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1
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Maltsev D. Clinic-radiological classification of herpesviral encephalitis in humans (systematic review). J Neurovirol 2025:10.1007/s13365-025-01250-1. [PMID: 40253477 DOI: 10.1007/s13365-025-01250-1] [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: 01/30/2025] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 04/21/2025]
Abstract
The development of a comprehensive classification for herpesvirus encephalitis remains an urgent task. Distinct clinic-radiological forms of herpesvirus cerebral lesions have been characterized, including findings from histopathological studies. Differences among these forms have been demonstrated concerning key clinical and paraclinical parameters. The presented classification identifies several distinct forms of herpesvirus encephalitis: temporal, brainstem, limbic, diencephalic encephalitis, rhombencephalitis, leukoencephalitis, ventriculoencephalitis, diffuse glial micronodular encephalitis, subcortical and cortical encephalitis, cerebellitis, neonatal encephalitis. Additionally, the concepts of combined, coexisting and multimodal lesions are introduced to describe complex forms of herpesvirus neuroinfections. The use of the term "specific spectrum of herpesvirus cerebral lesions" is supported. Both the phenomena of specificity and universality are considered. Fundamental differences between the forms of herpesvirus encephalitis are highlighted with respect to their prevalence within the population, etiological factors, clinical manifestations, typical complications, recovery completeness, mortality rates, immune status. The distinctive diagnostic and therapeutic approaches required for each form of herpesvirus encephalitis are emphasized. The integration of this classification into clinical practice has the potential to optimize medical care for patients with herpesvirus encephalitis, enabling not only etiologically-oriented but also form-specific approaches to treatment.
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Affiliation(s)
- Dmytro Maltsev
- Laboratory of Immunology and Molecular Biology, Institute of Experimental and Clinical Medicine, O'Bogomolets National Medical University, 13, Shevchenka Av, Kyiv, 20122, Ukraine.
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2
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Mohamed AS, Jahani N, Li M, Shah M, Bruno A, Singh D. Autoimmune Rhombencephalitis as a Presentation of Post-COVID-19 Syndrome: A Case Report. Cureus 2025; 17:e79517. [PMID: 40135036 PMCID: PMC11936410 DOI: 10.7759/cureus.79517] [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] [Accepted: 02/23/2025] [Indexed: 03/27/2025] Open
Abstract
There has been a multitude of neurological sequelae associated with the 2019 SARS-CoV-2 outbreak. We describe a unique case of a 31-year-old individual who developed post-infectious autoimmune rhombencephalitis approximately two weeks after testing positive for coronavirus disease 2019 (COVID-19). Treatment with high-dose corticosteroids with four weeks of taper resulted in excellent clinical recovery without any relapse. Thus, our findings support the use of immunotherapy as a potential treatment in cases of post-COVID-19 autoimmune rhombencephalitis. Furthermore, this case highlights the importance of considering post-infectious COVID-19 sequelae as a differential diagnosis in patients presenting with rhombencephalitis in the appropriate clinical setting.
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Affiliation(s)
| | - Neesha Jahani
- Neurology, Augusta University Medical College of Georgia, Augusta, USA
| | - Mingyu Li
- Neurology, Augusta University Medical College of Georgia, Augusta, USA
| | - Manan Shah
- Neurology, Augusta University Medical College of Georgia, Augusta, USA
| | - Askiel Bruno
- Neurology, Augusta University Medical College of Georgia, Augusta, USA
| | - Dilip Singh
- Neurology, Augusta University Medical College of Georgia, Augusta, USA
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3
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Resman Rus K, Bosilj M, Triglav T, Jereb M, Zalaznik M, Klešnik M, Češljarac D, Matičič M, Avšič-Županc T, Rus T, Korva M. Metagenomic Sequencing for Diagnosing Listeria-Induced Rhombencephalitis in Patient and Contaminated Cheese Samples: A Case Report. Int J Mol Sci 2025; 26:655. [PMID: 39859368 PMCID: PMC11765671 DOI: 10.3390/ijms26020655] [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: 11/25/2024] [Revised: 01/08/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Among the various causes of rhomboencephalitis, Listeria monocytogenes infection is the most common. However, conventional microbiological methods often yield negative results, making diagnosis challenging and leading to extensive, often inconclusive, diagnostics. Advanced molecular techniques like metagenomic next-generation sequencing (mNGS) offer a powerful and efficient approach to pathogen identification. We present a case of life-threatening rhomboencephalitis in a 32-year-old immunocompetent patient where extensive microbiological, immunological, and biochemical tests were inconclusive. Given the patient's consumption of unpasteurized homemade cheese, neurolisteriosis was suspected, and mNGS was employed on clinical samples (CSF, serum, urine) and the food source to identify the pathogen. mNGS detected L. monocytogenes in both patient samples and the cheese. Mapping reads were distributed across the genome, with 18.9% coverage in clinical samples and 11.8% in the cheese sample. Additionally, the Listeriolysin (hlyA) gene was detected with 22.3% coverage in clinical samples and 12.3% in the food source, confirming neurolisteriosis. The patient fully recovered following antibiotic treatment. This case underscores the importance of mNGS in diagnosing CNS infections when conventional methods yield negative results, and supports its inclusion in diagnostic protocols for suspected neurolisteriosis, particularly when traditional methods prove inadequate.
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Affiliation(s)
- Katarina Resman Rus
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; (K.R.R.)
| | - Martin Bosilj
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; (K.R.R.)
| | - Tina Triglav
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; (K.R.R.)
| | - Matjaž Jereb
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Mateja Zalaznik
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Maša Klešnik
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Danilo Češljarac
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Mojca Matičič
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Tatjana Avšič-Županc
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; (K.R.R.)
| | - Tomaž Rus
- Department of Neurology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Misa Korva
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; (K.R.R.)
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4
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Zhang SY, Casanova JL. Genetic defects of brain immunity in childhood herpes simplex encephalitis. Nature 2024; 635:563-573. [PMID: 39567785 PMCID: PMC11822754 DOI: 10.1038/s41586-024-08119-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 09/25/2024] [Indexed: 11/22/2024]
Abstract
Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in humans. It is life-threatening and has a first peak of incidence in childhood, during primary infection. Children with HSE are not particularly prone to other infections, including HSV-1 infections of tissues other than the brain. About 8-10% of childhood cases are due to monogenic inborn errors of 19 genes, two-thirds of which are recessive, and most of which display incomplete clinical penetrance. Childhood HSE can therefore be sporadic but genetic, enabling new diagnostic and therapeutic approaches. In this Review, we examine essential cellular and molecular mechanisms of cell-intrinsic antiviral immunity in the brain that are disrupted in individuals with HSE. These mechanisms include both known (such as mutations in the TLR3 pathway) and previously unknown (such as the TMEFF1 restriction factor) antiviral pathways, which may be dependent (for example, IFNAR1) or independent (for example, through RIPK3) of type I interferons. They operate in cortical or brainstem neurons, and underlie forebrain and brainstem infections, respectively. Conversely, the most severe inborn errors of leukocytes, including a complete lack of myeloid and/or lymphoid blood cells, do not underlie HSE. Thus congenital defects in intrinsic immunity in brain-resident neurons that underlie HSE broaden natural host defences against HSV-1 from the leukocytes of the immune system to other cells in the organism.
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Affiliation(s)
- Shen-Ying Zhang
- St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.
- Paris Cité University, Imagine Institute, Paris, France.
| | - Jean-Laurent Casanova
- St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.
- Paris Cité University, Imagine Institute, Paris, France.
- Howard Hughes Medical Institute, New York, NY, USA.
- Department of Pediatrics, Necker Hospital for Sick Children, Paris, France.
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5
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Correale J, Solomon AJ, Cohen JA, Banwell BL, Gracia F, Gyang TV, de Bedoya FHD, Harnegie MP, Hemmer B, Jacob A, Kim HJ, Marrie RA, Mateen FJ, Newsome SD, Pandit L, Prayoonwiwat N, Sahraian MA, Sato DK, Saylor D, Shi FD, Siva A, Tan K, Viswanathan S, Wattjes MP, Weinshenker B, Yamout B, Fujihara K. Differential diagnosis of suspected multiple sclerosis: global health considerations. Lancet Neurol 2024; 23:1035-1049. [PMID: 39304243 DOI: 10.1016/s1474-4422(24)00256-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 05/14/2024] [Accepted: 06/04/2024] [Indexed: 09/22/2024]
Abstract
The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe.
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Affiliation(s)
- Jorge Correale
- Department of Neurology, Fleni, Buenos Aires, Argentina; Institute of Biological Chemistry and Biophysics, CONICET/University of Buenos Aires, Buenos Aires, Argentina.
| | - Andrew J Solomon
- Department of Neurological Sciences, Larner College of Medicine at the University of Vermont, Burlington, VT, USA
| | - Jeffrey A Cohen
- Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Brenda L Banwell
- Division of Child Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
| | - Fernando Gracia
- Hospital Santo Tomás, Panama City, Panama; Universidad Interamericana de Panamá, School of Medicine, Panama City, Panama
| | - Tirisham V Gyang
- Department of Neurology, The Ohio State University, Columbus, Ohio, USA
| | | | - Mary P Harnegie
- Cleveland Clinic Libraries, Cleveland Clinic, Cleveland, Ohio, USA
| | - Bernhard Hemmer
- Department of Neurology, Klinikum Rechts der Isar, School of Medicine and Health, Technical University of Munich, Munich Cluster for Systems Neurology, Munich, Germany
| | - Anu Jacob
- Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | - Ho Jin Kim
- Department of Neurology, National Cancer Center, Goyang, South Korea
| | - Ruth Ann Marrie
- Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Farrah J Mateen
- Department of Neurology, Massachusetts General Hospital, Harvard University, Boston, USA
| | - Scott D Newsome
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lekha Pandit
- Center for Advanced Neurological Research, KS Hedge Medical Academy, Nitte University, Mangalore, India
| | - Naraporn Prayoonwiwat
- Division of Neurology, Department of Medicine and Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Mohammad A Sahraian
- MS Research Center, Neuroscience Institute, Teheran University of Medical Sciences, Iran
| | - Douglas K Sato
- Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Deanna Saylor
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; University Teaching Hospital, Lusaka, Zambia
| | - Fu-Dong Shi
- Tianjin Medical University General Hospital, Tianjin, China; National Clinical Research Center for Neurological Disorders, Beijing Tiantan Hospital, Beijing, China
| | - Aksel Siva
- Istanbul University Cerrahpasa, School of Medicine, Department of Neurology, Clinical Neuroimmunology Unit and MS Clinic, Istanbul, Türkiye
| | - Kevin Tan
- Department of Neurology, National Neuroscience Institute, Singapore; Duke-NUS Medical School, Singapore
| | | | - Mike P Wattjes
- Department of Neuroradiology, Charité Berlin, Corporate Member of Freie Universität zu Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Brian Weinshenker
- Department of Neurology, University of Virginia, Charlottesville, VA, USA
| | - Bassem Yamout
- Neurology Institute, Harley Street Medical Center, Abu Dhabi, United Arab Emirates
| | - Kazuo Fujihara
- Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine and Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Japan.
