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Contamine M, Ader F, Lepiller Q, Martha B, Cagnon-Chapalain J, Leturnier P, Frober E, Bouiller K, Binquet C, Auvray C, Piroth L, Blot M. Acyclovir treatment of varicella-zoster virus meningeal infections and acute kidney injury: a multicentre case series study. Infect Dis (Lond) 2024; 56:842-850. [PMID: 38822453 DOI: 10.1080/23744235.2024.2355989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 04/12/2024] [Accepted: 05/12/2024] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement. METHODS Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations). RESULTS 154 patients were included (median age 66 (interquartile range 43-77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis. CONCLUSIONS Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.
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Affiliation(s)
- Myriam Contamine
- Department of Infectious Diseases, Dijon-Bourgogne University Hospital, Dijon, France
| | - Florence Ader
- Department of Infectious Diseases, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Quentin Lepiller
- Laboratory of virology, Besançon University Hospital, Besançon, France
| | - Benoit Martha
- Department of Infectious Diseases, William Morey Hospital, Chalon sur Saône, France
| | | | - Paul Leturnier
- Infectious and Tropical Diseases Unit, Cayenne General Hospital, Cayenne, French Guiana
- Cayenne General Hospital, INSERM, Cayenne, French Guiana
| | - Emilie Frober
- Laboratory of virology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Kevin Bouiller
- Department of infectious and tropical diseases, Université de Franche-Comté, CHU Besançon, UMR-CNRS 6249 Chrono-environnement, Besançon, France
| | - Christine Binquet
- CHU Dijon-Bourgogne, INSERM, Université de Bourgogne, CIC 1432, Module Épidémiologie Clinique, Dijon, France
- LabEx LipSTIC, University of Burgundy, Dijon, France
- Lipness Team, INSERM Research Centre LNC-UMR1231 and LabEx LipSTIC, University of Burgundy, Dijon, France
| | - Christelle Auvray
- Laboratory of virology, Dijon-Bourgogne University Hospital, Dijon, France
| | - Lionel Piroth
- Department of Infectious Diseases, Dijon-Bourgogne University Hospital, Dijon, France
- CHU Dijon-Bourgogne, INSERM, Université de Bourgogne, CIC 1432, Module Épidémiologie Clinique, Dijon, France
- LabEx LipSTIC, University of Burgundy, Dijon, France
| | - Mathieu Blot
- Department of Infectious Diseases, Dijon-Bourgogne University Hospital, Dijon, France
- CHU Dijon-Bourgogne, INSERM, Université de Bourgogne, CIC 1432, Module Épidémiologie Clinique, Dijon, France
- LabEx LipSTIC, University of Burgundy, Dijon, France
- Lipness Team, INSERM Research Centre LNC-UMR1231 and LabEx LipSTIC, University of Burgundy, Dijon, France
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Miry L, De Mesmay M, Quirins M, Wemmert C, Khemili M, Engrand N. Case report: Varicella-zoster virus encephalitis a new type of "ICU-acquired infection"? Heliyon 2024; 10:e34629. [PMID: 39130407 PMCID: PMC11315075 DOI: 10.1016/j.heliyon.2024.e34629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 07/12/2024] [Accepted: 07/12/2024] [Indexed: 08/13/2024] Open
Abstract
Purpose Varicella-zoster virus (VZV) can cause a wide range of neurological complications, including meningoencephalitis, upon reactivation. The objective of this report is to alert physicians of the possibility of VZV recurrence with meningoencephalitis occurring during hospitalization in an intensive care unit (ICU) setting. Material and methods Clinical observation of one patient. Case report A 65 years old man was admitted to the ICU for subarachnoid hemorrhage. Although the initial treatment plan proved successful, the patient experienced numerous, mainly septic, complications. After stabilization, neurological impairment was observed with spontaneous eye opening without contact and no motor response, apart from sedation. Cerebrospinal fluid (CSF) PCR assay was positive for VZV. Intravenous acyclovir was administered for 14 days. Neurological status gradually improved with the patient showing eye and mouth opening on request as well as recovery of basic speech with one-word responses. Quantitative PCR assays showed significant decrease of VZV. EEG improved after treatment to show clear reactivity, but the abnormalities at baseline were non-specific of VZV meningoencephalitis. No new focal lesion was identified on MRI that could be linked to VZV meningoencephalitis. The patient recovered from VZV meningoencephalitis, but he finally died 44 days later, following cardiac arrest, with no reactivation of VZV infection. Conclusion VZV meningoencephalitis may occur during hospitalization, especially during prolonged ICU stay which may be due to reactivation associated with sepsis-induced immunosuppression. It might be underestimated as MRI and EEG seem poorly contributive to the diagnosis, so CSF PCR analysis is the cornerstone exploration.
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Affiliation(s)
- Loïc Miry
- Neuro-Intensive Care Unit, Rothschild Foundation Hospital, 29 Rue Manin, 75019 Paris, France
| | - Marine De Mesmay
- Neuro-Intensive Care Unit, Rothschild Foundation Hospital, 29 Rue Manin, 75019 Paris, France
| | - Marion Quirins
- Department of Neurology Rothschild Foundation Hospital, 29 Rue Manin, 75019 Paris, France
| | - Charlotte Wemmert
- Department of Medicine, Rothschild Foundation Hospital, 29 Rue Manin, 75019 Paris, France
| | - Mohamed Khemili
- Neuro-Intensive Care Unit, Rothschild Foundation Hospital, 29 Rue Manin, 75019 Paris, France
| | - Nicolas Engrand
- Neuro-Intensive Care Unit, Rothschild Foundation Hospital, 29 Rue Manin, 75019 Paris, France
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Poussier L, Mailles A, Tattevin P, Stahl JP, Fillâtre P. Characteristics, management and outcome of Herpes Simplex and Varicella-Zoster virus encephalitis: a multicentre prospective cohort study. Clin Microbiol Infect 2024; 30:917-923. [PMID: 38527616 DOI: 10.1016/j.cmi.2024.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 03/03/2024] [Accepted: 03/13/2024] [Indexed: 03/27/2024]
Abstract
OBJECTIVE To characterize differences between Herpes Simplex virus encephalitis and Varicella-Zoster virus encephalitis (HSVE and VZVE) and other aetiologies of infectious encephalitis (IE), and to investigate the impact of time-to-aciclovir (ACV) start, ACV dose and duration on outcome. METHODS We compared 132 HSVE, 65 VZVE and 297 other IE enrolled in a prospective cohort (ENCEIF). We estimated associations between time-to-ACV start, dose or duration and outcome through adjusted odds ratio (aOR) using logistic regression analysis. RESULTS Prevalence of immunodepression differed among aetiologies: 15/65 (23%) for VZVE, 13/132 (10%) for HSVE and 30/297 (10%) for other IE (p <0.05), as was presence of seizure at admission: 27/132 (20%) for HSVE, 4/65 (6%) for VZVE and 43/297 (14%) for other IE (p <0.05). Poor outcome at hospital discharge (Glasgow outcome scale ≤3) differed among the three groups: 40/127 (31%) for HSVE, 12/65 (18%) for VZVE and 38/290 (13%) for other IE (p <0.05). Time-to-ACV start was associated with outcome in HSVE (aOR 3.61 [1.25-10.40]), but not in VZVE (aOR 0.84 [0.18-3.85]). Increased ACV dose was not associated with outcome among HSVE (aOR 1.25 [0.44-3.64]) nor VZVE (aOR 1.16 [0.24-5.73]). DISCUSSION HSVE and VZVE are distinct in clinical presentation, outcome and prognostic factors. The impact of early ACV initiation was more apparent for HSVE than for VZVE; however, this could be because of VZVE's smaller sample size and lower outcome rate leading to low statistical power or because of potential distinct IE pathophysiology.
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Affiliation(s)
- Léa Poussier
- Infectious Diseases and Intensive Care Unit, CHU Pontchaillou, Rennes, France; INSERM, CIC 1414, Rennes, France
| | | | - Pierre Tattevin
- Infectious Diseases and Intensive Care Unit, CHU Pontchaillou, Rennes, France; INSERM, CIC 1414, Rennes, France
| | - Jean-Paul Stahl
- Infectious Diseases Department, University Grenoble Alpes, Grenoble, France
| | - Pierre Fillâtre
- INSERM, CIC 1414, Rennes, France; Intensive Care Unit, Yves Le Foll Hospital, Saint Brieuc, France.
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Sun M, Manson ML, Guo T, de Lange ECM. CNS Viral Infections-What to Consider for Improving Drug Treatment: A Plea for Using Mathematical Modeling Approaches. CNS Drugs 2024; 38:349-373. [PMID: 38580795 PMCID: PMC11026214 DOI: 10.1007/s40263-024-01082-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/10/2024] [Indexed: 04/07/2024]
Abstract
Neurotropic viruses may cause meningitis, myelitis, encephalitis, or meningoencephalitis. These inflammatory conditions of the central nervous system (CNS) may have serious and devastating consequences if not treated adequately. In this review, we first summarize how neurotropic viruses can enter the CNS by (1) crossing the blood-brain barrier or blood-cerebrospinal fluid barrier; (2) invading the nose via the olfactory route; or (3) invading the peripheral nervous system. Neurotropic viruses may then enter the intracellular space of brain cells via endocytosis and/or membrane fusion. Antiviral drugs are currently used for different viral CNS infections, even though their use and dosing regimens within the CNS, with the exception of acyclovir, are minimally supported by clinical evidence. We therefore provide considerations to optimize drug treatment(s) for these neurotropic viruses. Antiviral drugs should cross the blood-brain barrier/blood cerebrospinal fluid barrier and pass the brain cellular membrane to inhibit these viruses inside the brain cells. Some antiviral drugs may also require intracellular conversion into their active metabolite(s). This illustrates the need to better understand these mechanisms because these processes dictate drug exposure within the CNS that ultimately determine the success of antiviral drugs for CNS infections. Finally, we discuss mathematical model-based approaches for optimizing antiviral treatments. Thereby emphasizing the potential of CNS physiologically based pharmacokinetic models because direct measurement of brain intracellular exposure in living humans faces ethical restrictions. Existing physiologically based pharmacokinetic models combined with in vitro pharmacokinetic/pharmacodynamic information can be used to predict drug exposure and evaluate efficacy of antiviral drugs within the CNS, to ultimately optimize the treatments of CNS viral infections.
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Affiliation(s)
- Ming Sun
- Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands
| | - Martijn L Manson
- Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands
| | - Tingjie Guo
- Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands
| | - Elizabeth C M de Lange
- Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
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Erba A, Franzeck FC, Hinic V, Egli A, Osthoff M. Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule. Front Med (Lausanne) 2024; 11:1351903. [PMID: 38695026 PMCID: PMC11061443 DOI: 10.3389/fmed.2024.1351903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 04/05/2024] [Indexed: 05/04/2024] Open
Abstract
Background The Biofire® FilmArray® Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule. Materials Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests. Results 1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), Streptococcus pneumoniae (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria. Conclusion The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.
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Affiliation(s)
- Andrea Erba
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Fabian C. Franzeck
- Clinical Data Warehouse, Research and Analytics Services, University Hospital Basel, Basel, Switzerland
| | - Vladimira Hinic
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
- Division of Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
| | - Adrian Egli
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
- Division of Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland
| | - Michael Osthoff
- Department of Internal Medicine, University Hospital Basel, Basel, Switzerland
- Department of Internal Medicine, Cantonal Hospital Winterthur, Winterthur, Switzerland
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Malherbe J, Godard P, Lacherade JC, Coirier V, Argaud L, Hyvernat H, Schneider F, Charpentier J, Wallet F, Pocquet J, Plantefeve G, Quenot JP, Bay P, Delbove A, Georges H, Urbina T, Schnell D, Le Moal C, Stanowski M, Muris C, Jonas M, Sauneuf B, Lesieur O, Lhermitte A, Calvet L, Gueguen I, du Cheyron D. Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study. Ann Intensive Care 2024; 14:44. [PMID: 38548917 PMCID: PMC10978565 DOI: 10.1186/s13613-024-01270-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/23/2024] [Indexed: 04/01/2024] Open
Abstract
BACKGROUND Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. RESULTS One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001). CONCLUSION Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.
