Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.

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Enteroviral and Herpes Simplex Virus Central Nervous System Infections in Infants <90 Days Old: A Paediatric Investigators’ Collaborative Network on Infections in Canada (PICNIC) Study

10.21203/rs.2.20993/v3 ◽

2020 ◽

Author(s):

Dara Petel ◽

Michelle Barton ◽

Christian Renaud ◽

Lynda Ouchenir ◽

Jason Brophy ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Cns Infection ◽

Collaborative Network ◽

Cns Infections ◽

Young Infants ◽

Csf Pleocytosis ◽

Simplex Virus

Abstract Background The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or on predictors of unfavorable outcome. Methods In this cross-sectional retrospective study, seven centers from the Pediatric Investigators Collaborative Network on Infections in Canada identified infants <90 days of age with CNS infection proven to be due to enterovirus (EV) or herpes simplex virus (HSV) January 1, 2013 through December 31, 2014. Results Of 174 CNS infections with a proven etiology, EV accounted for 103 (59%) and HSV for 7 (4%). All HSV cases and 41 (40%) EV cases presented before 21 days of age. Four HSV cases (57%) and 5 EV cases (5%) had seizures. Three (43%) HSV and 23 (23 %) EV cases lacked cerebrospinal fluid (CSF) pleocytosis. HSV cases were more likely to require ICU admission (p=0.010), present with seizures (p=0.031) and have extra-CNS disease (p<0.001). Poor long-term outcomes were more common in infants who had seizures. Conclusions Viruses accounted for approximately two-thirds of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis.

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Enteroviral and Herpes Simplex Virus Central Nervous System Infections in Infants <90 Days Old: A Paediatric Investigators’ Collaborative Network on Infections in Canada (PICNIC) Study

10.21203/rs.2.20993/v2 ◽

2020 ◽

Author(s):

Dara Petel ◽

Michelle Barton ◽

Christian Renaud ◽

Lynda Ouchenir ◽

Jason Brophy ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Cns Infection ◽

Collaborative Network ◽

Cns Infections ◽

Young Infants ◽

Csf Pleocytosis ◽

Simplex Virus

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Viral Central Nervous System Infections in Infants <90 Days Old: A Paediatric Investigators’ Collaborative Network on Infections in Canada (PICNIC) Study

10.21203/rs.2.20993/v1 ◽

2020 ◽

Author(s):

Dara Petel ◽

Michelle Barton ◽

Christian Renaud ◽

Lynda Ouchenir ◽

Jason Brophy ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Empiric Therapy ◽

Cross Sectional Study ◽

Cns Infection ◽

Collaborative Network ◽

Cross Sectional ◽

Cns Infections ◽

Young Infants ◽

Csf Pleocytosis

Abstract Background The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or that are predictors of unfavorable outcome. Methods In this cross-sectional study, the Pediatric Investigators Collaborative Network on Infections in Canada identified infants <90 days of age with CNS infection proven to be due to viruses. Results Of 174 proven CNS infections, viral causes accounted for 111 (64%) including enterovirus (EV) (N=103; 93%), HSV (N=7; 6%) and human parechovirus (HPeV) (N=1; 1%). All HSV cases and 45 (43%) non-HSV cases presented before 21 days of age. HSV cases were more likely to require ICU admission (p=0.010), present with seizures (p=0.031) and have extra-CNS disease (p<0.001). Three HSV cases (43%) did not have seizures while 4 (57%) HSV and 33 (32%) non-HSV cases lacked cerebrospinal fluid (CSF) pleocytosis. Conclusions Viruses account for about half of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis.

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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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Combination Antifungal Therapy in the Treatment ofScedosporium apiospermumCentral Nervous System Infections

Case Reports in Infectious Diseases ◽

10.1155/2013/589490 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Andrés F. Henao-Martínez ◽

José R. Castillo-Mancilla ◽

Michelle A. Barron ◽

Aran Cunningham Nichol

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Antifungal Therapy ◽

Successful Treatment ◽

Surgical Debridement ◽

Prolonged Treatment ◽

Cns Infection ◽

Scedosporium Apiospermum ◽

Cns Infections

Treatment ofScedosporium apiospermumcentral nervous system (CNS) infection typically consists of an azole in combination with surgical debridement. This approach requires prolonged treatment and carries a high associated mortality. We present two cases of the successful treatment ofS. apiospermumCNS infections with the combination of voriconazole and terbinafine.

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Viral Infections of the Central Nervous System in Qatar: Epidemiology, Pathogenesis and Clinical Outcomes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.707 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S305-S305

Author(s):

Fatma Ben Abid ◽

Mohammed Abukhattab ◽

Obada Salameh ◽

Ahmed Gohar ◽

Muna Al Masalmani ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Outcomes ◽

Southeast Asian ◽

Case Definition ◽

Etiologic Agent ◽

Cns Infection ◽

Viral Etiology ◽

Varicella Zoster ◽

Cns Infections

Abstract Background Viral central nervous system (CNS) infections are common causes of morbidity and mortality globally. There are no existing data about viral CNS infections in Gulf Cooperation Council countries. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcomes of viral central nerveous system infection in patients in Qatar. Methods We retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at any of the 7 hospitals in the Hamad Medical Corporation. We included those with an abnormal CSF findings and excluded those with missing medical records, no clinical evidence of CNS infection and those with proven bacterial infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, patients were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology. Results Among 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. The most common presenting signs and symptoms are listed in the table. Persons of Southeast Asian origin accounted for 39.6% of all infections. A definitive virologic etiologic agent was found in 38%, with enterovirus being the most common (44.3%) followed by Epstein–Barr virus (31%) and varicella-zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3 ± 5.2 days), 38% received vancomycin (mean duration 2.7 ± 5.4 days) and 38% received at least one other antibiotic. Conclusion Viral etiology is common among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections. Disclosures A. Butt, Merck: Investigator, Grant recipient

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz324 ◽

2019 ◽

Vol 6 (7) ◽

Cited By ~ 2

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.