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6
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Dubey P, Seth S, Rao P, Naphade P. Rhombencephalitis With Long Segment Transverse Myelitis: A Presentation With a Rare Etiology. Cureus 2024; 16:e69386. [PMID: 39411647 PMCID: PMC11473204 DOI: 10.7759/cureus.69386] [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: 07/08/2024] [Accepted: 09/14/2024] [Indexed: 10/19/2024] Open
Abstract
Rhombencephalitis is an inflammatory disease affecting the hindbrain (brainstem and cerebellum). The causes of rhombencephalitis can be divided into infections, autoimmune conditions, and paraneoplastic syndrome. Early onset rhombencephalitis is associated with demyelinating disorders or Epstein-Barr virus infection. Infections like Listeria and paraneoplastic disorders were seen in older individuals. Transverse myelitis includes pathobiological heterogeneous syndrome characterized by acute or subacute spinal cord dysfunction resulting in paraparesis, a sensory level, and autonomic (bladder, bowel, and sexual) impairment below the level. A lesion of the spinal cord where three or more vertebral segments are involved is called longitudinally extensive transverse myelitis (LETM). One of the most distinct causes of LETM is neuromyelitis optica spectrum disorder. Here, we describe a 34-year-old male who presented with quadriparesis, multiple cranial nerve palsies with sensory, bowel, and bladder involvement, along with altered sensorium with a preceding history of fever five days back. His magnetic resonance imaging (MRI) of the brain and spine was suggestive of rhombencephalitis with long-segment transverse myelitis. He later developed an intracranial hemorrhage during the hospital stay. His cerebrospinal fluid BioFire (BioFire Diagnostics, LCC, Salt Lake City, UT) was positive for herpes simplex virus 1.
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Affiliation(s)
- Prashant Dubey
- Department of Internal Medicine, Rohilkhand Medical College and Hospital, Bareilly, IND
| | - Seema Seth
- Department of Internal Medicine, Rohilkhand Medical College and Hospital, Bareilly, IND
| | - Prajwal Rao
- Department of Neurology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, IND
| | - Pravin Naphade
- Department of Neurology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, IND
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7
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Chan YH, Liu Z, Bastard P, Khobrekar N, Hutchison KM, Yamazaki Y, Fan Q, Matuozzo D, Harschnitz O, Kerrouche N, Nakajima K, Amin P, Yatim A, Rinchai D, Chen J, Zhang P, Ciceri G, Chen J, Dobbs K, Belkaya S, Lee D, Gervais A, Aydın K, Kartal A, Hasek ML, Zhao S, Reino EG, Lee YS, Seeleuthner Y, Chaldebas M, Bailey R, Vanhulle C, Lorenzo L, Boucherit S, Rozenberg F, Marr N, Mogensen TH, Aubart M, Cobat A, Dulac O, Emiroglu M, Paludan SR, Abel L, Notarangelo L, Longnecker R, Smith G, Studer L, Casanova JL, Zhang SY. Human TMEFF1 is a restriction factor for herpes simplex virus in the brain. Nature 2024; 632:390-400. [PMID: 39048830 PMCID: PMC11306101 DOI: 10.1038/s41586-024-07745-x] [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: 08/08/2022] [Accepted: 06/21/2024] [Indexed: 07/27/2024]
Abstract
Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.
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Affiliation(s)
- Yi-Hao Chan
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
| | - Zhiyong Liu
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Paul Bastard
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Paris Cité University, Imagine Institute, Paris, France
- Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Noopur Khobrekar
- The Center for Stem Cell Biology & Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Kennen M Hutchison
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Yasuhiro Yamazaki
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Qing Fan
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Daniela Matuozzo
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Oliver Harschnitz
- The Center for Stem Cell Biology & Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA
- Human Technopole, Milan, Italy
| | - Nacim Kerrouche
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Koji Nakajima
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Param Amin
- The Center for Stem Cell Biology & Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Ahmad Yatim
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Darawan Rinchai
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Jie Chen
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Peng Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Gabriele Ciceri
- The Center for Stem Cell Biology & Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Jia Chen
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Kerry Dobbs
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Serkan Belkaya
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
| | - Danyel Lee
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Adrian Gervais
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Kürşad Aydın
- Department of Pediatric Neurology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey
| | - Ayse Kartal
- Child Neurology Department, Selcuk University, Konya, Turkey
| | - Mary L Hasek
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Shuxiang Zhao
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Eduardo Garcia Reino
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Yoon Seung Lee
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Yoann Seeleuthner
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Matthieu Chaldebas
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | - Rasheed Bailey
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
| | | | - Lazaro Lorenzo
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Soraya Boucherit
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Flore Rozenberg
- Laboratory of Virology, Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Hospital, Paris, France
| | - Nico Marr
- Research Branch, Sidra Medicine, Doha, Qatar
| | - Trine H Mogensen
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark
| | - Mélodie Aubart
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Pediatric Neurology Department, Necker Hospital for Sick Children, Paris-City University, Paris, France
| | - Aurélie Cobat
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Olivier Dulac
- Department of Pediatric Neurology, Necker Hospital for Sick Children, AP-HP, Paris, France
| | - Melike Emiroglu
- Department of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Søren R Paludan
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark
- Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Laurent Abel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
- Paris Cité University, Imagine Institute, Paris, France
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
| | - Luigi Notarangelo
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Richard Longnecker
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Greg Smith
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Lorenz Studer
- The Center for Stem Cell Biology & Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
- Paris Cité University, Imagine Institute, Paris, France.
- Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
- Howard Hughes Medical Institute, New York, NY, USA.
| | - Shen-Ying Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
- Paris Cité University, Imagine Institute, Paris, France.
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
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8
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T AM, Singh B, Rupali P. Central nervous system infections in the tropics. Curr Opin Infect Dis 2024; 37:201-210. [PMID: 38529912 DOI: 10.1097/qco.0000000000001015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
PURPOSE OF REVIEW Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. RECENT FINDINGS In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. SUMMARY A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.
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Affiliation(s)
| | - Bhagteshwar Singh
- Tropical and Infectious Diseases Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom; Institute of Infection Veterinary & Ecological Sciences, University of Liverpool, Liverpool, United Kingdom; Department of Infectious Diseases
| | - Priscilla Rupali
- Department of Infectious Diseases, Christian Medical College, Vellore, India
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9
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Sanvito F, Pichiecchio A, Paoletti M, Rebella G, Resaz M, Benedetti L, Massa F, Morbelli S, Caverzasi E, Asteggiano C, Businaro P, Masciocchi S, Castellan L, Franciotta D, Gastaldi M, Roccatagliata L. Autoimmune encephalitis: what the radiologist needs to know. Neuroradiology 2024; 66:653-675. [PMID: 38507081 PMCID: PMC11031487 DOI: 10.1007/s00234-024-03318-x] [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: 11/15/2023] [Accepted: 02/20/2024] [Indexed: 03/22/2024]
Abstract
Autoimmune encephalitis is a relatively novel nosological entity characterized by an immune-mediated damage of the central nervous system. While originally described as a paraneoplastic inflammatory phenomenon affecting limbic structures, numerous instances of non-paraneoplastic pathogenesis, as well as extra-limbic involvement, have been characterized. Given the wide spectrum of insidious clinical presentations ranging from cognitive impairment to psychiatric symptoms or seizures, it is crucial to raise awareness about this disease category. In fact, an early diagnosis can be dramatically beneficial for the prognosis both to achieve an early therapeutic intervention and to detect a potential underlying malignancy. In this scenario, the radiologist can be the first to pose the hypothesis of autoimmune encephalitis and refer the patient to a comprehensive diagnostic work-up - including clinical, serological, and neurophysiological assessments.In this article, we illustrate the main radiological characteristics of autoimmune encephalitis and its subtypes, including the typical limbic presentation, the features of extra-limbic involvement, and also peculiar imaging findings. In addition, we review the most relevant alternative diagnoses that should be considered, ranging from other encephalitides to neoplasms, vascular conditions, and post-seizure alterations. Finally, we discuss the most appropriate imaging diagnostic work-up, also proposing a suggested MRI protocol.
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Affiliation(s)
- Francesco Sanvito
- Unit of Radiology, Department of Clinical, Surgical, Diagnostic, and Paediatric Sciences, University of Pavia, Viale Camillo Golgi, 19, 27100, Pavia, Italy.
- UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California Los Angeles, Los Angeles, CA, USA.
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
| | - Anna Pichiecchio
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Advanced Imaging and Artificial Intelligence Center, Department of Neuroradiology, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Matteo Paoletti
- Advanced Imaging and Artificial Intelligence Center, Department of Neuroradiology, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Giacomo Rebella
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Martina Resaz
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Luana Benedetti
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Federico Massa
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132, Genoa, Italy
| | - Silvia Morbelli
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
- Department of Health Sciences (DISSAL), University of Genoa, Via Antonio Pastore 1, 16132, Genoa, Italy
| | - Eduardo Caverzasi
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Advanced Imaging and Artificial Intelligence Center, Department of Neuroradiology, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Carlo Asteggiano
- Advanced Imaging and Artificial Intelligence Center, Department of Neuroradiology, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Pietro Businaro
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Stefano Masciocchi
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Lucio Castellan
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Diego Franciotta
- Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Matteo Gastaldi
- Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | - Luca Roccatagliata
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy
- Department of Health Sciences (DISSAL), University of Genoa, Via Antonio Pastore 1, 16132, Genoa, Italy
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10
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Song Z, Ding Y, Sim N, Yun HJ, Feng J, Gu P, Geng X. Vestibular function is associated with immune inflammatory response. Rev Neurosci 2024; 35:293-301. [PMID: 38158886 DOI: 10.1515/revneuro-2023-0114] [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: 09/19/2023] [Accepted: 11/10/2023] [Indexed: 01/03/2024]
Abstract
Association between vestibular function and immune inflammatory response has garnered increasing interest. Immune responses can lead to anatomical or functional alterations of the vestibular system, and inflammatory reactions may impair hearing and balance. Vestibular disorders comprise a variety of conditions, such as vestibular neuritis, benign paroxysmal positional vertigo, Meniere's disease, vestibular migraine, posterior circulation ischemia, and bilateral vestibular disease. Moreover, some patients with autoimmune diseases develop vestibulocochlear symptom. This paper offers an overview of prevalent vestibular diseases and discusses associations between vestibular dysfunction and immune diseases.