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Affiliation(s)
- Jolan Malherbe
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Médecine Intensive - Réanimation, Caen, 14000, France.
| | - Pierre Godard
- Service de Médecine Intensive - Réanimation, CHU Bordeaux site Pellegrin, Bordeaux, France
| | | | - Valentin Coirier
- Service de Médecine Intensive - Réanimation, CHU de Rennes, Rennes, 35000, France
| | - Laurent Argaud
- Service de Médecine Intensive - Réanimation, Hôpital Edouard Herriot, Hospices civils de Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Est, Lyon, France
| | - Hervé Hyvernat
- Service de Médecine Intensive - Réanimation, Université Côte d'Azur (UCA), CHU de Nice, 151 route Saint Antoine de Ginestière, Nice, 06200, France
| | - Francis Schneider
- Médecine Intensive - Réanimation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg et Unistra, Strasbourg, France
| | - Julien Charpentier
- Service de Médecine Intensive - Réanimation, Centre-Université Paris Cité, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, 75014, France
| | - Florent Wallet
- Médecine Intensive - Réanimation, CHU Lyon Sud, Pierre Benite, France
- RESHAPE Research on healthcare performance, U1290, Université Claude Bernard Lyon 1, Lyon, France
| | | | | | - Jean-Pierre Quenot
- Department of Intensive Care, Burgundy University Hospital, Dijon, France
| | - Pierre Bay
- Service de Médecine Intensive - Réanimation, AP-HP Assistance Publique Hôpitaux de Paris, Hôpitaux universitaires Henri Mondor, DMU Médecine, Créteil, 94010, France
- UPEC Université Paris-Est Créteil, INSERM, Unité U955, Equipe 18, Créteil, 94010, France
| | - Agathe Delbove
- Service de réanimation polyvalente, CHBA Vannes, Vannes, France
| | - Hugues Georges
- Service de réanimation polyvalente, Centre hospitalier de Tourcoing, Tourcoing, 59200, France
| | - Tomas Urbina
- Service de Médecine Intensive - Réanimation, Hôpital Saint-Antoine, Assistance Publique- Hôpitaux de Paris, Paris, 75012, France
| | - David Schnell
- Réanimation Polyvalente et USC, CH Angoulême, Angoulême Cedex 9, Angoulême, 19959, France
| | - Charlène Le Moal
- Service Réanimation/USC, Centre Hospitalier du Mans, Le Mans, 72037, France
| | | | - Corentin Muris
- Université de Poitiers, CHU de Poitiers, Médecine intensive Réanimation, 2 rue de la miletrie, Poitiers, 86000, France
| | - Maud Jonas
- Service Médecine Intensive - Réanimation/USC, Centre hospitalier de Saint-Nazaire, Saint-Nazaire, 44600, France
| | - Bertrand Sauneuf
- Service de Réanimation polyvalente, Centre Hospitalier Public du Cotentin, Cherbourg en Cotentin, 50100, France
| | - Olivier Lesieur
- Centre Hospitalier Saint-Louis, Réanimation polyvalente, La Rochelle, 17019, France
| | - Amaury Lhermitte
- Hôpital Universitaire Félix Guyon, Réanimation polyvalente, Allée des Topazes, Saint-Denis, La Réunion, 97400, France
| | - Laure Calvet
- Service de Médecine Intensive et Réanimation, CHU de Clermont-Ferrand, Clermont- Ferrand, France
| | - Ines Gueguen
- Service de réanimation médicale, CHRU de Lille, Lille, France
| | - Damien du Cheyron
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Médecine Intensive - Réanimation, Caen, 14000, France
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Landré S, Ader F, Epaulard O, Tattevin P, Stahl JP, Mailles A. Encephalitis in HIV-negative immunodeficient patients: a prospective multicentre study, France, 2016 to 2019. Euro Surveill 2024; 29:2300046. [PMID: 38333938 PMCID: PMC10853978 DOI: 10.2807/1560-7917.es.2024.29.6.2300046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 06/01/2023] [Indexed: 02/10/2024] Open
Abstract
BackgroundData on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.AimWe aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.MethodsPatients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson's chi-squared test and Student's t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.ResultsID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70-6.85).ConclusionsVaricella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.
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Affiliation(s)
- Sophie Landré
- University Claude Bernard Lyon 1, Hospices Civils de Lyon, Infectious disease department, Lyon, France
| | - Florence Ader
- University Claude Bernard Lyon 1, Hospices Civils de Lyon, Infectious disease department, Lyon, France
- Centre International de Recherche en Infectiologie (CIRI), Inserm 1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Univ Lyon, France
| | - Olivier Epaulard
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland
- University Grenoble Alpes, Infectious diseases department, Grenoble, France
| | - Pierre Tattevin
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland
- Infectious diseases department, CHU Pontchaillou, Rennes, France
| | - Jean Paul Stahl
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland
- University Grenoble Alpes, Infectious diseases department, Grenoble, France
| | - Alexandra Mailles
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland
- Santé Publique France, Saint-Maurice, France
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Abbuehl LS, Branca M, Ungureanu A, Federspiel A, Leib SL, Bassetti CLA, Hakim A, Dietmann A. Magnetic resonance imaging in acute meningoencephalitis of viral and unknown origin: frequent findings and prognostic potential. Front Neurol 2024; 15:1359437. [PMID: 38299018 PMCID: PMC10829495 DOI: 10.3389/fneur.2024.1359437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 01/05/2024] [Indexed: 02/02/2024] Open
Abstract
Background Magnetic resonance imaging (MRI) findings in meningoencephalitis have mainly been described in terms of their diagnostic value rather than their prognostic potential, except for herpes simplex virus (HSV) encephalitis. The aims of our study were to describe frequency and anatomic locations of MRI abnormalities specific to limbic, circadian and motor systems in a cohort of meningoencephalitis patients, as well as to investigate the prognostic value of these MRI findings. Methods A secondary, selective analysis of a retrospective database including all meningitis, meningoencephalitis and encephalitis cases treated between 2016 and 2018 in the University hospital of Bern, Switzerland was performed. Patients with meningitis of any cause, bacterial or autoimmune causes of encephalitis were excluded. Results MRI scans and clinical data from 129 meningoencephalitis cases found that the most frequent causes were tick-borne encephalitis (TBE, 42%), unknown pathogens (40%), VZV (7%), and HSV1 (5%). At discharge, median modified Rankin Score (mRS) was 3 (interquartile range, IQR, 1), 88% of patients had persisting signs and symptoms. After a median of 17 months, median Glasgow Outcome Score (GOS) was 5 (IQR 1), 39% of patients still had residual signs or symptoms. All patients with HSV, 27% with TBE and 31% of those with meningoencephalitis of unknown etiology had fluid-attenuated inversion recovery (FLAIR) and to a lesser extent diffusion-weighted imaging (DWI) lesions in their initial MRI, with highly overlapping anatomical distribution. In one fifth of TBE patients the limbic system was affected. Worse outcome was associated with presence of DWI and/or FLAIR lesions and lower normalized apparent diffusion coefficient (ADC) signal intensities. Conclusion Presence of FLAIR lesions, restricted diffusion as well as the extent of ADC hypointensity in initial MRI are parameters which might be of prognostic value regarding the longterm clinical outcome for patients with meningoencephalitis of viral and of unknown origin. Although not described before, affection of limbic structures by TBE is possible as shown by our results: A substantial proportion of our TBE patients had FLAIR signal abnormalities in these regions.
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Affiliation(s)
- Lena S. Abbuehl
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | - Anamaria Ungureanu
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andrea Federspiel
- Support Center for Advanced Neuroimaging Translational Imaging Center (sitem-insel), Institute for Diagnostic and Interventional Neuroradiology, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Stephen L. Leib
- Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Claudio L. A. Bassetti
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Arsany Hakim
- Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Anelia Dietmann
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Bharucha T, Brown RL, Marcoci C, Benjamin L, Hoskote C, McNamara P, Spillane J, Zandi MS, Manji H. The Queen Square Encephalitis Multidisciplinary Team Meeting - experience over three years, pre and post the COVID-19 pandemic. J Neurol Sci 2023; 453:120771. [PMID: 37793287 PMCID: PMC10951958 DOI: 10.1016/j.jns.2023.120771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 08/14/2023] [Accepted: 08/19/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years. METHODS A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses. RESULTS Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management. CONCLUSIONS Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base.
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Affiliation(s)
- Tehmina Bharucha
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
| | - Rachel L Brown
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; University College London, Queen Square Institute of Neurology, London WC1N 3BG, UK; UCL Institute of Immunity and Transplantation, London NW3 2PP, UK
| | - Cristina Marcoci
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
| | - Laura Benjamin
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; UCL Laboratory of Molecular and Cell Biology, London WC1E 6BT, UK
| | - Chandrashekar Hoskote
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK
| | - Patricia McNamara
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
| | - Jennifer Spillane
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
| | - Michael S Zandi
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; University College London, Queen Square Institute of Neurology, London WC1N 3BG, UK
| | - Hadi Manji
- National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; University College London, Queen Square Institute of Neurology, London WC1N 3BG, UK.
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10
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Thy M, de Montmollin E, Bouadma L, Timsit JF, Sonneville R. Severe meningoencephalitis: epidemiology and outcomes. Curr Opin Crit Care 2023; 29:415-422. [PMID: 37641514 DOI: 10.1097/mcc.0000000000001087] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
PURPOSE OF REVIEW This article aims to provide an updated review on the epidemiology and outcomes of severe meningoencephalitis. RECENT FINDINGS Meningoencephalitis is a critical medical condition characterized by inflammation in both the meninges and brain parenchyma. Bacterial, viral, or fungal infections are common causes, although noninfectious factors, such as autoimmune causes, can also contribute. In patients requiring intensive care, meningoencephalitis is associated with a severe prognosis, including mortality rates ranging from 11 to 25% and functional disability in 15-25% of survivors. Recent multicenter studies have identified several parameters linked to poor outcomes, including older age, immunocompromised status, focal neurologic signs, abnormal brain imaging, and delayed administration of antimicrobials. The use of new multiplex PCR techniques for diagnosis has generated debate based on recent data. Investigation is still needed to determine the effectiveness of adjunctive therapies, including seizure prophylaxis, and adjunctive steroids for nonbacterial causes. SUMMARY Recent multicenter studies have enhanced our understanding of the current epidemiology and outcomes of severe meningoencephalitis in adult patients.
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Affiliation(s)
- Michael Thy
- Department of Intensive Care Medicine
- Department of Infectious and Tropical Diseases, AP-HP, Bichat Hospital
- EA 7323 - Pharmacology and Therapeutic Evaluation in Children and Pregnant Women
| | - Etienne de Montmollin
- Department of Intensive Care Medicine
- INSERM UMR1137, IAME, Université de Paris Cité, Paris, France
| | - Lila Bouadma
- Department of Intensive Care Medicine
- INSERM UMR1137, IAME, Université de Paris Cité, Paris, France
| | - Jean-François Timsit
- Department of Intensive Care Medicine
- INSERM UMR1137, IAME, Université de Paris Cité, Paris, France
| | - Romain Sonneville
- Department of Intensive Care Medicine
- INSERM UMR1137, IAME, Université de Paris Cité, Paris, France
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11
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Bloch KC, Glaser C, Gaston D, Venkatesan A. State of the Art: Acute Encephalitis. Clin Infect Dis 2023; 77:e14-e33. [PMID: 37485952 DOI: 10.1093/cid/ciad306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Indexed: 07/25/2023] Open
Abstract
Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.
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Affiliation(s)
- Karen C Bloch
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Carol Glaser
- California Department of Public Health, Richmond, California, USA
| | - David Gaston
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Arun Venkatesan
- Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA
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12
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Reimer-Mcatee M, Ramirez D, Mcatee C, Granillo A, Hasbun R. Encephalitis in HIV-infected adults in the antiretroviral therapy era. J Neurol 2023; 270:3914-3933. [PMID: 37115358 PMCID: PMC11332430 DOI: 10.1007/s00415-023-11735-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/18/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023]
Abstract
INTRODUCTION Encephalitis presents with high morbidity and mortality in both HIV-infected and HIV-negative patients. There are currently no studies comparing HIV-infected and HIV-negative patients admitted to the hospital with acute encephalitis. METHODS We conducted a multicenter, retrospective study of adults admitted to the hospital with a diagnosis of encephalitis in Houston, Texas between 2005 and 2020. We describe the clinical manifestations, etiology, and outcomes of these patients with a focus on those infected with HIV. RESULTS We identified 260 patients with encephalitis, 40 of whom were infected with HIV. Viral etiology was identified in 18 of the 40 HIV-infected patients (45.0%); bacterial in 9 (22.5%); parasitic in 5 (12.5%); fungal in 3 (7.5%); immune-mediated in 2 (5.0%). Eleven cases had unclear etiology (27.5%). More than one disease process was identified in 12 (30.0%) patients. HIV-infected persons were more likely to have neurosyphilis (8/40 vs. 1/220; OR 55; 95%CI 6.6-450), CMV encephalitis [5/18 vs. 1/30; OR 11.2 (1.18-105)], or VZV encephalitis (8/21 vs. 10/89; OR 4.82; 1.62-14.6) compared to the HIV-negative patients. Inpatient mortality was similar in the HIV-infected and HIV-negative patients, 15.0% vs 9.5% [p = 0.4, OR 1.67 (0.63-4.44)], but one-year mortality was higher for the HIV-infected patients, 31.3% vs 16.0% [p = 0.04, OR 2.40 (1.02-5.55)]. CONCLUSION This large, multicenter study shows that HIV-infected patients with encephalitis have a distinct pattern of disease when compared with HIV-negative patients, and that this population has nearly twice the odds of mortality in the year following hospitalization.
