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1.
Viruses ; 16(5)2024 04 30.
Article in English | MEDLINE | ID: mdl-38793601

ABSTRACT

West Nile virus (WNV) is an arbovirus spread primarily by Culex mosquitoes, with humans being a dead-end host. WNV was introduced to Florida in 2001, with 467 confirmed cases since. It is estimated that 80 percent of cases are asymptomatic, with mild cases presenting as a non-specific flu-like illness. Currently, detection of WNV in humans occurs primarily in healthcare settings via RT-PCR or CSF IgM when patients present with severe manifestations of disease including fever, meningitis, encephalitis, or acute flaccid paralysis. Given the short window of detectable viremia and requirement for CSF sampling, most WNV infections never receive an official diagnosis. This study utilized enzyme-linked immunosorbent assay (ELISA) to detect WNV IgG antibodies in 250 patient serum and plasma samples collected at Tampa General Hospital during 2020 and 2021. Plaque reduction neutralization tests were used to confirm ELISA results. Out of the 250 patients included in this study, 18.8% of them were IgG positive, consistent with previous WNV exposure. There was no relationship between WNV exposure and age or sex.


Subject(s)
Antibodies, Viral , Immunoglobulin G , West Nile Fever , West Nile virus , Humans , West Nile virus/immunology , West Nile Fever/epidemiology , West Nile Fever/virology , Florida/epidemiology , Male , Female , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Middle Aged , Seroepidemiologic Studies , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Adult , Aged , Young Adult , Adolescent , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay , Hospitalization , Immunoglobulin M/blood , Immunoglobulin M/cerebrospinal fluid
2.
Eur J Paediatr Neurol ; 50: 51-56, 2024 May.
Article in English | MEDLINE | ID: mdl-38636242

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. An intrathecal IgM synthesis is associated with a more rapid progression of MS and the intrathecal immune response to measles -, rubella -and varicella zoster virus (MRZR) which, if present, increases the likelihood of a diagnosis of MS in adults. OBJECTIVE: To evaluate the frequency of an intrathecal IgM synthesis and MRZR in children with MS. MethodsChildren with MS and a data set including clinical and treatment history, MRI at onset, in addition to a CSF analysis, and determination of antibody index (AI) of measles, rubella, and zoster antibodies, were eligible. The presence of an intrathecal IgM synthesis and/or a positive MRZ reaction were compared to biomarkers of a more progressive disease course. RESULTS: In 75 children with MS, OCBs were present in 93.3 %). 49,2 % experienced their first relapse within 6 months. 50.7 % had a total lesion load of more than 10 lesions in the first brain MRI. Spinal lesions were identified in 64 %. 23.5 % had a positive MRZR and 40.3 % an intrathecal IgM synthesis. No significant associations were detected between the presence of an intrathecal IgM synthesis and MRZR and parameters including the relapse rate in the first two years. CONCLUSION: An intrathecal IgM synthesis and a positive MRZR are found in a subset of MS children but are not associated with markers associated with a poor prognosis.


Subject(s)
Immunoglobulin M , Magnetic Resonance Imaging , Multiple Sclerosis , Humans , Male , Immunoglobulin M/cerebrospinal fluid , Child , Female , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/immunology , Multiple Sclerosis/cerebrospinal fluid , Adolescent , Herpesvirus 3, Human/immunology , Antibodies, Viral/cerebrospinal fluid , Antibodies, Viral/blood , Child, Preschool , Measles virus/immunology , Rubella virus/immunology , Disease Progression , Brain/diagnostic imaging , Biomarkers/cerebrospinal fluid
3.
Eur J Clin Microbiol Infect Dis ; 43(6): 1139-1148, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38613705

ABSTRACT

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.


Subject(s)
Antibodies, Viral , Chickenpox , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Luminescent Measurements , Measles virus , Measles , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Measles/diagnosis , Measles/immunology , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Luminescent Measurements/methods , Enzyme-Linked Immunosorbent Assay/methods , Child , Male , Female , Adult , Adolescent , Chickenpox/diagnosis , Chickenpox/immunology , Measles virus/immunology , Child, Preschool , Young Adult , Middle Aged , Herpesvirus 3, Human/immunology , Sensitivity and Specificity , Infant , Aged , Immunoassay/methods , Reagent Kits, Diagnostic/standards
4.
Ann Neurol ; 95(6): 1112-1126, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38551149