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Affiliation(s)
- Zhaohui Song
- Department of Neurology and the Stroke Intervention and Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, No. 82 Xinhua South Road, 101149, Tongzhou District, Beijing, China
| | - Yuchuan Ding
- Department of Neurosurgery, Wayne State University School of Medicine, 550 E Canfield, 48201, Detroit, MI, USA
| | - Nathan Sim
- Department of Neurosurgery, Wayne State University School of Medicine, 550 E Canfield, 48201, Detroit, MI, USA
| | - Ho Jun Yun
- Department of Neurosurgery, Wayne State University School of Medicine, 550 E Canfield, 48201, Detroit, MI, USA
| | - Jing Feng
- Department of Neurology and the Stroke Intervention and Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, No. 82 Xinhua South Road, 101149, Tongzhou District, Beijing, China
| | - Pan Gu
- Department of Neurology and the Stroke Intervention and Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, No. 82 Xinhua South Road, 101149, Tongzhou District, Beijing, China
| | - Xiaokun Geng
- Department of Neurology and the Stroke Intervention and Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, No. 82 Xinhua South Road, 101149, Tongzhou District, Beijing, China
- Department of Neurosurgery, Wayne State University School of Medicine, 550 E Canfield, 48201, Detroit, MI, USA
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, No. 82 Xinhua South Road, 101149, Tongzhou District, Beijing, China
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11
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Kachuei M, Zare R, Sayyahfar S, Khalili M, Movahedi H, Naghshbandi M, Eghdami S. An unusual imaging presentation of pediatric bacterial meningoencephalitis: a case-report study. Ann Med Surg (Lond) 2024; 86:1739-1744. [PMID: 38463079 PMCID: PMC10923334 DOI: 10.1097/ms9.0000000000001749] [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: 12/21/2023] [Accepted: 01/11/2024] [Indexed: 03/12/2024] Open
Abstract
Background Bacterial meningoencephalitis is a serious infection affecting the brain and its surrounding membranes. While imaging studies play a crucial role in diagnosing this condition, the typical radiological findings are well-documented. However, this case report describes an unusual imaging presentation that deviates from the expected patterns, emphasizing the need for awareness of such variations. Case presentation A 7-year-old female with no prior medical history was referred to our hospital with fever, seizure, and loss of Consciousness. She had mild flu a week before admission. The duration of seizure episodes were 2-3 min, with tonic-clonic uncontrollable jerky movements. Brudzinski and Kernig signs were positive and plantar reflex was upward bilaterally in the physical examination. The computed tomography (CT) scan showed brain ventriculomegaly/hydrocephalus, and MRI findings indicated multiple foci located at cerebellum, basal ganglia, and thalamus alongside intensely restricted diffusion of the layering debris, suggesting pyogenic ventriculitis. Cerebrospinal fluid (CSF) analysis showed severe hypoglycorrhachia, despite non-significant increase of protein. The patient was undergone antibiotic therapy with ceftriaxone, vancomycin and rifampin, resulting in normalization of CSF values. Conclusion This case report highlights the importance of recognizing and interpreting unusual imaging presentations of bacterial meningoencephalitis in paediatric patients. It emphasizes the need for a comprehensive diagnostic approach, including clinical evaluation, laboratory tests, and imaging studies, to ensure accurate diagnosis and appropriate management of this potentially life-threatening condition. Further research and awareness of atypical imaging findings are warranted to enhance our understanding and improve patient outcomes.
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Affiliation(s)
- Maryam Kachuei
- Firoozabadi Clinical Research Development Unit (FACRDU), School of Medicine, Iran University of Medical Sciences
| | - Ramin Zare
- Firoozabadi Clinical Research Development Unit (FACRDU), School of Medicine, Iran University of Medical Sciences
| | - Shirin Sayyahfar
- Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, School of Medicine, Iran University of Medical Sciences
| | - Mitra Khalili
- Department of Radiology, Shahid Beheshti University of Medical Sciences
| | | | | | - Shayan Eghdami
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
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12
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García de Andoin Sojo C, Gómez Muga JJ, Aza Martínez I, Antón Méndez L, Fornell Pérez R. Inflammatory lesions of the brainstem: Keys for the diagnosis by MRI. RADIOLOGIA 2024; 66:32-46. [PMID: 38365353 DOI: 10.1016/j.rxeng.2023.01.010] [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: 09/20/2022] [Accepted: 01/15/2023] [Indexed: 02/18/2024]
Abstract
OBJECTIVE To describe the magnetic resonance imaging (MRI) findings for the most common inflammatory and immune-mediated diseases that involve the brainstem. CONCLUSION Inflammatory lesions involving the brainstem are associated with a wide range of autoimmune, infectious, and paraneoplastic syndromes, making the differential diagnosis complex. Being familiar with these entities, their clinical characteristics, and their manifestations on MRI, especially the number of lesions, their shape and extension, and their appearance in different sequences, is useful for orienting the radiological diagnosis.
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Affiliation(s)
| | - J J Gómez Muga
- Servicio de Radiodiagnóstico, Hospital Universitario Basurto, Bilbao, Spain
| | - I Aza Martínez
- Servicio de Radiodiagnóstico, Hospital Universitario Basurto, Bilbao, Spain
| | - L Antón Méndez
- Servicio de Radiodiagnóstico, Hospital Universitario Basurto, Bilbao, Spain
| | - R Fornell Pérez
- Servicio de Radiodiagnóstico, Hospital Universitario Basurto, Bilbao, Spain
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13
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Caliskan E, Sager SG, Yukselmis U, Kilic AK, Gunbey HP. Coexistence of longitudinally extensive transverse myelitis and diffuse midline glioma in the brainstem in an adolescent boy with acute flaccid paralysis. Childs Nerv Syst 2024; 40:227-232. [PMID: 37737897 DOI: 10.1007/s00381-023-06163-0] [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: 07/05/2023] [Accepted: 09/18/2023] [Indexed: 09/23/2023]
Abstract
We present the case of a previously healthy 13-year-old boy who was admitted to the emergency department with acute flaccid paralysis. Magnetic resonance imaging revealed radiological evidence of longitudinally extensive transverse myelitis. Additionally, homogeneous T2 signal increase was observed in the pons and medulla oblongata, initially indicating brainstem encephalitis. Subsequent evaluations confirmed a coexistence of diffuse midline glioma (DMG) in the brain stem alongside acute transverse myelitis (ATM). Children with ATM generally have a more favorable prognosis than adults. However, despite the implementation of advanced treatment methods, the patient's quadriplegia did not improve and resulted in spinal cord sequela atrophy. DMG exhibits an aggressive growth pattern and lacks a known curative treatment. This case represents an exceedingly rare synchronous occurrence of aggressive conditions, underscoring the importance of raising awareness among physicians. Furthermore, we aim to discuss the radiologic differential diagnosis, as this is the first documented instance in the literature.
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Affiliation(s)
- Emine Caliskan
- Department of Pediatric Radiology, Kartal Dr. Lutfi Kirdar City Hospital, University of Health Sciences, D-100 Güney Yanyol, Cevizli Mevkii, No:47, 34865, Kartal, Istanbul, Turkey.
| | - Safiye Gunes Sager
- Department of Pediatric Neurology, Kartal Dr. Lutfi Kirdar City Hospital, University of Health Sciences, D-100 Güney Yanyol, Cevizli Mevkii, No:47, 34865, Kartal, Istanbul, Turkey
| | - Ufuk Yukselmis
- Department of Pediatric Intensive Care, Kartal Dr. Lutfi Kirdar City Hospital, University of Health Sciences, D-100 Güney Yanyol, Cevizli Mevkii, No:47, 34865, Kartal, Istanbul, Turkey
| | - Ahmet Kasim Kilic
- Department of Neurology, Kartal Dr. Lutfi Kirdar City Hospital, University of Health Sciences, D-100 Güney Yanyol, Cevizli Mevkii, No:47, 34865, Kartal, Istanbul, Turkey
| | - Hediye Pınar Gunbey
- Department Radiology, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, D-100 Güney Yanyol, Cevizli Mevkii, No:47, 34865, Kartal Istanbul, Turkey
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14
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Silva TL, Corbiceiro WCH, Corrêa DG. Rhombencephalitis Caused by Cytomegalovirus. Can J Neurol Sci 2023; 50:905-906. [PMID: 36522675 DOI: 10.1017/cjn.2022.342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Thallys Leal Silva
- Department of Radiology, Federal Fluminense University, Niterói, RJ, Brazil
| | | | - Diogo Goulart Corrêa
- Department of Radiology, Federal Fluminense University, Niterói, RJ, Brazil
- Department of Radiology, Clínica de Diagnóstico por Imagem (CDPI)/DASA, Rio de Janeiro, RJ, Brazil
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15
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Iyigundogdu I, Gedik E, Derle E, Kibaroglu S. Listeria Rhombencephalitis and Infratentorial Brain Abcesses ın a Young Adult with Stroke Like Presentation. Neurol India 2023; 71:1263-1265. [PMID: 38174473 DOI: 10.4103/0028-3886.391395] [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] [Indexed: 01/05/2024]
Abstract
Rhombencephalitis refers to the inflammation of rhombencephalon, and Listeria monocytogenes is one of the causes of infectious rhombencephalitis. Listeria rhombencephalitis is a rare and severe infection with high mortality and morbidity. As the disease can present with a variety of neurological symptoms and nonspecific laboratory tests, it can easily be misdiagnosed. Sudden onset of neurological signs without fever can resemble stroke. Magnetic resonance imaging can be useful in patients for confirmation of the diagnosis and during the follow-up. Early diagnosis and treatment are especially important for improvement of the outcomes. Here we report a case with stroke-like presentation that was diagnosed as Listeria rhombencephalitis in follow-up and present the serial brain magnetic resonance imaging features.
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Affiliation(s)
- Ilkin Iyigundogdu
- Department of Neurology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Ender Gedik
- Department of Anesthesiology and Reanimation, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Eda Derle
- Department of Neurology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Seda Kibaroglu
- Department of Neurology, Faculty of Medicine, Baskent University, Ankara, Turkey
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16
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Pinto SN, Liu CSJ, Nelson MD, Bluml S, Livingston D, Tamrazi B. Neuroimaging of complications arising after CD19 chimeric antigen receptor T-cell therapy: A review. J Neuroimaging 2023; 33:703-715. [PMID: 37327044 DOI: 10.1111/jon.13138] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/02/2023] [Accepted: 06/05/2023] [Indexed: 06/17/2023] Open
Abstract
Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B-cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood-brain barrier and cause an immune effector cell-associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood-brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T-cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T-cell therapy using illustrative cases from two tertiary care institutions.
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Affiliation(s)
- Soniya N Pinto
- Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Chia-Shang J Liu
- Division of Neuroradiology, Department of Radiology, Children's Hospital of Los Angeles, Los Angeles, California, USA
| | - Marvin D Nelson
- Division of Neuroradiology, Department of Radiology, Children's Hospital of Los Angeles, Los Angeles, California, USA
| | - Stefan Bluml
- Division of Neuroradiology, Department of Radiology, Children's Hospital of Los Angeles, Los Angeles, California, USA
| | - David Livingston
- Resident, Department of Radiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Benita Tamrazi
- Division of Neuroradiology, Department of Radiology, Children's Hospital of Los Angeles, Los Angeles, California, USA
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17
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Consoli S, Dono F, Evangelista G, Corniello C, Onofrj M, Thomas A, Sensi SL. Case Report: Brain tumor's pitfalls: two cases of high-grade brain tumors mimicking autoimmune encephalitis with positive onconeuronal antibodies. Front Oncol 2023; 13:1254674. [PMID: 37692853 PMCID: PMC10484219 DOI: 10.3389/fonc.2023.1254674] [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: 07/07/2023] [Accepted: 07/18/2023] [Indexed: 09/12/2023] Open
Abstract
Background Glioblastoma (GBM) is the most common primary brain tumor in adulthood. Initial diagnosis is generally based on clinical and MRI findings, which may be misinterpreted as other neurological pictures, including autoimmune encephalitis (AE). AE is a heterogeneous group of neuroinflammatory diseases due to the presence of auto-antibodies targeting antigens on neuronal synaptic or cell surface. In the present report, we describe two peculiar cases of GBM initially misdiagnosed as AE, focusing on the diagnostic pitfalls and the treatment strategies. Methods We report the case of two patients with high-grade brain tumors, initially misdiagnosed and treated for AE. Clinical, laboratory, and neuroradiological data are discussed in terms of differential diagnosis between AE and GBM. Results The presence of atypical brain MRI findings and the unresponsiveness to immunosuppressive treatment are major red flags in the differential diagnosis between AE and GBM. In these cases, a brain biopsy is necessary to confirm the diagnosis. Conclusions Atypical brain tumor presentation causes a diagnostic and therapeutic delay. A positive onconeural autoantibodies result should always be interpreted cautiously, considering the possibility of a false-positive test. A brain biopsy is mandatory for a definite diagnosis.