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Affiliation(s)
- Melissa Reimer-Mcatee
- Section of Infectious Diseases, UT Health McGovern Medical School, Houston, TX, USA.
- Institute for Global Health and Infectious Diseases, University of North Carolina UNC Project Malawi, Lilongwe, Malawi.
- Washington University in St. Louis, ACHIEVE Fogarty Global Health Program, Lilongwe, Malawi.
| | - Denisse Ramirez
- Section of Infectious Diseases, UT Health McGovern Medical School, Houston, TX, USA
| | | | - Alejandro Granillo
- Section of Infectious Diseases, UT Health McGovern Medical School, Houston, TX, USA
| | - Rodrigo Hasbun
- Section of Infectious Diseases, UT Health McGovern Medical School, Houston, TX, USA.
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13
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Cottu A, Kante A, Megherbi A, Lhomme S, Maisonneuve L, Santoli F. A frantic confusion: beyond rabies and anti-N-methyl-D-aspartate encephalitis. J Neurovirol 2023; 29:358-363. [PMID: 37171751 DOI: 10.1007/s13365-023-01146-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/12/2023] [Accepted: 04/27/2023] [Indexed: 05/13/2023]
Abstract
Hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. In rare cases, HEV may generate neurologic lesions such as neuralgic amyotrophy, Guillain-Barré syndrome, and meningoencephalitis. Thirteen cases of HEV meningoencephalitis have been reported over 20 years. The clinical landscape varied from mild symptoms to coma and seizures. Most of patients were immunocompetent adults and spontaneously recovered. We report here the case of a 44-year-old immunocompetent adult with HEV meningoencephalitis presenting with aggressiveness and then coma. The evolution was spontaneously favorable without any specific treatment. This clinical case aims to draw attention on this emerging and probably under-recognized cause of meningoencephalitis.
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Affiliation(s)
- Adrien Cottu
- Service de Réanimation Médicale, Centre Hospitalo-Universitaire Robert Ballanger, Aulnay-Sous-Bois, France.
- Université Pierre et Marie Curie, Sorbonne Universités, Paris 6, Paris, France.
| | - Aïcha Kante
- Service de Réanimation Médicale, Centre Hospitalo-Universitaire Robert Ballanger, Aulnay-Sous-Bois, France
- Université Pierre et Marie Curie, Sorbonne Universités, Paris 6, Paris, France
| | - Alexandre Megherbi
- Service de Réanimation Médicale, Centre Hospitalo-Universitaire Robert Ballanger, Aulnay-Sous-Bois, France
- Université Pierre et Marie Curie, Sorbonne Universités, Paris 6, Paris, France
| | - Sébastien Lhomme
- Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31300, Toulouse, France
- Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR1291-CNRS UMR5051, INSERM, 31300, Toulouse, France
- Université Toulouse III Paul-Sabatier, 31062, Toulouse, France
| | - Lydia Maisonneuve
- Service de Biologie Médicale, Centre Hospitalo-Universitaire Robert Ballanger, Aulnay-Sous-Bois, France
| | - Francesco Santoli
- Service de Réanimation Médicale, Centre Hospitalo-Universitaire Robert Ballanger, Aulnay-Sous-Bois, France
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Fillatre P, Mailles A, Stahl JP, Tattevin P. Characteristics, management, and outcomes of patients with infectious encephalitis requiring intensive care: A prospective multicentre observational study. J Crit Care 2023; 77:154300. [PMID: 37207520 DOI: 10.1016/j.jcrc.2023.154300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 01/23/2023] [Accepted: 03/30/2023] [Indexed: 05/21/2023]
Abstract
PURPOSE Infectious encephalitis (IE) is a severe disease which requires intensive care unit (ICU) admission in up to 50% of cases. We aimed to describe characteristics, management and outcomes of IE patients who required ICU admission. MATERIALS AND METHODS Ancillary study focusing on patients with ICU admission within the ENCEIF cohort, a French prospective observational multicentre study. The primary criteria for outcome was the functional status at hospital discharge, categorized using the Glasgow outcome scale (GOS). Logistic regression model was used to identify risk factors for poor outcome, defined as a GOS ≤ 3. RESULTS We enrolled 198 ICU patients with IE. HSV was the primary cause (n = 72, 36% of all IE, 53% of IE with microbiological documentation). Fifty-two patients (26%) had poor outcome at hospital discharge, including 22 deaths (11%). Immunodeficiency, supratentorial focal signs on admission, lower cerebrospinal fluid (CSF) white cells count (<75/mm3), abnormal brain imaging, and time from symptoms onset to acyclovir start >2 days were independent predictors of poor outcome. CONCLUSION HSV is the primary cause of IE requiring ICU admission. IE patients admitted in ICU have a poor prognosis with 11% of in-hospital mortality and 15% of severe disabilities in survivors at discharge.
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Affiliation(s)
- Pierre Fillatre
- Intensive care unit, Centre Hospitalier Yves Le Foll, Saint Brieuc, France; INSERM, CIC 1414, Rennes, France.
| | | | - Jean Paul Stahl
- University Grenoble Alpes, Infectious diseases department, Grenoble, France
| | - Pierre Tattevin
- INSERM, CIC 1414, Rennes, France; Infectious diseases department, CHU Ponchaillou, Rennes, France
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15
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Sonneville R, de Montmollin E, Contou D, Ferrer R, Gurjar M, Klouche K, Sarton B, Demeret S, Bailly P, da Silva D, Escudier E, Le Guennec L, Chabanne R, Argaud L, Ben Hadj Salem O, Thyrault M, Frerou A, Louis G, De Pascale G, Horn J, Helbok R, Geri G, Bruneel F, Martin-Loeches I, Taccone FS, De Waele JJ, Ruckly S, Staiquly Q, Citerio G, Timsit JF. Clinical features, etiologies, and outcomes in adult patients with meningoencephalitis requiring intensive care (EURECA): an international prospective multicenter cohort study. Intensive Care Med 2023; 49:517-529. [PMID: 37022378 DOI: 10.1007/s00134-023-07032-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 03/08/2023] [Indexed: 04/07/2023]
Abstract
PURPOSE We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. METHODS We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. RESULTS Among 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78) and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective. CONCLUSION Meningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.
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Affiliation(s)
- Romain Sonneville
- Université Paris Cité, INSERM UMR 1137, 75018, Paris, France.
- APHP, Department of Intensive Care Medicine, Bichat-Claude Bernard University Hospital, 75018, Paris, France.
- Service de Médecine Intensive-Réanimation, Hôpital Bichat-Claude Bernard, 46 Rue Henri Huchard, 75877, Paris Cedex, France.
| | - Etienne de Montmollin
- Université Paris Cité, INSERM UMR 1137, 75018, Paris, France
- APHP, Department of Intensive Care Medicine, Bichat-Claude Bernard University Hospital, 75018, Paris, France
| | - Damien Contou
- Department of Intensive Care Medicine, Victor Dupouy Hospital, Argenteuil, France
| | - Ricard Ferrer
- Department of Intensive Care Medicine, Val d'Hebron University Hospital, Barcelona, Spain
| | - Mohan Gurjar
- Department of Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India
| | - Kada Klouche
- Department of Intensive Care Medicine, Montpellier University Hospital, Montpellier, France
| | - Benjamine Sarton
- Department of Intensive Care Medicine, Purpan University Hospital, Toulouse, France
| | - Sophie Demeret
- Sorbonne University, AP-HP, Neurology Department, Neurological Intensive Care Unit, Pitié Salpêtrière Hospital, Paris, France
| | - Pierre Bailly
- Department of Intensive Care Medicine, Brest University Hospital, Brest, France
| | - Daniel da Silva
- Department of Intensive Care Medicine, Saint Denis University Hospital, Saint Denis, France
| | - Etienne Escudier
- Department of Intensive Care Medicine, Annecy Hospital, Annecy, France
| | - Loic Le Guennec
- Department of Intensive Care Medicine, La Pitié-Salpêtrière University Hospital, Paris, France
| | - Russel Chabanne
- Department of Anesthesia and Intensive Care Medicine, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Laurent Argaud
- Department of Intensive Care Medicine, Lyon University Hospital, Lyon, France
| | - Omar Ben Hadj Salem
- Department of Intensive Care Medicine, Poissy-Saint Germain Hospital, Poissy, France
| | - Martial Thyrault
- Department of Intensive Care Medicine, Longjumeau hospital, Longjumeau, France
| | - Aurélien Frerou
- Department of Intensive Care Medicine, Pontchaillou Hospital, Rennes, France
| | - Guillaume Louis
- Department of Intensive Care Medicine, Metz Hospital, Metz, France
| | - Gennaro De Pascale
- Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A.Gemelli IRCCS, Rome, Italy
| | - Janneke Horn
- Department of Intensive Care Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Raimund Helbok
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- Department of Neurology, Johannes Kepler University Linz, Linz, Austria
| | - Guillaume Geri
- Department of Intensive Care Medicine, Ambroise Paré University Hospital, Boulogne-Billancourt, France
| | - Fabrice Bruneel
- Department of Intensive Care Medicine, Versailles Hospital, Le Chesnay, France
| | | | - Fabio Silvio Taccone
- Department of Intensive Care Medicine, Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium
| | - Jan J De Waele
- Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium
| | | | | | - Giuseppe Citerio
- School of Medicine and Surgery, University Milano Bicocca, Milan, Italy
- NeuroIntensive Care Unit, Department of Neuroscience, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Jean-François Timsit
- Université Paris Cité, INSERM UMR 1137, 75018, Paris, France
- APHP, Department of Intensive Care Medicine, Bichat-Claude Bernard University Hospital, 75018, Paris, France
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16
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Granillo A, Le Maréchal M, Diaz-Arias L, Probasco J, Venkatesan A, Hasbun R. Development and Validation of a Risk Score to Differentiate Viral and Autoimmune Encephalitis in Adults. Clin Infect Dis 2023; 76:e1294-e1301. [PMID: 36053949 DOI: 10.1093/cid/ciac711] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/10/2022] [Accepted: 08/29/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Encephalitis represents a challenging condition to diagnose and treat. To assist physicians in considering autoimmune encephalitis (AE) sooner, we developed and validated a risk score. METHODS The study was conducted as a retrospective cohort of patients with a diagnosis of definite viral encephalitis (VE) and AE from February 2005 to December 2019. Clinically relevant and statistically significant features between cases of AE and VE were explored in a bivariate logistic regression model and results were used to identify variables for inclusion in the risk score. A multivariable logistic model was used to generate risk score values and predict risk for AE. Results were externally validated. RESULTS A total of 1310 patients were screened. Of the 279 enrolled, 36 patients met criteria for definite AE and 88 criteria for definite VE. Patients with AE compared with VE were more likely to have a subacute to chronic presentation (odds ratio [OR] = 22.36; 95% confidence interval [CI], 2.05-243.7), Charlson comorbidity index <2 (OR = 6.62; 95% CI, 1.05-41.4), psychiatric and/or memory complaints (OR = 203.0; 95% CI, 7.57-5445), and absence of robust inflammation in the cerebrospinal fluid defined as <50 white blood cells/µL and protein <50 mg/dL (OR = 0.06; 95% CI, .005-0.50). Using these 4 variables, patients were classified into 3 risk categories for AE: low (0-1), intermediate (2-3), and high (4). Results were externally validated and the performance of the score achieved an area under the curve of 0.918 (95% CI, .871-.966). DISCUSSION This risk score allows clinicians to estimate the probability of AE in patients presenting with encephalitis and may assist with earlier diagnosis and treatment.