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Molecular Epidemiology of Enterovirus in Children with Central Nervous System Infections

Viruses ◽

10.3390/v13010100 ◽

2021 ◽

Vol 13 (1) ◽

pp. 100

Author(s):

Lamprini Posnakoglou ◽

Elizabeth-Barbara Tatsi ◽

Panagiota Chatzichristou ◽

Tania Siahanidou ◽

Christina Kanaka-Gantenbein ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Molecular Epidemiology ◽

Seasonal Distribution ◽

Cns Infection ◽

Pediatric Hospital ◽

Central Nervous System Infections ◽

Cns Infections ◽

Epidemiology Data ◽

Of Greece

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0–16 years) with suspected meningitis–encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray® ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1–60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates.

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342. Clinical Utility of a Next Generation Sequencing Test for Pathogen Detection in Pediatric Central Nervous System Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.537 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S241-S241

Author(s):

Nanda Ramchandar ◽

Jennifer Foley ◽

Claudia Enriquez ◽

Stephanie Osborne ◽

Antonio Arrieta ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Next Generation Sequencing ◽

Standard Care ◽

Cns Infection ◽

Next Generation ◽

Diagnostic Modality ◽

Cns Infections ◽

Pcr Multiplex ◽

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. However, standard care testing by culture, serology, and PCR is often unable to identify a pathogen. We examined use of next generation sequencing (NGS) of cerebrospinal fluid (CSF) in detecting an organism in children with CNS infections. Methods We prospectively enrolled children with CSF pleocytosis and suspected CNS infection admitted to 3 tertiary pediatric hospitals. After standard care testing had been performed, the remaining CSF was submitted for analysis by NGS. Results We enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 24 (34.3%) subjects by any diagnostic modality. NGS of the CSF samples identified a pathogen in 20 (28.6%) subjects. False positive results by NGS were identified in 2 patients. There were no cases in which NGS alone identified a pathogen. In 4 cases, a putative organism was recovered by standard care testing of the CSF, but not by CSF NGS. CSF culture recovered a putative organism in 12 cases (12.1%). A CSF PCR multiplex panel was utilized for 51 subjects. An organism was detected in 15 of these (29.4%). Using a reference composite of standard care testing, we determined the sensitivity and specificity of CSF NGS to be 83.3% (95% CI, 62.6–95.3%) and 91.3% (95% CI, 79.2–97.6%) respectively. Conclusion Sequencing of CSF has the potential to rapidly and comprehensively identify infection with a single test. Further studies are needed to determine the optimal use of NGS for diagnosis of CNS infections. Disclosures All Authors: No reported disclosures

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Suspected Central Nervous System Infections in HIV-Infected Adults

Frontiers in Neurology ◽

10.3389/fneur.2021.741884 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fereshte Sheybani ◽

Diederik van de Beek ◽

Matthijs C. Brouwer

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Leukocyte Count ◽

Final Diagnosis ◽

Blood Parameters ◽

Cns Infection ◽

Hiv Encephalitis ◽

Cd4 Counts ◽

Varicella Zoster ◽

Cns Infections

Objectives: To study the differential diagnosis of HIV-infected patients with suspected central nervous system (CNS) infections and the association of CD4 counts with the final diagnosis.Methods: We analyzed HIV-infected patients from a prospective cohort study on the diagnostic accuracy of clinical and laboratory characteristics in adults with suspected CNS infections in an academic hospital in Amsterdam, the Netherlands, who underwent cerebrospinal fluid (CSF) examination.Results: Thirty-four (9.4%) out of 363 patients with suspected CNS infections were HIV-positive of whom 18 (53%) were diagnosed to have CNS infection, with median CD4 counts of 255 cells/μl. The spectrum of CNS infections consisted of progressive multifocal leukoencephalopathy in three patients (17%); cryptococcal meningoencephalitis, toxoplasma encephalitis, angiostrongylus eosinophilic meningitis, and HIV encephalitis each in two (11%); and cytomegalovirus encephalitis, neurosyphilis, tuberculous meningoencephalitis, histoplasma encephalitis, and varicella-zoster virus meningitis each in one (6%). Clinical characteristics and blood parameters did not differ between HIV-infected patients with CNS infections and other diagnoses. The best predictor for CNS infections was the CSF leukocyte count (AUC = 0.77, 95 CI% 0.61–0.94). The diagnosis of CNS infection was not associated with the CD4 count (median 205 vs. 370, p = 0.21). Two patients (11%) with CNS infections died and two (11%) had neurological sequelae.Conclusions: Half of the patients with suspected CNS infections are diagnosed with a CNS infection, and this was not related to CD4 counts. The best predictor for CNS infections was the CSF leukocyte count.

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