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Affiliation(s)
- Stefano Consoli
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
- Epilepsy Center, “SS Annunziata” Hospital, Chieti, Italy
| | - Fedele Dono
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
- Epilepsy Center, “SS Annunziata” Hospital, Chieti, Italy
| | - Giacomo Evangelista
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
- Epilepsy Center, “SS Annunziata” Hospital, Chieti, Italy
| | - Clarissa Corniello
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
- Epilepsy Center, “SS Annunziata” Hospital, Chieti, Italy
| | - Marco Onofrj
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
| | - Astrid Thomas
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
| | - Stefano L. Sensi
- Department of Neuroscience, Imaging and Clinical Science, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
- Behavioral Neurology and Molecular Neurology Units, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy
- Institute for Advanced Biomedical Technologies, University of Chieti-Pescara, Chieti, Italy
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18
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Surabotsophon M, Laohachavalit P, Ponglikitmongkol S, Chuncharunee S, Sudsang T, Thanachartwet V, Sahassananda D, Hunsawong T, Klungthong C, Fernandez S, Kalayanarooj S, Desakorn V, Leelasetakul S. Secondary dengue serotype 1 infection causing dengue shock syndrome with rhombencephalitis and bleeding associated with refractory thrombocytopenia: A case report. Heliyon 2023; 9:e17419. [PMID: 37441400 PMCID: PMC10333608 DOI: 10.1016/j.heliyon.2023.e17419] [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: 05/26/2022] [Revised: 06/09/2023] [Accepted: 06/16/2023] [Indexed: 07/15/2023] Open
Abstract
Background Dengue has a wide spectrum of manifestations, from an asymptomatic condition to dengue shock syndrome. Extensive plasma leakage, severe bleeding, or both, could lead to dengue shock syndrome, a common cause of death in dengue-infected patients. Thrombocytopenia is a common laboratory finding in dengue, which correlates with the disease severity and rapidly resolves during the recovery phase. Therefore, refractory thrombocytopenia is rare in patients with dengue. Rhombencephalitis is an inflammatory disease affecting the hindbrain, rarely associated with dengue. We report the second case of dengue-associated rhombencephalitis, wherein the patient developed dengue shock syndrome and severe bleeding associated with refractory thrombocytopenia. Case report A 47-year-old Thai female with secondary dengue serotype 1 infection developed dengue shock syndrome with rhombencephalitis, manifested as altered sensorium and status epilepticus in the critical phase. Cerebrospinal fluid analysis showed pleocytosis with predominantly mononuclear cells and high protein levels. Magnetic resonance imaging of the brain showed multifocal brain signal abnormalities involving the medulla oblongata, pons, midbrain, bilateral hippocampi, thalami, posterior limb of internal capsules, external capsules, and deep hemispheric white matter. The patient had partial neurological recovery following rhombencephalitis for one month. During the recovery phase, severe bleeding with refractory thrombocytopenia and acute kidney injury were observed. Methylprednisolone with eltrombopag was administered, which resulted in an increased the platelet count, cessation of bleeding and recovery of kidney function within 4 days. Conclusions Dengue is a potential cause of rhombencephalitis. Dengue-associated rhombencephalitis develops during the critical phase, with only partial neurological recovery. However, severe bleeding and refractory thrombocytopenia were also observed during the recovery phase. Methylprednisolone with a thrombopoietin receptor agonist could be an effective treatment for increasing platelet count and stopping bleeding in dengue.
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Affiliation(s)
- Manoon Surabotsophon
- Pulmonary and Critical Care Unit, Department of Medicine, Ramkhamhaeng Hospital, Bangkok 10240, Thailand
| | - Poonsak Laohachavalit
- Endocrine Unit, Department of Medicine, Ramkhamhaeng Hospital, Bangkok 10240, Thailand
| | | | - Suporn Chuncharunee
- Division of Haematology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Thanwa Sudsang
- Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Vipa Thanachartwet
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Duangjai Sahassananda
- Information Technology Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Taweewun Hunsawong
- Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS) Bangkok 10400, Thailand
| | - Chonticha Klungthong
- Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS) Bangkok 10400, Thailand
| | - Stefan Fernandez
- Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS) Bangkok 10400, Thailand
| | - Siripen Kalayanarooj
- Dengue Center of Excellence, Queen Sirikit National Institute of Child Health, Ministry of Public Health (MOPH), Bangkok 10400, Thailand
| | - Varunee Desakorn
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
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Roy S, Barreras P, Pardo CA, Graves JS, Zamvil SS, Newsome SD. Relapsing Encephalomyelitis After COVID-19 Infection and Vaccination: From the National MS Society Case Conference Proceedings. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2023; 10:10/3/e200112. [PMID: 37015826 PMCID: PMC10074377 DOI: 10.1212/nxi.0000000000200112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 02/09/2023] [Indexed: 04/06/2023]
Abstract
Prior case studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines may unmask CNS neuroinflammatory conditions. We present a case of relapsing steroid-responsive encephalomyelitis after SARS-CoV-2 infection and subsequent COVID-19 vaccination. We also characterize the frequency of CNS neuroinflammatory events reported in the literature after both SARS-CoV-2 infection and COVID-19 vaccination.
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Affiliation(s)
- Shuvro Roy
- From the Department of Neurology (S.R., P.B., C.A.P., S.D.N.), Johns Hopkins School of Medicine; Department of Neurology (J.S.G.), University of California San Diego School of Medicine; and Department of Neurology (S.S.Z.), University of California San Francisco School of Medicine
| | - Paula Barreras
- From the Department of Neurology (S.R., P.B., C.A.P., S.D.N.), Johns Hopkins School of Medicine; Department of Neurology (J.S.G.), University of California San Diego School of Medicine; and Department of Neurology (S.S.Z.), University of California San Francisco School of Medicine
| | - Carlos A Pardo
- From the Department of Neurology (S.R., P.B., C.A.P., S.D.N.), Johns Hopkins School of Medicine; Department of Neurology (J.S.G.), University of California San Diego School of Medicine; and Department of Neurology (S.S.Z.), University of California San Francisco School of Medicine
| | - Jennifer S Graves
- From the Department of Neurology (S.R., P.B., C.A.P., S.D.N.), Johns Hopkins School of Medicine; Department of Neurology (J.S.G.), University of California San Diego School of Medicine; and Department of Neurology (S.S.Z.), University of California San Francisco School of Medicine
| | - Scott S Zamvil
- From the Department of Neurology (S.R., P.B., C.A.P., S.D.N.), Johns Hopkins School of Medicine; Department of Neurology (J.S.G.), University of California San Diego School of Medicine; and Department of Neurology (S.S.Z.), University of California San Francisco School of Medicine
| | - Scott D Newsome
- From the Department of Neurology (S.R., P.B., C.A.P., S.D.N.), Johns Hopkins School of Medicine; Department of Neurology (J.S.G.), University of California San Diego School of Medicine; and Department of Neurology (S.S.Z.), University of California San Francisco School of Medicine.
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20
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Regner-Nelke L, Ruck T, Meuth SG. [Meningitis in the Emergency Room]. Anasthesiol Intensivmed Notfallmed Schmerzther 2023; 58:322-334. [PMID: 37192640 DOI: 10.1055/a-2077-6971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
AbstractMeningitis describes an inflammation of the meninges of the brain and spinal cord, which, depending on the etiology, can be a serious disease with high lethality. The suspicion of
meningitis therefore requires rapid and adept action. In this paper, we explain the diagnostic and therapeutic approach to suspected meningitis in the emergency department.
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21
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Liu Z, Garcia Reino EJ, Harschnitz O, Guo H, Chan YH, Khobrekar NV, Hasek ML, Dobbs K, Rinchai D, Materna M, Matuozzo D, Lee D, Bastard P, Chen J, Lee YS, Kim SK, Zhao S, Amin P, Lorenzo L, Seeleuthner Y, Chevalier R, Mazzola L, Gay C, Stephan JL, Milisavljevic B, Boucherit S, Rozenberg F, Perez de Diego R, Dix RD, Marr N, Béziat V, Cobat A, Aubart M, Abel L, Chabrier S, Smith GA, Notarangelo LD, Mocarski ES, Studer L, Casanova JL, Zhang SY. Encephalitis and poor neuronal death-mediated control of herpes simplex virus in human inherited RIPK3 deficiency. Sci Immunol 2023; 8:eade2860. [PMID: 37083451 PMCID: PMC10337828 DOI: 10.1126/sciimmunol.ade2860] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 03/30/2023] [Indexed: 04/22/2023]
Abstract
Inborn errors of TLR3-dependent type I IFN immunity in cortical neurons underlie forebrain herpes simplex virus-1 (HSV-1) encephalitis (HSE) due to uncontrolled viral growth and subsequent cell death. We report an otherwise healthy patient with HSE who was compound heterozygous for nonsense (R422*) and frameshift (P493fs9*) RIPK3 variants. Receptor-interacting protein kinase 3 (RIPK3) is a ubiquitous cytoplasmic kinase regulating cell death outcomes, including apoptosis and necroptosis. In vitro, the R422* and P493fs9* RIPK3 proteins impaired cellular apoptosis and necroptosis upon TLR3, TLR4, or TNFR1 stimulation and ZBP1/DAI-mediated necroptotic cell death after HSV-1 infection. The patient's fibroblasts displayed no detectable RIPK3 expression. After TNFR1 or TLR3 stimulation, the patient's cells did not undergo apoptosis or necroptosis. After HSV-1 infection, the cells supported excessive viral growth despite normal induction of antiviral IFN-β and IFN-stimulated genes (ISGs). This phenotype was, nevertheless, rescued by application of exogenous type I IFN. The patient's human pluripotent stem cell (hPSC)-derived cortical neurons displayed impaired cell death and enhanced viral growth after HSV-1 infection, as did isogenic RIPK3-knockout hPSC-derived cortical neurons. Inherited RIPK3 deficiency therefore confers a predisposition to HSE by impairing the cell death-dependent control of HSV-1 in cortical neurons but not their production of or response to type I IFNs.