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Affiliation(s)
- Alejandro Granillo
- Department of Infectious Diseases, UT Health McGovern Medical School, Houston, Texas, USA
| | - Marion Le Maréchal
- Johns Hopkins Encephalitis Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Luisa Diaz-Arias
- Johns Hopkins Encephalitis Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - John Probasco
- Johns Hopkins Encephalitis Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Arun Venkatesan
- Johns Hopkins Encephalitis Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Rodrigo Hasbun
- Department of Infectious Diseases, UT Health McGovern Medical School, Houston, Texas, USA.,Department of Internal Medicine, UT Health McGovern Medical School, Houston, Texas, USA
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Debbagh F, Harrar S, Babokh F, Lamrani Hanchi A, Soraa N. The Contribution of Multiplex Polymerase Chain Reaction in the Diagnosis of Central Nervous System Infections in Intensive Care Units. Cureus 2023; 15:e35338. [PMID: 36851943 PMCID: PMC9963464 DOI: 10.7759/cureus.35338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2023] [Indexed: 02/25/2023] Open
Abstract
Introduction The aim of this study was to evaluate the contribution and limits of BioFire® FilmArray® meningitis/encephalitis panel (FA MEP) polymerase chain reaction (PCR) (bioMérieux, Marcy-l'Étoile, France) (product references: LLC RFIT-ASY-0118) coupled with bacterial and fungal culture in the diagnosis of central nervous system infections (CNSIs). Methods This was a retrospective observational study including all patients (adults and children) hospitalized in the intensive care units (ICUs) of a Moroccan university hospital, who benefited from multiplex PCR on a cerebrospinal fluid (CSF) sample. Results A total of 112 PCRs were performed, with a positivity rate of 18%. Bacterial etiology was the most frequent (70%), represented mainly by Streptococcus pneumoniae (45%), followed by viruses (25%), with four isolates of Herpes simplex virus (HSV) 1. On 94 samples, there was an agreement between the culture and PCR results. Their discordance was found in 18 cases, including 16 suspected CNSIs recovered only by PCR and two diagnoses confirmed only by bacterial culture. Conclusion This study revealed the significant impact of multiplex PCR on the early and targeted diagnostic and therapeutic management of infectious meningitis and meningoencephalitis in intensive care unit patients.
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Affiliation(s)
- Fayrouz Debbagh
- Microbiology Laboratory, Faculty of Medicine and Pharmacy, Mohammed VI University Hospital of Marrakech, Cadi Ayyad University, Marrakech, MAR.,Biochemistry-Toxicology Laboratory, Avicenna Military Hospital, Marrakech, MAR
| | - Sara Harrar
- Microbiology Department, Arrazi Hospital, Mohammed VI University Hospital of Marrakech, Marrakech, MAR
| | - Fatima Babokh
- Biology Department/Parasitology and Mycology Laboratory, Faculty of Medicine and Pharmacy, Mohammed VI University Hospital of Marrakech, Cadi Ayyad University, Marrakech, MAR
| | - Asma Lamrani Hanchi
- Microbiology Department, Arrazi Hospital, Mohammed VI University Hospital of Marrakech, Marrakech, MAR
| | - Nabila Soraa
- Microbiology Laboratory, Arrazi Hospital, Mohammed VI University Hospital of Marrakech, Marrakech, MAR
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Si Y, He W, Guo S, Wang X, Tang M, Ying B, Wang M. Multiplex detection of meningitis and encephalitis pathogens: A study from laboratory to clinic. Front Neurol 2022; 13:1054071. [PMID: 36588904 PMCID: PMC9800896 DOI: 10.3389/fneur.2022.1054071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 11/25/2022] [Indexed: 12/23/2022] Open
Abstract
Introduction Infectious meningitis and encephalitis (ME) are life-threatening conditions are caused by various pathogens. Conventional laboratory tests with low sensitivity and specificity cannot help with early diagnosis. Methods A prospective study using the novel multiplex PCR detection for 18 pathogens of ME (MME-18) was conducted to investigate the clinical utilization and the epidemiology characteristics of ME in southwestern China. Patients with suspected intracranial infection were recruited between May and October 2019 at West China Hospital of Sichuan University. The MME-18 was used to detect cerebrospinal fluid, and conventional experiments including cryptococcal capsular antigen detection, GeneXpert, real-time PCR, and clinical feedback were used to verify the result of MME-18. Results Among 581 tested patients, 139 eligible individuals were enrolled in the study. Among them, Mycobacterium tuberculosis was the most common pathogen in mono-infection. Viruses and Cryptococcus neoformans were also frequently detected. Of 139 infected patients, 12 cases were diagnosed by MME-18 only, 57 patients by conventional testing only, and 70 cases by both comparator tests and MME-18. There were 96.3% (79/82) diagnoses made by MME-18 had a favorable outcome, and two of twelve diagnoses, made solely by MME-18, had a likely unclear clinical significance. Discussion The MME-18 showed satisfactory consistency with expert clinical consensus for patients presenting with ME. Combined with conventional testing and clinical suspicion, MME-18 may help clinicians with the early identification of pathogens.
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Affiliation(s)
- Yanjun Si
- Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Weijun He
- Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Shuo Guo
- Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Xiaohui Wang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China,Center for Infectious Diseases, Yaan People's Hospital, Yaan, Sichuan, China
| | - Meng Tang
- Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Binwu Ying
- Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China,Binwu Ying ✉
| | - Minjin Wang
- Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China,*Correspondence: Minjin Wang ✉
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Picard L, Mailles A, Fillâtre P, Tattevin P, Stahl JP. Encephalitis in travellers: A prospective multicentre study. J Travel Med 2022; 30:6869133. [PMID: 36461934 DOI: 10.1093/jtm/taac145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/12/2022] [Accepted: 11/29/2022] [Indexed: 12/07/2022]
Abstract
BACKGROUND As the epidemiology of encephalitis varies from one country to another, international travel may be an important clue for the diagnostic workout of this puzzling disease. METHODS We performed an ancillary study using the ENCEIF prospective cohort conducted in 62 clinical sites in France from 2016 to 2019. All cases of encephalitis in adults that fulfilled a case definition derived from the International Encephalitis Consortium were included. Travellers were defined as patients who spent at least one night in a foreign country within the last six months. RESULTS Of the 494 encephalitis patients enrolled, 69 (14%) were travellers. As compared to non-travellers, they were younger (median age, 48 years [interquartile range, 36-69] vs. 66 [49-76], P < 0.001), less likely to be immunocompromised: 2/69 (3%) vs 56/425 (13%), P = 0.02, and reported more arthralgia: 7/69 (10%) vs. 11/425 (3%), P = 0.007. The risk of poor outcome at hospital discharge (Glasgow outcome scale ≤ 3), was similar for travellers and for non-travellers after adjustment (aOR 0.80 [0.36-1.80], P = 0.594). Arboviruses were the main causes of encephalitis in travellers: 15/69 (22%) vs. 20/425 (5%) in non-travellers, P < 0.001, and Herpes simplex virus (HSV) was the second (9/69, 13%). Of note, in 19% (13/69) of cases, the risk of encephalitis in travellers may have been decreased with a vaccine. CONCLUSION The two primary causes of encephalitis in travellers are arboviruses, and HSV. Empirical treatment of encephalitis in travellers must include aciclovir. Pre-travel advice and vaccination may decrease the risk of encephalitis in travellers.
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Affiliation(s)
- Léa Picard
- Université Rennes 1, Service des Maladies Infectieuses et Réanimation Médicale, Centre Hospitalo-Universitaire, Rennes, France
| | - Alexandra Mailles
- Santé Publique France, Direction des Maladies Infectieuses, Saint-Maurice, France.,European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infectious diseases of the Brain (ESGIB), Basel, Switzerland
| | - Pierre Fillâtre
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infectious diseases of the Brain (ESGIB), Basel, Switzerland.,Service de Réanimation Polyvalente, Centre Hospitalier, Saint-Brieuc, France
| | - Pierre Tattevin
- Université Rennes 1, Service des Maladies Infectieuses et Réanimation Médicale, Centre Hospitalo-Universitaire, Rennes, France.,European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infectious diseases of the Brain (ESGIB), Basel, Switzerland
| | - Jean-Paul Stahl
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infectious diseases of the Brain (ESGIB), Basel, Switzerland.,Université Grenoble Alpes, Maladies Infectieuses, France
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20
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Petitgas P, Tattevin P, Mailles A, Fillâtre P, Stahl JP. Infectious encephalitis in elderly patients: a prospective multicentre observational study in France 2016-2019. Infection 2022:10.1007/s15010-022-01927-3. [PMID: 36152225 DOI: 10.1007/s15010-022-01927-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 09/15/2022] [Indexed: 12/01/2022]
Abstract
PURPOSE Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. METHODS We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years. RESULTS Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥ 65 years, including 74 (15%) ≥ 80 years. Patients ≥ 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm3[13-220] in 65-79 years, 62 [17-180] in ≥ 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥ 80 years (P < 0.001). Age ≥ 80 years, coma on admission, CSF protein ≥ 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality. CONCLUSION Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.
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Affiliation(s)
- Paul Petitgas
- Service des Maladies Infectieuses et Réanimation Médicale, Université Rennes 1, Hôpital Pontchaillou, Centre Hospitalo-Universitaire (CHU), 35000, Rennes, France.,Service des Maladies Infectieuses et de Médecine Interne, CHU de Saint-Pierre, La Réunion, France
| | - Pierre Tattevin
- Service des Maladies Infectieuses et Réanimation Médicale, Université Rennes 1, Hôpital Pontchaillou, Centre Hospitalo-Universitaire (CHU), 35000, Rennes, France.
| | - Alexandra Mailles
- Santé Publique France, Direction des Maladies Infectieuses, Saint-Maurice, France
| | - Pierre Fillâtre
- Service de Réanimation Polyvalente, Saint-Brieuc, CH, France
| | - Jean-Paul Stahl
- Université Grenoble Alpes, CHU, Maladies Infectieuses, Grenoble, France
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21
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Hoogewoud F, Rossi DC, Stappler T, Guex-Crosier Y. Acute retinal necrosis: A mini review. FRONTIERS IN OPHTHALMOLOGY 2022; 2:916113. [PMID: 38983554 PMCID: PMC11182167 DOI: 10.3389/fopht.2022.916113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 08/04/2022] [Indexed: 07/11/2024]
Abstract
Acute retinal necrosis is a rare but potentially devastating disease. Even in the era of modern medicine, retinal detachment is a frequent complication leading to vison loss, as well as phthisis bulbi. Whereas IV acyclovir still remains the standard of care, high doses of valacyclovir with/without additional intravitreal injections of foscarnet have been used. In an attempt to reduce the retinal detachment rate, prophylactic laser treatment and early vitrectomy have been proposed. In this article, we aim to review current diagnostic and treatment modalities.
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22
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Chen YY, Guo Y, Xue XH, Pang F. Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment. World J Clin Cases 2022; 10:7760-7771. [PMID: 36158512 PMCID: PMC9372857 DOI: 10.12998/wjcc.v10.i22.7760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 04/27/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The diagnostic value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infectious diseases after empirical treatment has not been reported.
AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid (CSF) in the empirically treated CNS infectious diseases.
METHODS A total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021. Both mNGS and conventional methods were used for testing. The conventional methods included microbial culture, smear, polymerase chain reaction, etc.
RESULTS Among 262 suspected cases, 183 cases (69.84%) were diagnosed as CNS infection, including 86 cases of virus infection (47.00%), 70 cases of bacterial infection (38.25%) and 27 cases of fungal infection (14.76%). The sensitivity and specificity of mNGS were 65.6% (95%CI: 58.2%-72.3%) and 89.6% (95%CI: 79.1%-95.3%), respectively. The PPV of mNGS was 94.5% (95%CI: 88.6%-97.6%), and the NPV was 48.8% (95%CI: 39.7%–57.9%). The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods (Sensitivity: 65.6% vs 37.2%; P < 0.001; Accuracy: 72.0% vs 50%, P < 0.001). The results showed that compared with conventional methods, mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment.
CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.
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Affiliation(s)
- Ying-Ying Chen
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Yan Guo
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Xin-Hong Xue
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Feng Pang
- Central Laboratory, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
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23
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Vaugon E, Mircescu A, Caya C, Yao M, Gore G, Dendukuri N, Papenburg J. Diagnostic accuracy of rapid one-step PCR assays for detection of herpes Simplex virus -1 and -2 in cerebrospinal fluid: A systematic Review and meta-analysis. Clin Microbiol Infect 2022; 28:1547-1557. [PMID: 35718347 DOI: 10.1016/j.cmi.2022.06.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 04/26/2022] [Accepted: 06/03/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Rapid and accurate diagnosis of HSV-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management. OBJECTIVES Summarize the diagnostic accuracy of commercial rapid sample-to-answer PCR assays (results in <90 minutes, without a separate nucleic acid extraction step) for HSV1/2 detection in CSF. DATA SOURCES Four databases (MEDLINE, EMBASE, Scopus and CENTRAL) and five conference abstract datasets from January 2012 to March 2022. STUDY ELIGIBILITY CRITERIA Diagnostic accuracy studies of FilmArray Meningitis-Encephalitis Panel™ and Simplexa™ HSV 1&2 Direct Kit compared to a PCR reference standard were included. Eligible studies provided sufficient data for the construction of a standard diagnostic accuracy two-by-two table. PARTICIPANTS Patients with suspected meningitis and/or encephalitis. ASSESSMENT OF RISK OF BIAS Two investigators independently extracted data, rated risk of bias and assessed quality using QUADAS-2. METHODS Accuracy estimates were pooled using Bayesian random effects models. RESULTS Thirty-one studies were included (27 FilmArray; 4 Simplexa), comprising 9,924 samples, with 95 HSV-1 and 247 HSV-2 infections. Pooled FilmArray sensitivities were 84.3% (95% credible interval 72.3%-93.0%) and 92.9% (95%CrI, 82.0%-98.5%) for HSV-1 and HSV-2, respectively; specificities were 99.8% (95%CrI, 99.6%-99.9%) and 99.9% (95%CrI, 99.9%-100%). Pooled Simplexa sensitivities were 97.1% (95%CrI, 88.1%-99.6%) and 97.9% (95%CrI, 89.6%-99.9%), respectively; specificities were 98.9% (95%CrI, 96.8%-99.7%) and 98.9% (95%CrI, 97.1%-99.7%). Pooled FilmArray sensitivities favored industry-sponsored studies by 10.0 and 13.0 percentage points for HSV-1 and HSV-2, respectively. Incomplete reporting frequently led to unclear risk of bias. Several FilmArray studies did not fully report true negative data leading to their exclusion. CONCLUSION Our results suggest Simplexa is accurate for HSV1/2 detection in CSF. Moderate FilmArray sensitivity for HSV-1 suggests additional testing and/or repeat CSF sampling is required for suspected HSV encephalitis when the HSV-1 result is negative. Low prevalence of HSV-1 infections limited summary estimates' precision. Underreporting of covariates limited exploration of heterogeneity.