ABSTRACT

OBJECTIVE: Specific human leucocyte antigen (HLA) alleles are not only associated with higher risk to develop multiple sclerosis (MS) and other autoimmune diseases, but also with the severity of various viral and bacterial infections. Here, we analyzed the most specific biomarker for MS, that is, the polyspecific intrathecal IgG antibody production against measles, rubella, and varicella zoster virus (MRZ reaction), for possible HLA associations in MS. METHODS: We assessed MRZ reaction from 184 Swiss patients with MS and clinically isolated syndrome (CIS) and 89 Swiss non-MS/non-CIS control patients, and performed HLA sequence-based typing, to check for associations of positive MRZ reaction with the most prevalent HLA alleles. We used a cohort of 176 Swedish MS/CIS patients to replicate significant findings. RESULTS: Whereas positive MRZ reaction showed a prevalence of 38.0% in MS/CIS patients, it was highly specific (97.7%) for MS/CIS. We identified HLA-DRB1*15:01 and other tightly linked alleles of the HLA-DR15 haplotype as the strongest HLA-encoded risk factors for a positive MRZ reaction in Swiss MS/CIS (odds ratio [OR], 3.90, 95% confidence interval [CI] 2.05-7.46, padjusted = 0.0004) and replicated these findings in Swedish MS/CIS patients (OR 2.18, 95%-CI 1.16-4.02, padjusted = 0.028). In addition, female MS/CIS patients had a significantly higher probability for a positive MRZ reaction than male patients in both cohorts combined (padjusted <0.005). INTERPRETATION: HLA-DRB1*15:01, the strongest genetic risk factor for MS, and female sex, 1 of the most prominent demographic risk factors for developing MS, predispose in MS/CIS patients for a positive MRZ reaction, the most specific CSF biomarker for MS. ANN NEUROL 2024;95:1112-1126.


Subject(s)
Immunoglobulin G , Multiple Sclerosis , Humans , Female , Male , Multiple Sclerosis/genetics , Multiple Sclerosis/immunology , Multiple Sclerosis/cerebrospinal fluid , Immunoglobulin G/blood , Adult , Middle Aged , Herpesvirus 3, Human/immunology , Herpesvirus 3, Human/genetics , HLA-DRB1 Chains/genetics , Sweden/epidemiology , Cohort Studies , Young Adult , Rubella virus/genetics , Rubella virus/immunology , HLA Antigens/genetics , Antibodies, Viral/cerebrospinal fluid , Antibodies, Viral/blood , Alleles , Switzerland/epidemiology
5.
Article in Chinese | MEDLINE | ID: mdl-38403427

ABSTRACT

Forest encephalitis is a natural focal disease transmitted through the bite of hard ticks, and its pathogen is the tick-borne encephalitis virus from the Flaviviridae family. The mortality rate of forest encephalitis is relatively high, making laboratory testing significant in diagnosing this disease. This article elaborates on the etiological diagnostic methods and recent research progress in forest encephalitis. Laboratory tests for forest encephalitis mainly include routine examinations, serological tests, virus isolation, and molecular biological testing. The detection of serum-specific IgM antibodies against the forest encephalitis virus is of great importance for early diagnosis, and specific IgG antibodies serve as a "gold standard" for differentiation from other diseases. Techniques such as enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence assay for detecting specific IgM antibodies in serum and/or cerebrospinal fluid, the serum hemagglutination inhibition test or serum complement fixation test, and the double serum hemagglutination inhibition test or complement fixation test all contribute to the early diagnosis. The development of molecular testing methods is rapid, and techniques such as metabolomics, digital PCR, and matrix metalloproteinases are also applied in the early diagnosis of forest encephalitis.


Subject(s)
Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Humans , Encephalitis, Tick-Borne/diagnosis , Antibodies, Viral/cerebrospinal fluid , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin M/cerebrospinal fluid
6.
Indian J Pediatr ; 90(10): 1038-1040, 2023 10.
Article in English | MEDLINE | ID: mdl-36765003

ABSTRACT

The study compared the clinical profile and outcomes of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) in children. Fifty-six consecutive children with symptoms fulfilling the WHO clinical case definition of AES from June 2018 to June 2020 were included in the study. All patients who tested positive for either serum or cerebrospinal fluid (CSF) anti-JE-IgM antibodies were JE patients (n = 24) and compared with non-JE AES cases (n = 32). Fever, seizures, and altered sensorium were the most common presenting symptoms. Low GCS, status epilepticus, meningeal irritation, raised CSF protein, and INR > 1.5 of JE children showed significant association with mortality (p value < 0.05), whereas only low GCS showed significant association in non-JE AES cases. The JE-specific mortality rate was 29%, which was less than the mortality rate of non-JE AES children at 41%. Both JE and non-JE AES children had a similar clinical profile, but only the JE children's poor clinical and laboratory parameters were associated with adverse outcomes.


Subject(s)
Acute Febrile Encephalopathy , Encephalitis, Japanese , Status Epilepticus , Child , Humans , Encephalitis, Japanese/diagnosis , Encephalitis, Japanese/epidemiology , Acute Febrile Encephalopathy/epidemiology , Seizures , Fever , Antibodies, Viral/cerebrospinal fluid
7.
Fluids Barriers CNS ; 19(1): 61, 2022 Jul 29.
Article in English | MEDLINE | ID: mdl-35906648