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Affiliation(s)
- Zhiyong Liu
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Eduardo J Garcia Reino
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Oliver Harschnitz
- The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY, USA
- Human Technopole, Viale Rita Levi-Montalcini, Milan, Italy
| | - Hongyan Guo
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, GA, USA
- School of Medicine, Atlanta, GA, USA
- Louisiana State University Health Sciences Center at Shreveport (LSUHSC-S), Shreveport, LA, USA
| | - Yi-Hao Chan
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Noopur V Khobrekar
- The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Mary L Hasek
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Kerry Dobbs
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Darawan Rinchai
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Marie Materna
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Daniela Matuozzo
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Danyel Lee
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Paul Bastard
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
- Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France
| | - Jie Chen
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Yoon Seung Lee
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | | | - Shuxiang Zhao
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Param Amin
- The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Lazaro Lorenzo
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Yoann Seeleuthner
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Remi Chevalier
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Laure Mazzola
- Department of Pediatrics, Hôpital Nord, Saint-Etienne, Paris, France
| | - Claire Gay
- Department of Pediatrics, Hôpital Nord, Saint-Etienne, Paris, France
| | | | - Baptiste Milisavljevic
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
| | - Soraya Boucherit
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Flore Rozenberg
- Laboratory of Virology, Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Hospital, Paris, France
| | - Rebeca Perez de Diego
- Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain
- Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain
- Interdepartmental Group of Immunodeficiencies, Madrid, Spain
| | - Richard D Dix
- Viral Immunology Center, Department of Biology, Georgia State University, Atlanta, GA, USA
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
| | - Nico Marr
- Research Branch, Sidra Medicine, Doha, Qatar
- Institute of Translational Immunology, Brandenburg Medical School, Brandenburg an der Havel, Germany
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Vivien Béziat
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Aurelie Cobat
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Mélodie Aubart
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Pediatric Neurology Department, Necker Hospital for Sick Children, APHP, Paris City University, Paris, France
| | - Laurent Abel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
| | - Stephane Chabrier
- Department of Pediatrics, Hôpital Nord, Saint-Etienne, Paris, France
| | - Gregory A Smith
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Luigi D Notarangelo
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Edward S Mocarski
- Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, GA, USA
| | - Lorenz Studer
- The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY, USA
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
- Department of Pediatrics, Necker Hospital for Sick Children, Paris, France
- Howard Hughes Medical Institute, New York, NY, USA
| | - Shen-Ying Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France
- Paris City University, Imagine Institute, Paris, France
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22
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Shimizu H, Imoto H, Hara S, Nishioka H. Listeria rhombencephalitis mimicking stroke in a patient with giant cell arteritis. J Infect Chemother 2023; 29:703-706. [PMID: 36996936 DOI: 10.1016/j.jiac.2023.03.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 02/21/2023] [Accepted: 03/22/2023] [Indexed: 03/30/2023]
Abstract
Listeria monocytogenes sometimes causes central nervous system infections. However, rhombencephalitis is a rare form of L. monocytogenes infection. Its clinical symptoms and magnetic resonance imaging (MRI) findings are often similar to those of vertebrobasilar stroke. We present the case of a 79-year-old woman with Listeria rhombencephalitis presenting with rhinorrhea and productive cough. She had giant cell arteritis (GCA) treated with prednisolone and methotrexate. She was admitted for loss of appetite, rhinorrhea, and productive cough. These symptoms were alleviated without specific treatment; however, she suddenly developed multiple cranial nerve palsies, and MRI showed hyperintense signals on diffusion-weighted imaging and hypointense signals on apparent diffusion coefficient in the brainstem. Ischemic stroke due to exacerbation of GCA was suspected, and treatment with intravenous methylprednisolone was initiated; however, seizures occurred, and a lumbar puncture was performed. Cerebrospinal fluid and blood cultures revealed L. monocytogenes, and she was diagnosed with Listeria rhombencephalitis. Although antibiotic treatment was continued, the patient died. Thus, when patients with rhinorrhea or productive cough develop sudden cranial nerve palsy, Listeria rhombencephalitis should be considered as a differential diagnosis, and lumbar puncture should be performed.
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23
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Inborn Errors of Immunity Predisposing to Herpes Simplex Virus Infections of the Central Nervous System. Pathogens 2023; 12:pathogens12020310. [PMID: 36839582 PMCID: PMC9961685 DOI: 10.3390/pathogens12020310] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 02/16/2023] Open
Abstract
Herpesvirus infections can lead to a number of severe clinical manifestations, particularly when involving the central nervous system (CNS), causing encephalitis and meningitis. However, understanding of the host factors conferring increased susceptibility to these diseases and their complications remains incomplete. Previous studies have uncovered defects in the innate Toll-like receptor 3 pathway and production of type I interferon (IFN-I) in children and adults that predispose them to herpes simplex encephalitis. More recently, there is accumulating evidence for an important role of IFN-independent cell-autonomous intrinsic mechanisms, including small nucleolar RNAs, RNA lariat metabolism, and autophagy, in restricting herpesvirus replication and conferring protection against CNS infection. The present review first describes clinical manifestations of HSV infection with a focus on neurological complications and then summarizes the host-pathogen interactions and innate immune pathways responsible for sensing herpesviruses and triggering antiviral responses and immunity. Next, we review the current landscape of inborn errors of immunity and the underlying genetic defects and disturbances of cellular immune pathways that confer increased susceptibility to HSV infection in CNS. Ultimately, we discuss some of the present outstanding unanswered questions relating to inborn errors of immunity and HSV CNS infection together with some perspectives and future directions for research in the pathogenesis of these severe diseases in humans.
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24
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García de Andoin Sojo C, Gómez Muga J, Aza Martínez I, Antón Méndez L, Fornell Pérez R. Lesiones inflamatorias del troncoencéfalo: claves diagnósticas en RM. RADIOLOGIA 2023. [DOI: 10.1016/j.rx.2023.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
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25
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Rhombencephalitis in Pregnancy-A Challenging Case of Probable Listeria Infection. Life (Basel) 2022; 12:life12101600. [PMID: 36295036 PMCID: PMC9604870 DOI: 10.3390/life12101600] [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: 08/15/2022] [Revised: 09/29/2022] [Accepted: 10/11/2022] [Indexed: 11/05/2022] Open
Abstract
Rhombencephalitis refers to inflammation of the brainstem and cerebellum, and can be caused by infections, autoimmune disorders or paraneoplastic syndromes. The most common infective cause is the bacterium Listeria monocytogenes. Listeria monocytogenes is the predominant species to cause human listeriosis, and is commonly due to the ingestion of contaminated foods. Symptoms include a mild gastroenteritis, fever (often with extreme temperature variations), headache, and myalgia. In more severe cases, invasive disease may lead to bacteraemia and neurolisteriosis. Pregnant women are more susceptible to listeriosis, which is believed to be due to pregnancy-related immune modulation. Maternal-neonatal infection with adverse pregnancy outcomes include neonatal listeriosis, spontaneous miscarriage and intrauterine fetal demise. Diagnosis may be challenging due to initial nonspecific symptoms and low sensitivity and specificity of confirmatory diagnostic laboratory tests. Here, we describe a case of rhombencephalitis in pregnancy, attributed to Listeria, and review the clinical features, diagnosis and multidisciplinary management. Lastly, we describe the immunological response to Listeria monocytogenes and show in vitro pro-inflammatory effects of Listeria monocytogenes on peripheral blood mononuclear cells and placental explants.
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Abstract
PURPOSE OF REVIEW The present article gives an update and outlines the fundamental principles of clinical reasoning and a diagnostic approach to a patient suspected to have acute encephalitis. RECENT FINDINGS Encephalitis remains to be associated with significant mortality and neurological morbidity. Unfortunately, the etiologic diagnosis remains elusive for the majority of the patients with encephalitis preventing targeted therapies. Clinicians could utilize clues such as duration of symptoms, exposure history, cerebrospinal fluid profile, neuroimaging findings and locations, and entertain certain opportunistic infections in immunosuppressed individuals. A comprehensive diagnostic for the most common viral and autoimmune etiologies should be systematically done and prompt empiric antiviral therapy should be started. Evaluation and therapy for autoimmune etiologies should be done for patients with a negative viral work up. Brain biopsy and metagenomic sequencing should be considered for patients with unknown etiologies that are clinically worsening. SUMMARY Encephalitis remains with unacceptable mortality and morbidity with the most common etiologies being idiopathic. A comprehensive diagnostic work up and prompt antiviral and autoimmune therapies are of paramount importance to improve the outcomes of this devastating disease.
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27
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Ball C, Fisicaro R, Morris L, White A, Pacicco T, Raj K, Agarwal A, Lee WC, Yu FF. Brain on fire: an imaging-based review of autoimmune encephalitis. Clin Imaging 2022; 84:1-30. [DOI: 10.1016/j.clinimag.2021.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 11/28/2021] [Accepted: 12/16/2021] [Indexed: 12/28/2022]
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28
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Neuroborreliosis with involvement of rhombencephalon: A case report. IDCases 2022; 28:e01472. [PMID: 35330755 PMCID: PMC8938859 DOI: 10.1016/j.idcr.2022.e01472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/07/2022] [Accepted: 03/07/2022] [Indexed: 11/21/2022] Open
Abstract
We describe a case of a 52 year-old woman who was hospitalized with rhombencephalitis caused by Borrelia burgdorferi sensu lato. The patient presented with intermittent fever, dry cough, fatigue, global headache, night sweats, unintentional weight loss, and neurological symptoms like diplopia, tremor, paresthesia and ataxia. Examination of serum and cerebrospinal fluid (CSF) revealed positive Borrelia burgdorferi-specific antibody index and presence of CSF oligoclonal IgG bands, indicating intrathecal synthesis of Borrelia-specific antibodies. The clinical and biochemical picture thus suggested neuroborreliosis. Unexpectedly a magnetic resonance imaging (MRI) scan demonstrated inflammation in rhombencephalon that are extremely rare in patients with neuroborreliosis. The patient was treated with intravenous ceftriaxone with rapid improvement of her symptoms. The MRI findings were in regress six weeks after onset of antibiotic treatment, and normalized after about seven months.
Rhombencephalitis refers to inflammatory diseases of the rhombencephalon that include the pons, cerebellum and medulla oblongata. Borrelia burgdorferi sensu lato includes the pathogenic genospecies that causes Lyme disease and is transmitted to humans through the bite of infected ticks in the Ixodidae family, in Europe Ixodes ricinus. To diagnose neuroborreliosis can be challenging; it can cause a wide range of unspecific symptoms, the serological tests can be difficult to interpret, the initial CSF findings can be unspecific, and direct test methods like PCR have low sensitivity. Neuroborreliosis should be considered in all patients with neurological symptoms and findings suggesting inflammation in the CNS, also if normal imaging. If the clinical picture suggests neuroborreliosis, initiate treatment as soon as possible, and simultaneously continue to investigate for differential diagnoses if indicated.