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Affiliation(s)
- Esther Vaugon
- Division of Paediatric Infectious Diseases, Department of Paediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada
| | | | - Chelsea Caya
- Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mandy Yao
- Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal, Quebec, Canada
| | - Genevieve Gore
- Schulich Library of Physical Sciences, Life Sciences, and Engineering, McGill University Montreal, Quebec, Canada
| | - Nandini Dendukuri
- Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
| | - Jesse Papenburg
- Division of Paediatric Infectious Diseases, Department of Paediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada; Division of Microbiology, Department of Clinical Laboratory Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
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24
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Enterovirus meningitis in Mayotte French Comoros Island, March-June 2019. J Clin Virol 2022; 150-151:105154. [DOI: 10.1016/j.jcv.2022.105154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 03/11/2022] [Accepted: 04/02/2022] [Indexed: 11/19/2022]
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Wang Q, Yan S, Zhang J, Du R, Xue L, Li J, Yu C. The differentially expressed proteins related to clinical viral encephalitis revealed by proteomics. IBRAIN 2022; 8:148-164. [PMID: 37786892 PMCID: PMC10528792 DOI: 10.1002/ibra.12036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 04/07/2022] [Accepted: 04/10/2022] [Indexed: 02/05/2023]
Abstract
To screen out the prospective biomarkers of viral encephalitis (VE), analyze the biological process and signaling pathways involved by differentially expressed proteins (DEPs). A total of 11 cerebrospinal fluid (CSF) samples with VE and 5 with non-nervous system infection were used to perform label-free proteomic techniques. Then, the bioinformatic analysis of DEPs was applied by Interproscan software. Moreover, 73 CSF samples in the VE group and 53 in the control group were used to verify the changes of some DEPs by enzyme-linked immunosorbent assay (ELISA). Thirty-nine DEPs were identified, including 18 upregulated DEPs and 21 downregulated DEPs. DEPs were mainly enriched in cell adhesion molecules by Kyoto Encyclopedia of Genes and Genomes analysis pathway analysis. The DEPs related to axon tissue were obviously downregulated and the most significant downregulated proteins were neurexin 3, neurofascin, and neuroligin 2 (NLGN2). Moreover, the protein expression of NLGN2 in the VE group was significantly higher than that in the control group by ELISA. The correlation analysis of NLGN2 in the VE group revealed that there was a weak positive correlation with CSF protein and a weak negative correlation with CSF chloride. The clinical VE may be closely related to NLGN2 and the cell adhesion molecule pathway.
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Affiliation(s)
- Qian Wang
- Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
| | | | | | - Ruo‐Lan Du
- Institute of Neurological Disease and Department of Anesthesiology, Translational Neuroscience Center, West China HospitalSichuan UniversityChengduChina
| | - Lu‐Lu Xue
- Kunming Medical UniversityKunmingYunnanChina
| | - Juan Li
- Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
| | - Chang‐Yin Yu
- Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina
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26
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Guo Y, Yang Y, Xu M, Shi G, Zhou J, Zhang J, Li H. Trends and Developments in the Detection of Pathogens in Central Nervous System Infections: A Bibliometric Study. Front Cell Infect Microbiol 2022; 12:856845. [PMID: 35573778 PMCID: PMC9100591 DOI: 10.3389/fcimb.2022.856845] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 03/29/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction Rapid, sensitive, and specific laboratory assays are critical for the diagnosis and management of central nervous system (CNS) infections. The purpose of this study is to explore the intellectual landscape of research investigating methods for the detection of pathogens in patients with CNS infections and to identify the development trends and research frontier in this field. Methods A bibliometric study is conducted by analyzing literature retrieved from the Web of Science (WoS) Core Collection Database for the years 2000 to 2021. CiteSpace software is used for bibliometric analysis and network visualization, including co-citation analysis of references, co-occurrence analysis of keywords, and cooperation network analysis of authors, institutions, and countries/regions. Results A total of 2,282 publications are eventually screened, with an upward trend in the number of publications per year. The majority of papers are attributed to the disciplines of MICROBIOLOGY, INFECTIOUS DISEASES, IMMUNOLOGY, NEUROSCIENCES & NEUROLOGY, and VIROLOGY. The co-citation analysis of references shows that recent research has focused on the largest cluster “metagenomic next-generation sequencing”; the results of the analysis of the highest-cited publications and the citation burst of publications reveal that there is a strong interest stimulated in metagenomic next-generation sequencing. The co-occurrence analysis of keywords indicates that “infection”, “pathogen”, “diagnosis”, “gene”, “virus”, “polymerase chain reaction”, “cerebrospinal fluid”, “epidemiology”, and “metagenomic next-generation sequencing” are the main research priorities in the field of pathogen detection for CNS infections, and the keyword with the highest strength of burst is “metagenomic next-generation sequencing”. Collaborative network analysis reveals that the USA, the Centers for Disease Control and Prevention of USA, and XIN WANG and JENNIFER DIEN BARD are the most influential country, institution, and researchers, respectively. Conclusions Exploring more advanced laboratory assays to improve the diagnostic accuracy of pathogens is essential for CNS infection research. Metagenomic next-generation sequencing is emerging as a novel useful unbiased approach for diagnosing infectious diseases of the CNS.
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Affiliation(s)
- Yangyang Guo
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yanlin Yang
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ming Xu
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Guangzhi Shi
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jianxin Zhou
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
- *Correspondence: Jindong Zhang, ; Hongliang Li,
| | - Hongliang Li
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- *Correspondence: Jindong Zhang, ; Hongliang Li,
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27
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Mirouse A, Sonneville R, Razazi K, Merceron S, Argaud L, Bigé N, Faguer S, Perez P, Géri G, Guérin C, Moreau AS, Papazian L, Robert R, Barbier F, Ganster F, Mayaux J, Azoulay E, Canet E. Neurologic outcome of VZV encephalitis one year after ICU admission: a multicenter cohort study. Ann Intensive Care 2022; 12:32. [PMID: 35380296 PMCID: PMC8982685 DOI: 10.1186/s13613-022-01002-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 03/18/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Varicella-zoster virus (VZV) is one of the main viruses responsible of acute encephalitis. However, data on the prognosis and neurologic outcome of critically ill patients with VZV encephalitis are limited. We aimed to describe the clinical features of VZV encephalitis in the ICU and to identify factors associated with a favorable neurologic outcome. We performed a multicenter cohort study of patients with VZV encephalitis admitted in 18 ICUs in France between 2000 and 2017. Factors associated with a favorable neurologic outcome, defined by a modified Rankin Score (mRS) of 0-2 1 year after ICU admission, were identified by multivariable regression analysis. RESULTS Fifty-five patients (29 (53%) men, median age 53 (interquartile range 36-66)) were included, of whom 43 (78%) were immunocompromised. ICU admission occurred 1 (0-3) day after the onset of neurological symptoms. Median Glasgow Coma Score at ICU admission was 12 (7-14). Cerebrospinal fluid examination displayed a median leukocyte count of 68 (13-129)/mm3, and a median protein level of 1.37 (0.77-3.67) g/L. CT scan and MRI revealed brain lesions in 30% and 66% of the cases, respectively. Invasive mechanical ventilation was implemented in 46 (84%) patients for a median duration of 13 (3-30) days. Fourteen (25%) patients died in the ICU. One year after ICU admission, 20 (36%) patients had a favorable neurologic outcome (mRS 0-2), 12 (22%) had significant disability (mRS 3-5), and 18 (33%) were deceased (lost to follow-up n = 5, 9%). On multivariable analysis, age (OR 0.92 per year, (0.88-0.97), p = 0.01), and invasive mechanical ventilation (OR 0.09 CI 95% (0.01-0.84), p = 0.03) reduced the likelihood of favorable neurologic outcome. CONCLUSION One in every three critically ill patients with VZV encephalitis had a favorable neurologic outcome 1 year after ICU admission. Older age and invasive mechanical ventilation were associated with a higher risk of disability and death.
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Affiliation(s)
- Adrien Mirouse
- Service de Médecine Intensive et Réanimation, Hôpital Saint-Louis, AP-HP, Paris, France. .,Université de Paris, Paris, France. .,Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, APHP, 83 boulevard de l'hôpital, 75013, Paris, France.
| | - Romain Sonneville
- Université de Paris, Paris, France.,Service de Médecine Intensive et Réanimation, Hôpital Bichat, APHP, Paris, France
| | - Keyvan Razazi
- Service de Médecine Intensive et Réanimation, Hôpital Henri Mondor, Créteil, France
| | - Sybille Merceron
- Service de Réanimation Polyvalente, Hôpital André Mignot, Le Chesnay, France
| | - Laurent Argaud
- Service de Médecine Intensive et Réanimation, Hôpital E. Herriot, Hospices Civils de Lyon, Lyon, France
| | - Naïke Bigé
- Service de Médecine Intensive et Réanimation, Hôpital Saint-Antoine, APHP, Paris, France
| | - Stanislas Faguer
- Département de Néphrologie et Transplantation d'organes - Unité de Réanimation, CHU de Toulouse, Toulouse, France
| | - Pierre Perez
- Service de Réanimation Médicale, Hôpital Brabois, Nancy, France
| | - Guillaume Géri
- Service de Médecine Intensive et Réanimation, Hôpital Cochin, APHP, Paris, France
| | - Claude Guérin
- Service de médecine intensive et réanimation, Groupement Hospitalier Nord, Hospices Civils de Lyon, Université de Lyon, INSERM 955, Créteil, France.,Service de Médecine Intensive et Réanimation Groupement Hospitalier Centre, Hôpital Edouard Herriot, Lyon, France
| | - Anne-Sophie Moreau
- Service de Réanimation Polyvalente, CHRU de Lille - Hôpital Roger Salengro, Lille, France
| | - Laurent Papazian
- Service de Réanimation des Détresses Respiratoires et Infections Sévères, Hôpital Nord, AP-HM, Marseille, France
| | - René Robert
- Service de Réanimation Médicale, CHU de Poitiers, Poitiers, France
| | - François Barbier
- Service de Réanimation Médicale, Hôpital la Source, Orléans, France
| | | | - Julien Mayaux
- Service de Médecine Intensive et Réanimation, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France
| | - Elie Azoulay
- Service de Médecine Intensive et Réanimation, Hôpital Saint-Louis, AP-HP, Paris, France.,Université de Paris, Paris, France
| | - Emmanuel Canet
- Service de Médecine Intensive et Réanimation, CHU de Nantes, Nantes, France
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28
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Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid. Crit Care Med 2022; 50:e643-e648. [PMID: 35167501 DOI: 10.1097/ccm.0000000000005485] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis. DESIGN Retrospective multicenter study from 2007 to 2017. SETTING Forty-seven French ICUs. PATIENTS Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78). CONCLUSIONS In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.
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Lenfant T, L'Honneur A, Ranque B, Pilmis B, Charlier C, Zuber M, Pouchot J, Rozenberg F, Michon A. Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid. Brain Behav 2022; 12:e2455. [PMID: 35040287 PMCID: PMC8865153 DOI: 10.1002/brb3.2455] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 11/05/2021] [Accepted: 11/11/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND VZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown. METHODS This is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta. RESULTS Seventy-two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty-two patients completed follow-up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd-ratio (OR) 3.1 [1.4-8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4-181] p = .001, OR 6.2 [1.3-33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta. CONCLUSIONS Neurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively.
