute febrile illnesses, could reduce hospital stays and antibiotic usage.


2017 ◽  
Vol 13 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Ajay Kumar Mishra ◽  
Vanjare Harshad Arvind ◽  
Divya Muliyil ◽  
Cijoy K Kuriakose ◽  
Anu Anna George ◽  
...  

Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.


2019 ◽  
Vol 6 (2) ◽  
pp. 375
Author(s):  
Ruchi Jha ◽  
Anil Kumar Jaiswal

Background: Scrub typhus is an emerging epidemic in India. Its course can be complicated by involvement of Respiratory system, cardiovascular system, gastrointestinal system and central nervous system. Central nervous system involvement can lead to major morbidity and mortality.Methods: It is an observational study conducted in the Department of Pediatrics, Patna Medical College and Hospital, Patna from January 2016 to August 2018.  All cases of AES who were serologically proven to be due to scrub typhus were clinically examined, signs and symptoms were noted, and complete blood counts were done. Lumbar puncture was done, and CSF was sent for analysis of cells, sugar and protein, IgM for scrub typhus in CSF, gram staining and CSF culture.Results: Seventy-eight cases were tested positive for scrub typhus. Incidence of scrub typhus among AES cases was 19.4% in the study. Among cases of Scrub typhus, a male predominance and sex ratio was 1.68. Age at presentation ranged from 2 months to 12 years with a mean age of 7.28 years. Most of the cases were seen in the months of September and October with a mini peak in the month of March. Fever and Altered consciousness were present in all the cases. Among laboratory investigations, thrombocytopenia was the most common feature followed by raised Transaminases. CSF Analysis shows mildly increased cell count with lymphocytic predominance and presence of few polymorphs, sugar mildly decreased, and protein mildly raised.Conclusions: Scrub typhus is an important causative agent of AES in the Eastern parts of India. It should be suspected in cases which present as AES with symptoms of hepatosplenomegaly, thrombocytopenia, and elevated liver enzymes in addition to dengue encephalitis which forms its close differential.


Author(s):  
Rina A Ferguson ◽  
Joshua C Herigon ◽  
Brian R Lee ◽  
Mari M Nakamura ◽  
Jason G Newland

Abstract Ceftriaxone is one of the most common antibiotics prescribed for hospitalized children in the United States. However, ceftriaxone is not dosed consistently. Sepsis/serious bacterial infection had high dosing variability. Dosing for central nervous system infection was frequently suboptimal. Future efforts should focus on optimizing and standardizing ceftriaxone dosing.


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