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29
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Liao Y, Liu L, Zhou H, Fang F, Liu X. Case Report: Refractory Listeria innocua Meningoencephalitis in a Three-Year-Old Boy. Front Pediatr 2022; 10:857900. [PMID: 35664865 PMCID: PMC9160653 DOI: 10.3389/fped.2022.857900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 04/20/2022] [Indexed: 11/13/2022] Open
Abstract
Listeria innocua is widely distributed in the environment and food and is considered a non-pathogenic bacterium for both humans and animals. To our knowledge, only a few cases of L. innocua infection in humans and ruminants have been reported. Moreover, there has been no report on human L. innocua meningoencephalitis. Here, we report a case of severe refractory meningoencephalitis in a three-year-old boy after infection with L. innocua. The child's first symptoms were a runny nose, high fever, and rashes, which quickly progressed to unconsciousness and convulsions. The initial analysis of cerebral spinal fluid revealed remarkably elevated protein levels and increased white blood cells count. The blood culture of the patient in the early stage was positive for L. innocua. In addition, his brain imaging tests were observed dynamically, and the result showed a speedy progression from multiple intracranial abnormal signals to hydrocephalus and interstitial cerebral edema. After receiving antibiotics and symptomatic treatment for nearly 3 months, the patient's condition improved markedly. However, he still had residual complications such as hydrocephalus. Although L. innocua is considered harmless, it can still cause disease in humans, even severe meningoencephalitis, with rapid progression and poor prognosis. Early discovery, diagnosis, and treatment are necessary to elevate the survival rate and life quality of those patients. Antibiotics should be used with sufficient duration and dosage. Cephalosporins are not suitable for the treatment of L. innocua meningoencephalitis and penicillin antibiotics are preferred for children. The presentation of this case will help to expand our knowledge of Listeria infections and provide a potential candidate for pathogens causing severe childhood central nervous system infection.
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Affiliation(s)
- Yi Liao
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lingling Liu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hua Zhou
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Fang
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinglou Liu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Kolesnik M, Ballout AA, Hameed N, Najjar S. Case Report: HSV-2 Encephalitis Presenting With Chorea; Effects of Infection Alone or Combination of Infection and Autoimmunity? Front Neurol 2021; 12:790514. [PMID: 34956068 PMCID: PMC8709474 DOI: 10.3389/fneur.2021.790514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/12/2021] [Indexed: 11/15/2022] Open
Abstract
Background: Chorea as a symptom of late-onset post-infectious autoimmune encephalitis has been reported with HSV-1 but not HSV-2 encephalitis. Extrapyramidal symptoms are typically associated with the presence of anti-NMDA receptor antibodies but may also exist in antibody-negative individuals. Case: This case highlights a patient who presented with mental status changes and chorea as the initial manifestation of HSV-2 encephalitis. The choreiform movements failed to respond to antiviral medications but were rapidly responsive to plasmapheresis, which, together with abnormal intrathecal immunoglobulin synthesis, suggests a potential contribution of parainfectious immune-mediated process. The patient made a full recovery and a complete resolution of the chorea. Discussion: This is the first case associating HSV-2 encephalitis presentation with chorea. The neurological complications, including chorea, are largely related to active CNS HSV-2 infection, possibly together with triggered CNS autoimmunity despite undetectable CSF neuronal autoantibodies and normal neuroimaging. Early diagnosis and treatment with antiviral agent and immune therapies might be pivotal to optimize the clinical outcome.
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Affiliation(s)
- Michael Kolesnik
- Department of Neurology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, United States
| | - Ahmad A Ballout
- Department of Neurology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, United States
| | - Natasha Hameed
- Department of Neurology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, United States
| | - Souhel Najjar
- Department of Neurology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, United States
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Thakur KT, Miller EH, Glendinning MD, Al-Dalahmah O, Banu MA, Boehme AK, Boubour AL, Bruce SS, Chong AM, Claassen J, Faust PL, Hargus G, Hickman RA, Jambawalikar S, Khandji AG, Kim CY, Klein RS, Lignelli-Dipple A, Lin CC, Liu Y, Miller ML, Moonis G, Nordvig AS, Overdevest JB, Prust ML, Przedborski S, Roth WH, Soung A, Tanji K, Teich AF, Agalliu D, Uhlemann AC, Goldman JE, Canoll P. COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital. Brain 2021; 144:2696-2708. [PMID: 33856027 PMCID: PMC8083258 DOI: 10.1093/brain/awab148] [Citation(s) in RCA: 282] [Impact Index Per Article: 70.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/17/2021] [Accepted: 03/20/2021] [Indexed: 11/14/2022] Open
Abstract
Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.
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Affiliation(s)
- Kiran T Thakur
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Emily Happy Miller
- Department of Medicine, Division of Infectious Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the NewYork Presbyterian Hospital, New York, NY 10032, USA
| | - Michael D Glendinning
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Osama Al-Dalahmah
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Matei A Banu
- Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Amelia K Boehme
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Alexandra L Boubour
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Samuel S Bruce
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Alexander M Chong
- Department of Medicine, Division of Infectious Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the NewYork Presbyterian Hospital, New York, NY 10032, USA
| | - Jan Claassen
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Phyllis L Faust
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Gunnar Hargus
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Richard A Hickman
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Sachin Jambawalikar
- Department of Radiology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Alexander G Khandji
- Department of Radiology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Carla Y Kim
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Robyn S Klein
- Departments of Medicine, Pathology and Immunology, Neurosciences, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Angela Lignelli-Dipple
- Department of Radiology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Chun-Chieh Lin
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA
| | - Yang Liu
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Michael L Miller
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Gul Moonis
- Department of Radiology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Anna S Nordvig
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Jonathan B Overdevest
- Department of Otolaryngology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, The New York Presbyterian Hospital, New York, NY 10032, USA
| | - Morgan L Prust
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Serge Przedborski
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
- Department of Neuroscience, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - William H Roth
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Allison Soung
- Departments of Medicine, Pathology and Immunology, Neurosciences, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Kurenai Tanji
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Andrew F Teich
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Dritan Agalliu
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Anne-Catrin Uhlemann
- Department of Medicine, Division of Infectious Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the NewYork Presbyterian Hospital, New York, NY 10032, USA
| | - James E Goldman
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
| | - Peter Canoll
- Department of Pathology and Cell Biology, Division of Neuropathology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, and the New York Presbyterian Hospital, New York, NY 10032, USA
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32
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Hue CD, Bullrich MB, Lam Shin Cheung VC, Sharma AK, Syed AS, Pandey SK, Morrow SA, Debicki DB. Pearls & Oy-sters: Trigeminal Nerve Dysfunction as the Key Diagnostic Clue to Listeria Rhombencephalitis. Neurology 2021; 97:e1457-e1460. [PMID: 34039730 DOI: 10.1212/wnl.0000000000012273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Christopher Donald Hue
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada.
| | - Maria Bres Bullrich
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
| | - Victor Christopher Lam Shin Cheung
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
| | - Amit Kumar Sharma
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
| | - Asma Saba Syed
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
| | - Sachin Kishore Pandey
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
| | - Sarah Anne Morrow
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
| | - Derek Brian Debicki
- From the Department of Clinical Neurological Sciences (C.D.H., M.B.B., A.K.S., S.A.M., D.B.D.), Department of Medical Imaging (V.C.L.S.C., S.K.P.), and Division of Infectious Diseases, Department of Medicine (A.S.S.), Schulich School of Medicine and Dentistry, Western University; and Lawson Health Research Institute (S.A.M.), London Health Sciences Centre, Canada
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33
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Zhang SY, Harschnitz O, Studer L, Casanova JL. Neuron-intrinsic immunity to viruses in mice and humans. Curr Opin Immunol 2021; 72:309-317. [PMID: 34425410 PMCID: PMC8578315 DOI: 10.1016/j.coi.2021.07.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/08/2021] [Accepted: 07/14/2021] [Indexed: 12/11/2022]
Abstract
Viral encephalitis is a major neglected medical problem. Host defense mechanisms against viral infection of the central nervous system (CNS) have long remained unclear. The few previous studies of CNS-specific immunity to viruses in mice in vivo and humans in vitro have focused on the contributions of circulating leukocytes, resident microglial cells and astrocytes, with neurons long considered passive victims of viral infection requiring protection from extrinsic antiviral mechanisms. The last decade has witnessed the gradual emergence of the notion that neurons also combat viruses through cell-intrinsic mechanisms. Forward genetic approaches in humans have shown that monogenic inborn errors of TLR3, IFN-α/β, or snoRNA31 immunity confer susceptibility to herpes simplex virus 1 (HSV-1) infection of the forebrain, whereas inborn errors of DBR1 underlie brainstem infections due to various viruses, including HSV-1. The study of human pluripotent stem cell (hPSC)-derived CNS-resident cells has unraveled known (i.e. TLR3-dependent IFN-α/β immunity) and new (i.e. snoRNA31-dependent or DBR1-dependent immunity) cell-intrinsic antiviral mechanisms operating in neurons. Reverse genetic approaches in mice have confirmed that some known antiviral mechanisms also operate in mouse neurons (e.g. TLR3 and IFN-α/β immunity). The search for human inborn errors of immunity (IEIs) underlying various forms of viral encephalitis, coupled with mouse models in vivo, and hPSC-based culture models of CNS and peripheral nervous system cells and organoids in vitro, should shed further light on the cell-specific and tissue-specific mechanisms of host defense against viruses in the human brain.
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Affiliation(s)
- Shen-Ying Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France; University of Paris, Imagine Institute, Paris, France.
| | - Oliver Harschnitz
- The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY, USA
| | - Lorenz Studer
- The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY, USA
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France; University of Paris, Imagine Institute, Paris, France; Howard Hughes Medical Institute, New York, NY, USA
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34
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Woo MH, Shin JW. Acute brainstem encephalitis associated with Mycoplasma pneumoniae in an adult: a case report. ENCEPHALITIS 2021; 1:120-123. [PMID: 37470051 PMCID: PMC10295894 DOI: 10.47936/encephalitis.2021.00101] [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: 07/14/2021] [Revised: 09/27/2021] [Accepted: 09/27/2021] [Indexed: 07/21/2023] Open
Abstract
Brainstem encephalitis (BE) associated with Mycoplasma pneumoniae in adults is rare, and the diagnosis is challenging. We describe an uncommon case of BE in an immunocompetent patient. A 43-year-old, otherwise healthy woman visited our emergency department with high fever and a sore throat, and 3 days later she returned with an altered drowsy mental status. Magnetic resonance imaging displayed diffuse swelling in bilateral cerebral regions involving the bilateral pons. The sera tested positive for the immunoglobulin (Ig) M antibody against M. Pneumoniae as detected by an enzyme immunoassay (EIA), and on hospital day 10, the level of IgM index against M. pneumoniae further increased from 1.5 to 2.1. We changed the antibiotic regimen from vancomycin and ceftriaxone to clarithromycin based on detection of M. pneumoniae, and we added intravenous immunoglobulin. After one month, the patient fully recovered from the neurological deficits. A follow-up brain magnetic resonance imaging was performed, which showed completely resolved lesions. Particle agglutination assay (PA) and EIA are both largely used to diagnose M. pneumoniae. Compared to the PA test, the EIA test could be a reliable tool because it separately measures IgM and IgG antibodies. We diagnosed BE associated with M. pneumoniae through EIA with an increasing level of IgM in the acute and subacute paired sera. Early treatment with macrolide antibiotics resulted in a good outcome.