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Affiliation(s)
- Tiphaine Lenfant
- Université de Paris, Service de Médecine InterneHôpital Européen Georges Pompidou, AP‐HPParisFrance
| | | | - Brigitte Ranque
- Université de Paris, Service de Médecine InterneHôpital Européen Georges Pompidou, AP‐HPParisFrance
| | - Benoit Pilmis
- Équipe Mobile de Microbiologie CliniqueGroupe Hospitalier Paris Saint JosephParisFrance
| | - Caroline Charlier
- Université de Paris, Equipe Mobile InfectiologieHôpital Cochin Port‐Royal, AP‐HPUnité Biologie des Infections, Institut Pasteur, Inserm U1117ParisFrance
| | - Mathieu Zuber
- Service de Neurologie et NeurovasculaireGroupe Hospitalier Paris Saint JosephParisFrance
| | - Jacques Pouchot
- Université de Paris, Service de Médecine InterneHôpital Européen Georges Pompidou, AP‐HPParisFrance
| | - Flore Rozenberg
- Université de Paris, Service de VirologieHôpital Cochin, AP‐HPParisFrance
| | - Adrien Michon
- Université de Paris, Service de Médecine InterneHôpital Européen Georges Pompidou, AP‐HPParisFrance
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Mulatero M, Boucekine M, Felician O, Boussen S, Kaplanski G, Rossi P, Parola P, Stein A, Brouqui P, Lagier JC, Leone M, Kaphan E. Herpetic encephalitis: which treatment for which body weight? J Neurol 2022; 269:3625-3635. [DOI: 10.1007/s00415-022-10981-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 01/01/2022] [Accepted: 01/19/2022] [Indexed: 10/19/2022]
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Zhang Y, Zhang H, Deng B, Lin K, Jin L, Liu X, Zhang Y, Chen X, Zhang Y, Lu S, Huang H, Wang Q, Feng T, Zhao W, Xue Q, Chen R, Zhang J, Qian X, Chen L, Ai J, Chen X, Zhang W. Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial. BMC Infect Dis 2022; 22:40. [PMID: 34998377 PMCID: PMC8742395 DOI: 10.1186/s12879-021-06943-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/03/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. METHODS IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. DISCUSSION To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.
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Affiliation(s)
- Yi Zhang
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Haocheng Zhang
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Bo Deng
- Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ke Lin
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Lei Jin
- Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaoni Liu
- Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yanlin Zhang
- Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Xiaohua Chen
- Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, China
| | - Yanliang Zhang
- Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Shengjia Lu
- Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, China
| | - Heqing Huang
- Department of Infectious Diseases, Zhuji People's Hospital of Zhejiang Province, Shaoxing, Zhejiang Province, China
| | - Qiujing Wang
- Department of Infectious Diseases, Zhoushan Hospital of Zhejiang Province, Zhoushan, Zhejiang Province, China
| | - Tingting Feng
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Weifeng Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Qun Xue
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Renfang Chen
- Department of Infectious Diseases, Wuxi No.5 People 's Hospital, Wuxi, Jiangsu Province, China
| | - Jingbo Zhang
- Department of Neurology, Blue Cross Brain Hospital, Shanghai, China
| | - Xiaoyan Qian
- Department of Neurology, The first people's hospital of Kunshan, Suzhou, Jiangsu Province, China
| | - Lanlan Chen
- Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu Province, China
| | - Jingwen Ai
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China.
| | - Xiangjun Chen
- Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
| | - Wenhong Zhang
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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Gaudin M, Theïs C, Mrozek N, Brebion A, Henquell C, Jacomet C, Vidal M. Varicella zoster virus and meningitis in immunocompetent patients: Specificity and questions. CLINICAL INFECTION IN PRACTICE 2022. [DOI: 10.1016/j.clinpr.2021.100125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Sonneville R, Jaquet P, Vellieux G, de Montmollin E, Visseaux B. Intensive care management of patients with viral encephalitis. Rev Neurol (Paris) 2021; 178:48-56. [PMID: 34973832 DOI: 10.1016/j.neurol.2021.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/13/2021] [Indexed: 11/26/2022]
Abstract
Viral encephalitis is a severe syndrome that can lead to encephalopathy, seizures, focal deficits, and neurological sequelae and death. It is mainly caused by neurotropic herpes viruses (i.e., HSV and VZV), although other pathogens may be observed in specific geographic regions or conditions. Recent advances in neuroimaging and molecular biology (PCR, metagenomics) allow for faster and more accurate etiological diagnoses, although their benefits need to be confirmed to provide guidelines for their use and interpretation. Despite intravenous acyclovir therapy and supportive care, outcomes remain poor in about two-thirds of herpes encephalitis patients requiring ICU admission. Randomized clinical trials focusing on symptomatic measures (i.e. early ICU admission, fever control, and treatment of seizures/status epilepticus) or adjunctive immunomodulatory therapies (i.e. steroids, intravenous immunoglobulins) to improve neurologic outcomes have not been conducted in the ICU setting. Large prospective multicenter studies combining clinical, electrophysiological, and neuroimaging data are needed to improve current knowledge on care pathways, long-term outcomes, and prognostication.
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Affiliation(s)
- R Sonneville
- Université de Paris, INSERM UMR1148, team 6, 75018 Paris, France; AP-HP, intensive care medicine, Hôpital Bichat - Claude Bernard, 75018 Paris, France.
| | - P Jaquet
- AP-HP, intensive care medicine, Hôpital Bichat - Claude Bernard, 75018 Paris, France
| | - G Vellieux
- AP-HP, department of Physiology, Hôpital Bichat - Claude Bernard, 75018 Paris, France
| | - E de Montmollin
- Université de Paris, INSERM UMR1148, team 6, 75018 Paris, France; Université de Paris, INSERM UMR1137, team 6, 75018 Paris, France
| | - B Visseaux
- Université de Paris, INSERM UMR1137, team 6, 75018 Paris, France; AP-HP, department of virology, Hôpital Bichat - Claude Bernard, 75018 Paris, France
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Mailles A, Argemi X, Biron C, Fillatre P, De Broucker T, Buzelé R, Gagneux-Brunon A, Gueit I, Henry C, Patrat-Delon S, Makinson A, Piet E, Wille H, Vareil MO, Epaulard O, Martinot M, Tattevin P, Stahl JP. Changing profile of encephalitis: Results of a 4-year study in France. Infect Dis Now 2021; 52:1-6. [PMID: 34896660 DOI: 10.1016/j.idnow.2021.11.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 11/01/2021] [Accepted: 11/26/2021] [Indexed: 11/16/2022]
Abstract
CONTEXT In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson's Chi2 test, and means were compared using Student's t-test for continuous variables. RESULTS We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines.
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Affiliation(s)
- A Mailles
- Santé Publique France, Saint-Maurice, France; ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland.
| | - X Argemi
- Infectious diseases and internal medicine department, Axium clinic, Aix-en-Provence, France
| | - C Biron
- Infectious diseases department, CHU Hôtel-Dieu, INSERM UIC 1413, Nantes university, Nantes, France
| | - P Fillatre
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland; Intensive care unit, hôpital Yves-le-Foll, Saint-Brieuc, France
| | | | - R Buzelé
- Infectious diseases unit, hôpital Yves-le-Foll, Saint-Brieuc, France
| | - A Gagneux-Brunon
- Infectious diseases department, hôpital Nord, CHU Saint-Étienne, Saint-Priest-en-Jarez, France
| | - I Gueit
- Department of infectious diseases, CHU Rouen, Rouen, France
| | - C Henry
- Neurology, CH Delafontaine, Saint-Denis, France
| | - S Patrat-Delon
- Infectious diseases department, CHU Ponchaillou, Rennes, France
| | - A Makinson
- Infectious diseases and intensive care unit, Pontchaillou university hospital, Rennes, France
| | - E Piet
- Infectious diseases department, CH Annecy-Genevois, Metz Tessy, France
| | - H Wille
- Infectious diseases department, CH Côte Basque, 64109 Bayonne, France
| | - M O Vareil
- Infectious diseases department, CH Côte Basque, 64109 Bayonne, France
| | - O Epaulard
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland; Université Grenoble Alpes, CHUGA, infectious diseases department, Grenoble, France
| | - M Martinot
- Infectious diseases department CH Colmar, Colmar, France
| | - P Tattevin
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland; Infectious diseases department, CHU Ponchaillou, Rennes, France
| | - J P Stahl
- ESCMID Study Group on the infections of the Brain (ESGIB), Basel, Switzerland; Université Grenoble Alpes, CHUGA, infectious diseases department, Grenoble, France
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Stalteri Mastrangelo R, Santesso N, Bognanni A, Darzi A, Karam S, Piggott T, Baldeh T, Schünemann F, Ventresca M, Morgano GP, Moja L, Loeb M, Schunemann H. Consideration of antimicrobial resistance and contextual factors in infectious disease guidelines: a systematic survey. BMJ Open 2021; 11:e046097. [PMID: 34330853 PMCID: PMC8327810 DOI: 10.1136/bmjopen-2020-046097] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 06/14/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Guidelines that include antimicrobial recommendations should explicitly consider contextual factors that influence antimicrobial resistance and their downstream effects on resistance selection. The objectives were to analyse (1) how, and to what extent, tuberculosis, gonorrhoea and respiratory tract infection guidelines are considering antimicrobial resistance; (2) are of acceptable quality and (3) if they can be easily contextualised to fit the needs of specific populations and health systems. METHODS We conducted a systematic review and searched Ovid MEDLINE and Embase from 1 January 2007 to 7 June 2019 for tuberculosis, gonorrhoea and respiratory tract infection guidelines published in English. We also searched guideline databases, key websites and reference lists. We identified guidelines and recommendations that considered contextual factors including antimicrobial resistance, values, resource use, equity, acceptability and feasibility. We assessed quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool focusing on the domains scope and purpose, rigour of development, and editorial independence. RESULTS We screened 10 365 records, of which 74 guidelines met inclusion criteria. Of these guidelines, 39% (n=29/74) met acceptable quality scores. Approximately two-thirds of recommendations considered antimicrobial resistance at the population and/or outcome level. Five of the 29 guidelines reported all factors required for recommendation contextualisation. Equity was the least considered across guidelines. DISCUSSION Relatively few guidelines for highly prevalent infectious diseases are considering resistance at a local level, and many do not consider contextual factors necessary for appropriate antimicrobial use. Improving the quality of guidelines targeting specific regional areas is required. PROSPERO REGISTRATION NUMBER CRD42020145235.
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Affiliation(s)
- Rosa Stalteri Mastrangelo
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Nancy Santesso
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
| | - Antonio Bognanni
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Andrea Darzi
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
| | - Samer Karam
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
| | - Thomas Piggott
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
| | - Tejan Baldeh
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
| | - Finn Schünemann
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
- Institut für Evidence in Medicine, Medical Center & Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Matthew Ventresca
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Gian Paolo Morgano
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Lorenzo Moja
- Department of Health Product Policy and Standards, World Health Organization, Geneva, Switzerland
| | - Mark Loeb
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Holger Schunemann
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Michael G. DeGroote Cochrane Canada and MacGRADE Centres, McMaster University, Hamilton, Ontario, Canada
- Institut für Evidence in Medicine, Medical Center & Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Hansen MA, Hasbun R. US Hospitalizations and 60-Day Readmission Rates Associated with Herpes simplex virus Encephalitis: Analysis of All Cause Readmissions and Encephalopathy Associated Readmissions. Clin Infect Dis 2021; 74:1174-1182. [PMID: 34240104 DOI: 10.1093/cid/ciab613] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Herpes simplex encephalitis (HSE) is the most common cause of encephalitis hospitalizations. We sought to describe and analyze features associated with all cause readmissions and encephalopathy associated readmissions amongst HSE cases. METHODS HSE hospitalizations and 60-day rehospitalizations were assessed in a retrospective cohort using linked hospitalizations from the Healthcare Utilization Project (HCUP) National Readmission Database (NRD) from 2010 through 2017. Risk factors for all-cause readmissions and encephalopathy associated readmissions were assessed with a weighted logistic regression model. RESULTS There were 10,272 HSE cases in the US between 2010 and 2017, resulting in a national rate of 4.95 per 100,000 hospitalizations. A total of 23.7% were readmitted at least once within 60-days. Patients that were readmitted were older (mean age 62.4 vs. 57.9, p<0.001), had a greater number of procedures at the index hospitalization (aOR 1.03, p<0.001) and have a higher Charlson comorbidity score (aOR 1.11, p<0.001). Amongst those readmitted, 465 (16.5%) had an encephalopathy related diagnosis. Over eight years, the rate of encephalopathy associated readmissions increased from 0.12 to 0.20. Encephalopathy specific readmissions were found to be associated with greater age (mean age 65.9 vs. 61.7, p = 0.004) and findings of cerebral edema at index hospitalization (aOR 2.16, p <0.001). CONCLUSIONS HSE readmissions are relatively common, particularly among older and sicker individuals. However, early signs and symptoms of neurological disease at index were correlated with encephalopathic specific readmissions.
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Affiliation(s)
- Michael A Hansen
- Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX
| | - Rodrigo Hasbun
- Division of Infectious Disease, Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX
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Sarton B, Jaquet P, Belkacemi D, de Montmollin E, Bonneville F, Sazio C, Frérou A, Conrad M, Daubin D, Chabanne R, Argaud L, Dailler F, Brulé N, Lerolle N, Maestraggi Q, Marechal J, Bailly P, Razazi K, Mateos F, Guidet B, Levrat A, Susset V, Lautrette A, Mira JP, El Kalioubie A, Robert A, Massri A, Albucher JF, Olivot JM, Conil JM, Boudma L, Timsit JF, Sonneville R, Silva S. Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis. JAMA Netw Open 2021; 4:e2114328. [PMID: 34313743 PMCID: PMC8317014 DOI: 10.1001/jamanetworkopen.2021.14328] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 03/15/2021] [Indexed: 01/09/2023] Open
Abstract
Importance Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. Objective To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. Design, Setting, and Participants This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. Exposures All patients underwent a standard brain MRI during the first 30 days after ICU admission. Main Outcomes and Measures MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Results Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). Conclusions and Relevance These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.
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Affiliation(s)
- Benjamine Sarton
- Critical Care Unit, University Hospital of Purpan, Toulouse, France
- Toulouse NeuroImaging Center, Unité Mixte de Recherche 1214, Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France
| | - Pierre Jaquet
- Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, Paris, France
| | - Djida Belkacemi
- Department of Neuroradiology, University Hospital of Purpan, Toulouse, France
| | - Etienne de Montmollin
- Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, Paris, France
| | - Fabrice Bonneville
- Toulouse NeuroImaging Center, Unité Mixte de Recherche 1214, Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France
- Department of Neuroradiology, University Hospital of Purpan, Toulouse, France
| | - Charline Sazio
- Critical Care Unit, University Hospital of Pellegrin, Bordeaux, France
| | - Aurelien Frérou
- Critical Care Unit, University Hospital of Rennes, Rennes, France
| | - Marie Conrad
- Critical Care Unit, Regional and University Hospital of Nancy, Nancy France
| | - Delphine Daubin
- Critical Care Unit, University Hospital of Montpellier, Montpellier, France
| | - Russell Chabanne
- Critical Care Unit, University Hospital Gabriel Montpied, Clermont Ferrand, France
| | - Laurent Argaud
- Critical Care Unit, University Hospital Edouard Herriot, Hospices Civils of Lyon, Lyon, France
| | - Frédéric Dailler
- Neurological Critical Care Unit, Hospital Pierre Wertheimer, Hospices Civils of Lyon, Lyon, France
| | - Noëlle Brulé
- Critical Care Unit, University Hospital of Nantes, Nantes, France
| | - Nicolas Lerolle
- Critical Care Unit, University Hospital of Angers, Angers, France
| | - Quentin Maestraggi
- Critical Care Unit, University Hospital Hautepierre of Strasbourg, Strasbourg, France
| | - Julien Marechal
- Critical Care Unit, University Hospital La Miletrie, Poitiers, France
| | - Pierre Bailly
- Critical Care Unit, Regional University Hospital La Cavale Blanche, Brest, France
| | - Keyvan Razazi
- Critical Care Unit, University Hospital of Henri Mondor, Créteil, France
| | - Francois Mateos
- Critical Care Unit, Regional Hospital of Saint Brieuc, Saint Brieuc, France
| | - Bertrand Guidet
- Critical Care Unit, University Hospital of Saint Antoine, Paris, France
| | - Albrice Levrat
- Critical Care Unit, University Hospital of Annecy Genevois, Epagny Metz-Tessy, France
| | - Vincent Susset
- Critical Care Unit, Regional Hospital of Chambery, Chambery, France
| | - Alexandre Lautrette
- Critical Care Unit, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
| | - Jean-Paul Mira
- Critical Care Unit, University Hospital Cochin, Paris, France
| | | | | | | | - Jean François Albucher
- Toulouse NeuroImaging Center, Unité Mixte de Recherche 1214, Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France
- Department of Neurology, University Hospital of Purpan, Toulouse, France
| | - Jean Marc Olivot
- Toulouse NeuroImaging Center, Unité Mixte de Recherche 1214, Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France
- Department of Neurology, University Hospital of Purpan, Toulouse, France
| | - Jean Marie Conil
- Critical Care Unit, University Hospital of Rangueil, Toulouse, France
| | - Lila Boudma
- Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, Paris, France
| | - Jean-François Timsit
- Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, Paris, France
| | - Romain Sonneville
- Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, Paris, France
- Laboratory for Vascular Translational Science, Sorbonne Paris Cité, Unité Mixte de Recherche 1148, Institut National de la Santé et de la Recherche Médicale, Paris Diderot University, Paris, France
| | - Stein Silva
- Critical Care Unit, University Hospital of Purpan, Toulouse, France
- Toulouse NeuroImaging Center, Unité Mixte de Recherche 1214, Institut National de la Santé et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France
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Bremer M, Kadernani YE, Wasserman S, Wilkinson RJ, Davis AG. Strategies for the diagnosis and management of meningitis in HIV-infected adults in resource limited settings. Expert Opin Pharmacother 2021; 22:2053-2070. [PMID: 34154509 DOI: 10.1080/14656566.2021.1940954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION The incidence of human immunodeficiency virus-1 (HIV-1) associated meningitis has been declining in the post-combination antiretroviral treatment (ART) era, although survival rates remain low for the common causes like tuberculosis and cryptococcal disease. Diagnosis and treatment of meningitis in HIV-1 is complicated by atypical clinical presentations, limited accuracy of diagnostic tests, access to diagnostic tests, and therapeutic agents in low- and middle-income countries (LMIC) and immune reconstitution inflammatory syndrome (IRIS). AREAS COVERED We provide an overview of the common etiologies of meningitis in HIV-1-infected adults, suggest a diagnostic approach based on readily available tests, and review specific chemotherapeutic agents, host-directed therapies, supportive care, timing of ART initiation, and considerations in the management of IRIS with a focus on resource-limited settings. They identify key knowledge gaps and suggest areas for future research. EXPERT OPINION Evidence-based management of HIV-1-associated meningitis is sparse for common etiologies. More readily available and sensitive diagnostic tests as well as standardized investigation strategies are required in LMIC. There is a lack of availability of recommended drugs in areas of high HIV-1 prevalence and a limited pipeline of novel chemotherapeutic agents. Host-directed therapies have been inadequately studied.
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Affiliation(s)
- Marise Bremer
- Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory
| | - Yakub E Kadernani
- Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory
| | - Sean Wasserman
- Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory.,Department of Medicine, University of Cape Town, Groote Schuur Hospital, Observatory, Republic of South Africa
| | - Robert J Wilkinson
- Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory.,Department of Medicine, University of Cape Town, Groote Schuur Hospital, Observatory, Republic of South Africa.,Department of Infectious Diseases, Imperial College London, London, UK.,Francis Crick Institute, London, UK.,Faculty of Life Sciences, University College London, London, UK
| | - Angharad G Davis
- Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory.,Francis Crick Institute, London, UK.,Faculty of Life Sciences, University College London, London, UK
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Ge M, Gan M, Yan K, Xiao F, Yang L, Wu B, Xiao M, Ba Y, Zhang R, Wang J, Cheng G, Wang L, Cao Y, Zhou W, Hu L. Combining Metagenomic Sequencing With Whole Exome Sequencing to Optimize Clinical Strategies in Neonates With a Suspected Central Nervous System Infection. Front Cell Infect Microbiol 2021; 11:671109. [PMID: 34222042 PMCID: PMC8253254 DOI: 10.3389/fcimb.2021.671109] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/27/2021] [Indexed: 12/02/2022] Open
Abstract
Objectives Central nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES). Methods We prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples. Results Eighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect. Conclusions For patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.
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Affiliation(s)
- Mengmeng Ge
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Mingyu Gan
- Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
| | - Kai Yan
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Feifan Xiao
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Lin Yang
- Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
| | - Bingbing Wu
- Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, The Translational Medicine Center of Children Development and Disease of Fudan University, Shanghai, China
| | - Mili Xiao
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Yin Ba
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Rong Zhang
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Jin Wang
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Guoqiang Cheng
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Laishuan Wang
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Yun Cao
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
| | - Wenhao Zhou
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China.,Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
| | - Liyuan Hu
- Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China
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Mathon B, Pineton de Chambrun M, Bielle F, Amelot A, Le Joncour A. Encephalitis of Unknown Etiology? Not Until the Results of a Brain Biopsy! Clin Infect Dis 2021; 72:e432. [PMID: 32756947 DOI: 10.1093/cid/ciaa1093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Bertrand Mathon
- Department of Neurosurgery, Assistance Publique - Hôpitaux de Paris, La Pitié-Salpêtrière, Charles Foix University Hospital, Paris, France.,Sorbonne University, Université Pierre et Marie Curie University Paris, Paris, France.,Brain and Spine Institute (Institut du Cerveau et de la Moelle Epinière; INSERM, UMRS 1127; Centre national de la recherche scientifique, Unité Mixte de Recherche 7225), Paris, France
| | - Marc Pineton de Chambrun
- Sorbonne University, Université Pierre et Marie Curie University Paris, Paris, France.,Department of Internal Medicine 2, AP-HP, La Pitié-Salpêtrière, Charles Foix University Hospital, Paris, France.,Department of Intensive Care Medicine, AP-HP, La Pitié-Salpêtrière, Charles Foix University Hospital, Paris, France.,Sorbonne Université, Institut National de la santé et de la recherche médicale, UMRS_1166-Institute of Cardiometabolism and Nutrition, Institute of Cardiometabolism and Nutrition, Paris, France
| | - Franck Bielle
- Sorbonne University, Université Pierre et Marie Curie University Paris, Paris, France.,Brain and Spine Institute (Institut du Cerveau et de la Moelle Epinière; INSERM, UMRS 1127; Centre national de la recherche scientifique, Unité Mixte de Recherche 7225), Paris, France.,Department of Neuropathology, AP-HP, La Pitié-Salpêtrière, Charles Foix University Hospital, Paris, France
| | - Aymeric Amelot
- Department of Neurosurgery, Assistance Publique - Hôpitaux de Paris, La Pitié-Salpêtrière, Charles Foix University Hospital, Paris, France
| | - Alexandre Le Joncour
- Department of Internal Medicine and Clinical Immunology, AP-HP, La Pitié-Salpêtrière, Charles Foix University Hospital, Paris, France
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Characteristics and outcome of varicella-zoster virus central nervous system infections in adults. Eur J Clin Microbiol Infect Dis 2021; 40:2437-2442. [PMID: 33907935 DOI: 10.1007/s10096-021-04245-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 04/02/2021] [Indexed: 10/21/2022]
Abstract
We conducted an observational retrospective study of all adults hospitalized for documented varicella-zoster virus (VZV) meningitis or encephalitis during years 2000-2015 in one referral centre. Thirty-six patients (21 males, 15 females) were included, with meningitis (n = 21), or meningoencephalitis (n = 15). Median age was 51 years [interquartile range, 35-76], and 6 patients (17%) were immunocompromised. Aciclovir was started in 32 patients (89%), with a median dose of 11 mg/kg/8 h [10-15]. No patient died, but 12 (33%) had neurological sequelae at discharge. Age was the only variable associated with adverse outcome (OR 1.98 [1.17-3.35] per 10-year increment, P = 0.011).
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Invasive neuromonitoring and neurological intensive care unit management in life-threatening central nervous system infections. Curr Opin Neurol 2021; 34:447-455. [PMID: 33935217 DOI: 10.1097/wco.0000000000000945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Patients with infectious diseases of the central nervous system (CNS) commonly require treatment in the intensive care unit (ICU). In a subset of patients with a life-threatening course, a more aggressive and invasive management is required. Treatment relies on the expertise of the intensivists as most recommendations are currently not based on a high level of evidence. RECENT FINDINGS Published data suggest that an invasive brain-focused management should be considered in life-threatening CNS infections. Brain resuscitation by adequate control of intracranial pressure (ICP) and optimization of cerebral perfusion, oxygen and glucose delivery supports the idea of personalized medicine. Recent advances in monitoring techniques help to guide clinicians to improve neurocritical care management in these patients with severe disease. Robust data on the long-term effect of decompressive craniectomy and targeted temperature management are lacking, however, these interventions can be life-saving in individual patients in the setting of a potentially fatal situation such as refractory elevated ICP. SUMMARY Advances in the neurocritical care management and progress in monitoring techniques in specialized neuro-ICUs may help to preserve brain function and prevent a deleterious cascade of secondary brain damage in life-threatening CNS infections.