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Affiliation(s)
- Min-Hee Woo
- Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Jung-Won Shin
- Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
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35
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Bastard P, Manry J, Chen J, Rosain J, Seeleuthner Y, AbuZaitun O, Lorenzo L, Khan T, Hasek M, Hernandez N, Bigio B, Zhang P, Lévy R, Shrot S, Reino EJG, Lee YS, Boucherit S, Aubart M, Gijsbers R, Béziat V, Li Z, Pellegrini S, Rozenberg F, Marr N, Meyts I, Boisson B, Cobat A, Bustamante J, Zhang Q, Jouangy E, Abel L, Somech R, Casanova JL, Zhang SY. Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency. J Clin Invest 2021; 131:139980. [PMID: 32960813 DOI: 10.1172/jci139980] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 09/17/2020] [Indexed: 12/16/2022] Open
Abstract
Inborn errors of TLR3-dependent IFN-α/β- and IFN-λ-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-α/β and IFN-λ are unknown. We report a child homozygous for a genomic deletion of the entire coding sequence and part of the 3'-UTR of the last exon of IFNAR1, who died of HSE at the age of 2 years. An older cousin died following vaccination against measles, mumps, and rubella at 12 months of age, and another 17-year-old cousin homozygous for the same variant has had other, less severe, viral illnesses. The encoded IFNAR1 protein is expressed on the cell surface but is truncated and cannot interact with the tyrosine kinase TYK2. The patient's fibroblasts and EBV-B cells did not respond to IFN-α2b or IFN-β, in terms of STAT1, STAT2, and STAT3 phosphorylation or the genome-wide induction of IFN-stimulated genes. The patient's fibroblasts were susceptible to viruses, including HSV-1, even in the presence of exogenous IFN-α2b or IFN-β. HSE is therefore a consequence of inherited complete IFNAR1 deficiency. This viral disease occurred in natural conditions, unlike those previously reported in other patients with IFNAR1 or IFNAR2 deficiency. This experiment of nature indicates that IFN-α/β are essential for anti-HSV-1 immunity in the CNS.
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Affiliation(s)
- Paul Bastard
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Jeremy Manry
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Jie Chen
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Jérémie Rosain
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Yoann Seeleuthner
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | | | - Lazaro Lorenzo
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | | | - Mary Hasek
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Nicholas Hernandez
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Benedetta Bigio
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Peng Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Romain Lévy
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,Pediatric Immunology-Hematology Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France
| | - Shai Shrot
- Department of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eduardo J Garcia Reino
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Yoon-Seung Lee
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Soraya Boucherit
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Mélodie Aubart
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,Department of Pediatric Neurology, Necker Hospital for Sick Children, University of Paris, Paris, France
| | - Rik Gijsbers
- Laboratory of Viral Vector Technology and Gene Therapy and Leuven Viral Vector Core, Faculty of Medicine, KU Leuven, Leuven, Belgium
| | - Vivien Béziat
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France
| | - Zhi Li
- Unit of Cytokine Signaling, Pasteur Institute, INSERM U1221, Paris, France
| | - Sandra Pellegrini
- Unit of Cytokine Signaling, Pasteur Institute, INSERM U1221, Paris, France
| | - Flore Rozenberg
- Laboratory of Virology, University of Paris, AP-HP, Cochin Hospital, Paris, France
| | - Nico Marr
- Research Branch, Sidra Medicine, Doha, Qatar.,College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Isabelle Meyts
- Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.,Department of Pediatrics, Jeffrey Modell Diagnostic and Research Network Center, University Hospitals Leuven, Leuven, Belgium.,Precision Immunology Institute and Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Bertrand Boisson
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Aurélie Cobat
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Jacinta Bustamante
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA.,Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France
| | - Qian Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Emmanuelle Jouangy
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Laurent Abel
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
| | - Raz Somech
- Pediatric Department and Immunology Unit, Edmond and Lily Safra Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel HaShomer, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Jean-Laurent Casanova
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA.,Pediatric Immunology-Hematology Unit, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital for Sick Children, Paris, France.,Howard Hughes Medical Institute, New York, New York, USA
| | - Shen-Ying Zhang
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, New York, USA
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36
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Listeria Rhomboencephalitis in an Immunocompetent Host. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2021. [DOI: 10.1097/ipc.0000000000001024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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37
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Chatterjee A, Saravu K, Mukhopadhyay C, Chandran V. Neurological Melioidosis Presenting as Rhombencephalitis, Optic Neuritis, and Scalp Abscess with Meningitis: A Case Series from Southern India. Neurol India 2021; 69:480-482. [PMID: 33904481 DOI: 10.4103/0028-3886.314590] [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: 11/04/2022]
Abstract
Melioidosis is an under recognized infectious disease which may rarely present with neurological involvement. Neurological melioidosis has protean manifestations, and in this case series we present 3 patients diagnosed from a single center in southern India. The clinical presentation of the patients we describe includes rhomb-encephalitis, scalp infection with subdural and meningeal involvement, and optic neuritis associated with pulmonary melioidosis. We discuss the possible mechanism of involvement of the nervous system, and the recommended treatment. Diagnosis of melioidosis requires a high index of suspicion and should be considered in endemic areas. Through this series we hope to improve the awareness of this infection and its neurological presentation.
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Affiliation(s)
- Aparajita Chatterjee
- Department of Neurology, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
| | - Kavitha Saravu
- Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education (MAHE); Manipal McGill Center for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
| | - Chiranjay Mukhopadhyay
- Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
| | - Vijay Chandran
- Department of Neurology, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
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38
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Double-Negative T-Cell Reaction in a Case of Listeria Meningitis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18126486. [PMID: 34208490 PMCID: PMC8296375 DOI: 10.3390/ijerph18126486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/10/2021] [Accepted: 06/14/2021] [Indexed: 12/30/2022]
Abstract
Gamma delta T-cells are commonly found in response to Listeria monocytogenes infection in mice, whereas this same immunological response has only been reported a few times in vivo in humans. Moreover, gamma delta T-cell response in cerebral spinal fluid samples in conjunction with Listeria meningitis has never been described in medical literature to date. Thus, we describe a 64-year-old male who presented with altered mental status, fever, and neck stiffness. After lumbar puncture revealed elevated glucose, protein, lactate dehydrogenase, and white blood cell count, further cytologic analysis was indicated. The CSF showed a markedly hypercellular sample with a lymphocytic pleocytosis, including some enlarged forms with irregular nuclear contours, and rare macrophage containing intracytoplasmic bacteria. Lymphocyte immunophenotyping was performed via flow cytometric analysis, which ultimately revealed a prominent CD4/CD8 negative T-cell population, suggestive of a gamma delta T-cell population. Thus, an initial suspicion of malignancy was considered but was ruled out due to the absence of mass lesion on imaging and overall features including heterogenous lymphocyte morphology. Shortly after, gram stain and cultures were obtained revealing Listeria monocytogenes. Unfortunately, the patient rapidly succumbed to disease following the diagnosis of Listeria meningitis. Studies suggest that gamma delta T-cells are activated by the protein components of Listeria and thus have been found to be an important mediator of resistance to Listeria infection. Studies have also discovered that the level of activation for these T-cells appears to be tissue specific and dose dependent, with most cases occurring within visceral organs. Hence, we herein present the first case of gamma delta T-cell activation due to Listeria monocytogenes within the cerebral spinal fluid of a human patient.
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Cheema I, Ng N, Chen T. Clinical Reasoning: A 71-Year-Old Man With Horizontal Gaze Palsy, Anarthria, and Quadriparesis. Neurology 2021; 96:1146-1150. [PMID: 33853895 DOI: 10.1212/wnl.0000000000012048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Ikreet Cheema
- From the Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
| | - Nicole Ng
- From the Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Tychicus Chen
- From the Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, Canada
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40
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Infectious ophthalmoplegias. J Neurol Sci 2021; 427:117504. [PMID: 34082150 DOI: 10.1016/j.jns.2021.117504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 05/15/2021] [Accepted: 05/18/2021] [Indexed: 11/21/2022]
Abstract
Though infections account for a significant proportion of patients with ocular motor palsies, there is surprising paucity of literature on infectious ophthalmoplegias. Almost all types of infectious agents (bacteria, viruses, fungi and parasites) can lead to ocular motor palsies. The causative infectious agent can be diagnosed in most cases using an orderly stepwise approach. In this review we discuss how to approach a patient with ophthalmoplegia with main focus on infectious etiologies.
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41
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Paranjape N. Rhombencephalitis due to Listeria monocytogenes. IDCases 2021; 24:e01081. [PMID: 33850723 PMCID: PMC8022819 DOI: 10.1016/j.idcr.2021.e01081] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/18/2021] [Accepted: 03/19/2021] [Indexed: 11/23/2022] Open
Abstract
Brain stem encephalitis is an unusual form of CNS listeriosis that is associated with a high mortality. This is a case of a 46 year-old male with a history of dermatomyositis on methotrexate who presented with fever, headache, assymetrical cranial nerve palsy and right hemiparesis. MRI showed a ring-enhancing lesions in medulla oblongata. CSF cultures grew Listeria monocytogenes. Despite treatment with ampicillin and gentamicin, the patient developed three rare manifestations of neurolisteriosis namely rhombencephalitis, hydrocephalus and brainstem hemorrhage and did not survive. Early detection and treatment is vital in preventing adverse outcomes.
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42
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Raibagkar P, Ramineni A. Autoimmune Neurologic Emergencies. Neurol Clin 2021; 39:589-614. [PMID: 33896534 DOI: 10.1016/j.ncl.2021.01.006] [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] [Indexed: 11/17/2022]
Abstract
Over the past decade, understanding of autoimmune neurologic disorders has exponentially increased. Many patients present as a neurologic emergency and require timely evaluation with rapid management and intensive care. However, the diagnosis is often either missed or delayed, which may lead to a significant burden of disabling morbidity and even mortality. A high level of suspicion in the at-risk population should be maintained to facilitate more rapid diagnosis and prompt treatment. At present, there is no all-encompassing algorithm specifically applicable to the management of fulminant autoimmune neurologic disorders. This article discusses manifestations and management of various autoimmune neurologic emergencies.
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Affiliation(s)
- Pooja Raibagkar
- Concord Hospital Neurology Associates, 246 Pleasant Street, Concord, NH 03301, USA.
| | - Anil Ramineni
- Lahey Hospital & Medical Center, Beth Israel Lahey Health, 41 Mall Road, Burlington, MA 01803, USA
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43
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Huang L, Zhang X, Fang X. Case Report: Epstein-Barr Virus Encephalitis Complicated With Brain Stem Hemorrhage in an Immune-Competent Adult. Front Immunol 2021; 12:618830. [PMID: 33717113 PMCID: PMC7947888 DOI: 10.3389/fimmu.2021.618830] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 01/04/2021] [Indexed: 11/29/2022] Open
Abstract
Encephalitis caused by Epstein-Barr virus infection is uncommon, but most patients have a good outcome after symptomatic treatment. The infiltration of mononuclear cells in blood vessels and necrosis resulting from the immune response to Epstein-Barr virus infection in a very small number of patients seem to be the main cause of death. We describe a fatal case of Epstein-Barr virus encephalitis diagnosed by next-generation sequencing in an immune-competent adult but progressed to brainstem hemorrhage.