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Gauzit R, Castan B, Bonnet E, Bru JP, Cohen R, Diamantis S, Faye A, Hitoto H, Issa N, Lebeaux D, Lesprit P, Maulin L, Poitrenaud D, Raymond J, Strady C, Varon E, Verdon R, Vuotto F, Welker Y, Stahl JP. Anti-infectious treatment duration: The SPILF and GPIP French guidelines and recommendations. Infect Dis Now 2021; 51:114-139. [PMID: 34158156 DOI: 10.1016/j.idnow.2020.12.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 12/28/2020] [Indexed: 02/07/2023]
Affiliation(s)
- R Gauzit
- Infectiologie transversale, CHU Cochin, AP-HP, 75014 Paris, France.
| | - B Castan
- Maladies infectieuses et tropicales, CHG, 24000 Périgueux, France
| | - E Bonnet
- Équipe Mobile d'Infectiologie, Hôpital Joseph-Ducuing, Clinique Pasteur, 31300 Toulouse, France
| | - J P Bru
- Maladies Infectieuses, CH Annecy-Genevois, 74374 Pringy, France
| | - R Cohen
- Unité petits nourrissons, CHI, 94000 Créteil, France
| | - S Diamantis
- Maladies Infectieuses et Tropicales, groupe hospitalier Sud Île-de-France, 77000 Melun, France
| | - A Faye
- Pédiatrie Générale et maladies infectieuses, Hôpital Robert-Debré, Université de Paris, AP-HP, 75019 Paris, France
| | - H Hitoto
- Maladies Infectieuses et Tropicales, CH, 72037 Le Mans, France
| | - N Issa
- Réanimation médicale et maladies infectieuses, Hôpital Saint-André, CHU, 33000 Bordeaux, France
| | - D Lebeaux
- Université de Paris, 75006 Paris, France; Microbiologie, Unité Mobile d'Infectiologie, HEGP, AP-HP, 75015 Paris, France
| | - P Lesprit
- Unité transversale d'hygiène et d'infectiologie, Service de Biologie Clinique, Hôpital Foch, 92150 Suresnes, France
| | - L Maulin
- Maladies Infectieuses et tropicales, CHIAP, 13616 Aix-en-Provence, France
| | - D Poitrenaud
- Unité fonctionnelle d'Infectiologie Régionale, CH Ajaccio, 20303 Ajaccio, France
| | - J Raymond
- Bactériologie, Centre Hospitalier Bicêtre, 94270 Kremlin-Bicêtre, France
| | - C Strady
- Cabinet d'infectiologie, Groupe Courlancy, 51100 Reims, France
| | - E Varon
- Laboratoire de Biologie Médicale et Centre National de Référence des Pneumocoques, CHIC, 94000 Créteil, France
| | - R Verdon
- Maladies Infectieuses et Tropicales, CHU, 14033 Caen, France; Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Univ, UNICAEN, UNIROUEN, GRAM 2.0, 14000 Caen, France
| | - F Vuotto
- Maladies Infectieuses, CHU, Hôpital Huriez, 59000 Lille, France
| | - Y Welker
- Maladies Infectieuses, CHI, 78100 Saint-Germain-en-Laye, France
| | - J P Stahl
- Infectiologie, CHU Grenoble Alpes, 38043 Grenoble, France
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Lampros A, Caumes E, Psimaras D, Galanaud D, Clarençon F, Peyre M, Deltour S, Bielle F, Lhote R, Haroche J, Amoura Z, Cohen Aubart F. [Infection associated cerebral vasculitis]. Rev Med Interne 2020; 42:258-268. [PMID: 32868117 DOI: 10.1016/j.revmed.2020.05.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 04/26/2020] [Accepted: 05/07/2020] [Indexed: 12/11/2022]
Abstract
Infections are a frequent cause of cerebral vasculitis, important to diagnose because a specific treatment may be required. Infection-associated vasculitis can be caused by angiotropic pathogens (varicella zoster virus, syphilis, aspergillus). They can be associated with subarachnoidal meningitis (tuberculosis, pyogenic meningitis, cysticercosis). They can appear contiguously to sinuses or orbital infection (aspergillosis, mucormycosis). Finally, they also may be due to an immune mechanism in the context of chronic infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Cerebral vasculitis are severe conditions and their prognosis is directly linked to early recognition and diagnosis. Infectious causes must therefore be systematically considered ahead of cerebral vasculitis, and the appropriate investigations must be determined according to the patient's clinical context. We propose here an update on the infectious causes of cerebral vasculitis, their diagnosis modalities, and therapeutic options.
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Affiliation(s)
- A Lampros
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence Maladies systémiques rares et Histiocytoses, 75013 Paris, France
| | - E Caumes
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service des maladies infectieuses et tropicales, 75013 Paris, France
| | - D Psimaras
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neurologie 2, 75013 Paris, France
| | - D Galanaud
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neuroradiologie, 75013 Paris, France
| | - F Clarençon
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neuroradiologie, 75013 Paris, France
| | - M Peyre
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neurochirurgie, 75013 Paris, France
| | - S Deltour
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service des Urgences cérébro-vasculaires, 75013 Paris, France
| | - F Bielle
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Neuropathologie, 75013 Paris, France
| | - R Lhote
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence Maladies systémiques rares et Histiocytoses, 75013 Paris, France
| | - J Haroche
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence Maladies systémiques rares et Histiocytoses, 75013 Paris, France
| | - Z Amoura
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence Maladies systémiques rares et Histiocytoses, 75013 Paris, France
| | - F Cohen Aubart
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence Maladies systémiques rares et Histiocytoses, 75013 Paris, France.
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Collet A, Baes D, Mambie A, Hembert K, Boulle C, Gana I, Lemaire X. VZV meningoencephalitis treated with ganciclovir. Med Mal Infect 2020; 50:444-445. [DOI: 10.1016/j.medmal.2020.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 09/09/2019] [Accepted: 03/02/2020] [Indexed: 11/26/2022]
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Pisché G, Spitz I, Siffray-Bauer L, Dentel C, Perriard J, Carré S. All that glitters is not gold: A limbic encephalitis due to neurosyphilis. Rev Neurol (Paris) 2020; 177:156-157. [PMID: 32631679 DOI: 10.1016/j.neurol.2020.04.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 04/08/2020] [Accepted: 04/15/2020] [Indexed: 10/23/2022]
Affiliation(s)
- G Pisché
- Service de neurologie, Centre Hospitalier de Haguenau, 64, avenue du Professeur René Leriche, 67500 Haguenau, France.
| | - I Spitz
- Service de neurologie, Centre Hospitalier de Haguenau, 64, avenue du Professeur René Leriche, 67500 Haguenau, France
| | - L Siffray-Bauer
- Service de neurologie, Centre Hospitalier de Haguenau, 64, avenue du Professeur René Leriche, 67500 Haguenau, France
| | - C Dentel
- Service de neurologie, Centre Hospitalier de Haguenau, 64, avenue du Professeur René Leriche, 67500 Haguenau, France
| | - J Perriard
- Service de neurologie, Centre Hospitalier de Haguenau, 64, avenue du Professeur René Leriche, 67500 Haguenau, France
| | - S Carré
- Service de neurologie, Centre Hospitalier de Haguenau, 64, avenue du Professeur René Leriche, 67500 Haguenau, France
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Abstract
PURPOSE OF REVIEW HSV is the most frequently identified cause of infectious encephalitis, in Western countries. This article is an update on the topic based on a review of recent studies from 2017 to 2018. RECENT FINDINGS Acyclovir is still the first line treatment, and no new drugs are currently available for clinical use. The major considerations for HSV encephalitis are as follows: point one, clinical evaluation remains the most important factor, as though CSF HSV PCR has a good sensitivity, in a small proportion of patients the initial testing might be negative. MRI brain is the first line imaging test, and mesial temporal lobe involvement and other typical findings are important for diagnosis; point 2, there should be emphasis on sequela, short-term, and long-term outcomes, and not just case fatality rated in future studies and clinical management. Auto-immune encephalitis can be triggered by HSV, and should be considered in patients who are not responding to treatment; point 3, future studies should be on better management of sequela, and better treatment regimens including those targeting the immune response. SUMMARY Autoimmune encephalitis is a clearly identified complication of HSV encephalitis. Inflammatory mechanisms are linked to the clinical presentation as well as severity and poor outcome. Initial corticosteroid therapy has to be evaluated in order to prevent complications.
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Antiepileptic drugs for acute encephalitic patients presented with seizure. Epilepsy Res 2020; 164:106347. [PMID: 32442843 DOI: 10.1016/j.eplepsyres.2020.106347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/08/2020] [Accepted: 04/22/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The aim of this study was to clarify the pattern and efficacy of antiepileptic drugs (AEDs) in acute encephalitis and discuss how long AEDs should be used after the acute phase. METHODS Patients with acute encephalitis who presented with seizure were enrolled. The clinical features were systematically gathered, and the information about AEDs and seizures was obtained by a clinical follow-up and (or) a telephone interview based on a structured form. RESULTS A total of 327 patients were enrolled, and the mean follow-up period was 63.8 (14-123) months. The risk of seizure relapse was estimated as 43.6% five years after the acute phase and the first three months was the peak time for relapse. Univariate analysis showed that status epilepticus, more than one seizure, cerebral spinal fluid protein level, abnormal MRI finding, temporal lobe involvement, and epileptiform discharge were related to seizure relapse. But only more than one seizure (OR = 2.80 (95% CI 1.29-6.09), p = 0.009) and temporal lobe involvement (5.34 (2.68-10.64), p < 0.001) remain predictive on multivariate regression analysis. For patients with only one seizure and no temporal lobe involvement, the risk of seizure relapse was similar between those with or without AED (2/29 vs. 4/28, p = 0.423). For the rest, the risks of relapse were similar among those who took sodium valproate and levetiracetam. SIGNIFICANCE For patients with only one seizure and no temporal lobe involvement, AEDs may not be strictly needed. The first three months after acute phase was the peak time for relapse and AEDs may should be used during this period. Both sodium valproate and levetiracetam could be selected.
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Zhang Y, Cui P, Zhang HC, Wu HL, Ye MZ, Zhu YM, Ai JW, Zhang WH. Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection. J Transl Med 2020; 18:199. [PMID: 32404108 PMCID: PMC7222471 DOI: 10.1186/s12967-020-02360-6] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 05/02/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. METHODS We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. RESULTS mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 106/L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. CONCLUSION mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.
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Affiliation(s)
- Yi Zhang
- Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Peng Cui
- Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Hao-Cheng Zhang
- Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Hong-Long Wu
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Ming-Zhi Ye
- BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China
| | - Yi-Min Zhu
- Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Jing-Wen Ai
- Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China.
| | - Wen-Hong Zhang
- Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
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Samannodi M, Hansen M, Allana A, Hasbun R. Compliance with international guidelines in adults with encephalitis. J Clin Virol 2020; 127:104369. [PMID: 32315818 PMCID: PMC7194944 DOI: 10.1016/j.jcv.2020.104369] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/09/2020] [Accepted: 04/11/2020] [Indexed: 01/07/2023]
Abstract
Background Encephalitis is associated with significant neurological disability and mortality. Many guidelines are published for encephalitis management but compliance with them is unknown. Objectives To evaluate the appropriate management and compliance to the current guidelines in adults with encephalitis. Study design A retrospective multicenter study at 17 hospitals in the Greater Houston area from August 1, 2008 through September 30, 2017. All cases met the definition for possible or probable encephalitis as per the international encephalitis consortium guidelines. Results A total of 241 adults (age >17 years) with encephalitis were enrolled. The most common etiologies were unknown (41.9 %), viral (27.8 %) and autoimmune (21.2 %). An adverse clinical outcome was seen in 49 % with 12.4 % in hospital mortality. A high compliance with guidelines (>90 %) was only seen in obtaining a brain computerized tomography (CT) scan, blood cultures and cerebrospinal fluid (CSF) gram stain and culture. A CSF herpes virus simplex (HSV) polymerase chain reaction (PCR) was done in 84 % and only repeated in 14.2 % of patients with an initial negative result. Furthermore, only two-thirds of patients were started empirically on intravenous acyclovir and antibiotics. Evaluation for other etiologies were not uniformly performed: arboviral serologies (57.3 %), CSF anti-N-Methyl-d-Aspartate Receptor (NMDA) receptor antibody (35.7 %), and CSF varicella zoster virus (VZV) PCR (32 %). The highest yield for the tests were arboviral serologies (42 %), anti-NMDA antibodies (41.2 %) and VZV PCR (16.4 %). Conclusion The management of encephalitis as per current guidelines is suboptimal leading to underutilization of currently available diagnostic tests and empirical therapy.
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Affiliation(s)
- Mohammed Samannodi
- Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX, United States.
| | - Michael Hansen
- Department of Family Medicine and Community Medicine, Baylor College of Medicine, Houston, TX, United States
| | - Ambreen Allana
- Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX, United States
| | - Rodrigo Hasbun
- Department of Internal Medicine, UT Health McGovern Medical School, Houston, TX, United States
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