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Affiliation(s)
- Lingtong Huang
- Department of Critical Care Units, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Zhang
- Department of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xueling Fang
- Department of Critical Care Units, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Sarma A, Heck JM, Bhatia A, Krishnasarma RS, Pruthi S. Magnetic resonance imaging of the brainstem in children, part 2: acquired pathology of the pediatric brainstem. Pediatr Radiol 2021; 51:189-204. [PMID: 33464360 DOI: 10.1007/s00247-020-04954-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 09/10/2020] [Accepted: 12/20/2020] [Indexed: 10/22/2022]
Abstract
Part 1 of this series of two articles describes conventional and advanced MRI techniques that are useful for evaluating brainstem pathologies. In addition, it provides a review of the embryology, normal progression of myelination, and clinically and radiologically salient imaging anatomy of the normal brainstem. Finally, it discusses congenital diseases of the brainstem with a focus on distinctive imaging features that allow for differentiating pathologies. Part 2 of this series of two articles includes discussion of neoplasms; infections; and vascular, demyelinating, toxic, metabolic and miscellaneous disease processes affecting the brainstem. The ultimate goal of this pair of articles is to empower the radiologist to add clinical value in the care of pediatric patients with brainstem pathologies.
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Affiliation(s)
- Asha Sarma
- Department of Radiology and Radiological Sciences, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN, 37232, USA
| | - Josh M Heck
- Department of Radiology and Radiological Sciences, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN, 37232, USA
| | - Aashim Bhatia
- Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
| | - Rekha S Krishnasarma
- Department of Radiology and Radiological Sciences, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN, 37232, USA
| | - Sumit Pruthi
- Department of Radiology and Radiological Sciences, Monroe Carell Jr. Children's Hospital, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN, 37232, USA.
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45
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Mahdaviani A, Fallahpour M, Seif F, Alyasin S, Abolhassani H, Bousfiha A, Barbouche MR, Olbrich P. Defects in intrinsic and innate immunity. INBORN ERRORS OF IMMUNITY 2021:219-243. [DOI: 10.1016/b978-0-12-821028-4.00002-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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46
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Precht C, Vermathen P, Henke D, Staudacher A, Lauper J, Seuberlich T, Oevermann A, Schweizer-Gorgas D. Correlative Magnetic Resonance Imaging and Histopathology in Small Ruminant Listeria Rhombencephalitis. Front Neurol 2020; 11:518697. [PMID: 33391140 PMCID: PMC7773005 DOI: 10.3389/fneur.2020.518697] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 11/12/2020] [Indexed: 02/05/2023] Open
Abstract
Background: Listeria rhombencephalitis, infection of the brainstem with Listeria monocytogenes, occurs mainly in humans and farmed ruminants and is associated with high fatality rates. Small ruminants (goats and sheep) are a large animal model due to neuropathological similarities. The purpose of this study was to define magnetic resonance imaging (MRI) features of listeria rhombencephalitis in naturally infected small ruminants and correlate them with histopathology. Secondly, the purpose of this study was to compare the results with MRI findings reported in humans. Methods: Twenty small ruminants (13 sheep and 7 goats) with listeria rhombencephalitis were prospectively enrolled and underwent in vivo MRI of the brain, including T2-weighted, fluid attenuation inversion recovery, and T1-weighted sequences pre- and post-contrast administration and postmortem histopathology. In MRI, lesions were characterized by location, extent, border definition, signal intensity, and contrast enhancement. In histopathology, the location, cell type, severity, and chronicity of inflammatory infiltrates and signs of vascular damage were recorded. In addition, histopathologic slides were matched to MRIs, and histopathologic and MRI features were compared. Results: Asymmetric T2-hyperintense lesions in the brainstem were observed in all animals and corresponded to the location and pattern of inflammatory infiltrates in histopathology. Contrast enhancement in the brainstem was observed in 10 animals and was associated with vessel wall damage and perivascular fibrin accumulation in 8 of 10 animals. MRI underestimated the extension into rostral brain parts and the involvement of trigeminal ganglia and meninges. Conclusion: Asymmetric T2-hyperintense lesions in the brainstem with or without contrast enhancement can be established as criteria for the diagnosis of listeria rhombencephalitis in small ruminants. Brainstem lesions were similar to human listeria rhombencephalitis in terms of signal intensity and location. Different from humans, contrast enhancement was a rare finding, and abscessation was not observed.
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Affiliation(s)
- Christina Precht
- Clinical Radiology, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
| | - Peter Vermathen
- Magnetic Resonance Spectroscopy and Methodology, Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Diana Henke
- Division of Neurology, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
| | - Anne Staudacher
- Clinical Radiology, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
| | - Josiane Lauper
- Clinic for Ruminants, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
| | - Torsten Seuberlich
- Neurocenter, Department of Clinical Research and Veterinary Public Health, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
| | - Anna Oevermann
- Neurocenter, Department of Clinical Research and Veterinary Public Health, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
| | - Daniela Schweizer-Gorgas
- Clinical Radiology, Department of Clinical Veterinary Medicine, Vetsuisse-Faculty, University of Bern, Bern, Switzerland
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Abstract
Rhomboencephalitis-inflammation of the brainstem and cerebellum-has myriad clinical presentations including encephalopathy, cranial neuropathies, long tract signs and cerebellar dysfunction and is associated with significant morbidity and mortality. There are a variety of potential underlying causes that respond variably to treatment, including infections, parainfective syndromes, inflammatory disorders including autoimmune encephalitis and paraneoplastic syndromes. Here, we review its clinical presentation and outline a practical approach to its investigation, aiming to facilitate prompt diagnosis and confirmation of the underlying cause, to start appropriate management early and optimise the clinical outcome.
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Affiliation(s)
- Jonathan Cleaver
- Department of Neurology, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
- Department of Neurology, North Bristol NHS Trust, Bristol, UK
| | - Richard James
- Department of Neuroradiology, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
| | - Claire M Rice
- Department of Neurology, North Bristol NHS Trust, Bristol, UK
- Clinical Neuroscience, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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48
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Blum TG, Misch D, Kollmeier J, Thiel S, Bauer TT. Autoimmune disorders and paraneoplastic syndromes in thymoma. J Thorac Dis 2020; 12:7571-7590. [PMID: 33447448 PMCID: PMC7797875 DOI: 10.21037/jtd-2019-thym-10] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Thymomas are counted among the rare tumour entities which are associated with autoimmune disorders (AIDs) and paraneoplastic syndromes (PNS) far more often than other malignancies. Through its complex immunological function in the context of the selection and maturation of T cells, the thymus is at the same time highly susceptible to disruptive factors caused by the development and growth of thymic tumours. These T cells, which are thought to develop to competent immune cells in the thymus, can instead adopt autoreactive behaviour due to the uncontrolled interplay of thymomas and become the trigger for AID or PNS affecting numerous organs and tissues within the human body. While myasthenia gravis is the most prevalent PNS in thymoma, numerous others have been described, be they related to neurological, cardiovascular, gastrointestinal, haematological, dermatological, endocrine or systemic disorders. This review article sheds light on the pathophysiology, epidemiology, specific clinical features and therapeutic options of the various forms as well as courses and outcomes of AID/PNS in association with thymomas. Whenever suitable and backed by the limited available evidence, the perspectives from both the thymoma and the affected organ/tissue will be highlighted. Specific issues addressed are the prognostic significance of thymectomy on myasthenia gravis and other thymoma-associated AID/PND and further the impact and safety of immunotherapies on AID and PND relating to thymomas.
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Affiliation(s)
- Torsten Gerriet Blum
- Department of Pneumology, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
| | - Daniel Misch
- Department of Pneumology, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
| | - Jens Kollmeier
- Department of Pneumology, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
| | - Sebastian Thiel
- Department of Pneumology, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
| | - Torsten T Bauer
- Department of Pneumology, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
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49
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Unusual cause at an unusual time-Powassan virus rhombencephalitis. Int J Infect Dis 2020; 103:88-90. [PMID: 33227515 DOI: 10.1016/j.ijid.2020.11.159] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 11/10/2020] [Accepted: 11/12/2020] [Indexed: 11/20/2022] Open
Abstract
Powassan virus lineage II (POWV) is an emerging tick-borne neurotropic pathogen, transmitted to humans by the bite of infected Ixodes scapularis ticks. In the United States, the disease is most prevalent in the Northeast and the upper Midwest and occurs mostly during the spring and summer months when tick activity is the highest. Some patients infected with POWV develop severe encephalitis, with high mortality. We report the case of a 42-year-old healthy man who developed progressive diplopia and dysarthria in December following a deer hunting trip. Routine blood work was unrevealing and MRI was normal. Extensive work-up for infectious, autoimmune, and paraneoplastic causes was positive only for POWV. The patient was treated with supportive care and intravenous corticosteroids, with an excellent outcome. We present a rare clinical presentation of a potentially fatal emerging disease that responded favorably to corticosteroids.
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50
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Madhavan AA, Carr CM, Morris PP, Flanagan EP, Kotsenas AL, Hunt CH, Eckel LJ, Lindell EP, Diehn FE. Imaging Review of Paraneoplastic Neurologic Syndromes. AJNR Am J Neuroradiol 2020; 41:2176-2187. [PMID: 33093137 DOI: 10.3174/ajnr.a6815] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 06/29/2020] [Indexed: 12/19/2022]
Abstract
Paraneoplastic syndromes are systemic reactions to neoplasms mediated by immunologic or hormonal mechanisms. The most well-recognized paraneoplastic neurologic syndrome, both clinically and on imaging, is limbic encephalitis. However, numerous additional clinically described syndromes affect the brain, spinal cord, and peripheral nerves. Many of these syndromes can have imaging findings that, though less well described, are important in making the correct diagnosis. Moreover, imaging in these syndromes frequently mimics more common pathology, which can be a diagnostic challenge for radiologists. Our goal is to review the imaging findings of paraneoplastic neurologic syndromes, including less well-known entities and atypical presentations of common entities. Specifically, we discuss limbic encephalitis, paraneoplastic cerebellar degeneration, paraneoplastic brain stem encephalitis, cranial neuropathy, myelitis, and polyneuropathy. We also demonstrate common diagnostic pitfalls that can be encountered when imaging these patients.
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Affiliation(s)
- A A Madhavan
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - C M Carr
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - P P Morris
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - E P Flanagan
- Department of Neurology (E.P.F.), Mayo Clinic, Rochester, Minnesota
| | - A L Kotsenas
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - C H Hunt
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - L J Eckel
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - E P Lindell
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
| | - F E Diehn
- From the Division of Neuroradiology, Department of Radiology (A.A.M., C.M.C., P.P.M., A.L.K., C.H.H., L.J.E., E.P.L., F.E.D.)
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