ABSTRACT

INTRODUCTION: Infectious and immunological theories of schizophrenia have been discussed for over a century. Contradictory results for infectious agents in association with schizophrenia spectrum disorders (SSDs) were reported. The rationale of this study was to investigate intrathecal antibody synthesis of the most frequently discussed neurotropic pathogens using a pathogen-specific antibody index (AI) in patients with SSD in comparison to controls. METHODS: In 100 patients with SSD and 39 mentally healthy controls with idiopathic intracranial hypertension (IIH), antibodies against the herpesviruses EBV, CMV, and HSV 1/2 as well as the protozoan Toxoplasma gondii, were measured in paired cerebrospinal fluid (CSF) and serum samples with ELISA-kits. From these antibody concentrations the pathogen-specific AIs were determined with the assumption of intrathecal antibody synthesis at values > 1.5. RESULTS: No significant difference was detected in the number of SSD patients with elevated pathogen-specific AI compared to the control group. In a subgroup analysis, a significantly higher EBV AI was observed in the group of patients with chronic SSD compared to patients with first-time SSD diagnosis (p = 0.003). In addition, two identified outlier EBV patients showed evidence for polyspecific immune reactions (with more than one increased AI). CONCLUSIONS: Evidence for the role of intrathecal EBV antibody synthesis was found in patients with chronic SSD compared to those first diagnosed. Apart from a possible infectious factor in SSD pathophysiology, the evidence for polyspecific immune response in outlier patients may also suggest the involvement of further immunological processes in a small subgroup of SSD patients.


Subject(s)
Schizophrenia , Antibodies, Viral/cerebrospinal fluid , Enzyme-Linked Immunosorbent Assay/methods , Humans
8.
Int J Mol Sci ; 22(19)2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34638953

ABSTRACT

Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system-most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.


Subject(s)
Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne/blood , Encephalitis, Tick-Borne/cerebrospinal fluid , Animals , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Blood-Brain Barrier/pathology , Chemokines/blood , Chemokines/cerebrospinal fluid , Encephalitis, Tick-Borne/diagnosis , Encephalitis, Tick-Borne/genetics , Encephalitis, Tick-Borne/virology , Genetic Predisposition to Disease , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/blood , Immunoglobulin M/cerebrospinal fluid , Immunoglobulin lambda-Chains/blood , Immunoglobulin lambda-Chains/cerebrospinal fluid , Matrix Metalloproteinase 9/blood , Matrix Metalloproteinase 9/cerebrospinal fluid
9.
JAMA Neurol ; 78(12): 1503-1509, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34694339

ABSTRACT

Importance: Neuropsychiatric manifestations of COVID-19 have been reported in the pediatric population. Objective: To determine whether anti-SARS-CoV-2 and autoreactive antibodies are present in the cerebrospinal fluid (CSF) of pediatric patients with COVID-19 and subacute neuropsychiatric dysfunction. Design, Setting, and Participants: This case series includes 3 patients with recent SARS-CoV-2 infection as confirmed by reverse transcriptase-polymerase chain reaction or IgG serology with recent exposure history who were hospitalized at the University of California, San Francisco Benioff Children's Hospital and for whom a neurology consultation was requested over a 5-month period in 2020. During this period, 18 total children were hospitalized and tested positive for acute SARS-CoV-2 infection by reverse transcriptase-polymerase chain reaction or rapid antigen test. Main Outcomes and Measures: Detection and characterization of CSF anti-SARS-CoV-2 IgG and antineural antibodies. Results: Of 3 included teenaged patients, 2 patients had intrathecal anti-SARS-CoV-2 antibodies. CSF IgG from these 2 patients also indicated antineural autoantibodies on anatomic immunostaining. Autoantibodies targeting transcription factor 4 (TCF4) in 1 patient who appeared to have a robust response to immunotherapy were also validated. Conclusions and Relevance: Pediatric patients with COVID-19 and prominent subacute neuropsychiatric symptoms, ranging from severe anxiety to delusional psychosis, may have anti-SARS-CoV-2 and antineural antibodies in their CSF and may respond to immunotherapy.


Subject(s)
Antibodies, Viral/cerebrospinal fluid , Autoantibodies/cerebrospinal fluid , COVID-19/complications , COVID-19/immunology , Mental Disorders/cerebrospinal fluid , Mental Disorders/etiology , Nervous System Diseases/cerebrospinal fluid , Nervous System Diseases/etiology , Adolescent , Animals , Anxiety/etiology , Anxiety/psychology , Autoimmunity , Female , Humans , Male , Marijuana Smoking/immunology , Mice , Movement Disorders/etiology , Neurologic Examination , Transcription Factor 4/immunology
10.
Article in English | MEDLINE | ID: mdl-34429365

ABSTRACT

BACKGROUND AND OBJECTIVES: Neurotropic viruses are suspected to play a role in the pathogenesis of autoimmune diseases of the CNS such as the association between the Epstein-Barr virus (EBV) and multiple sclerosis (MS). A group of autoimmune encephalitis (AE) is linked to antibodies against neuronal cell surface proteins. Because CNS infection with the herpes simplex virus can trigger anti-NMDA receptor (NMDAR) encephalitis, a similar mechanism for EBV and other neurotropic viruses could be postulated. To investigate for previous viral infections of the CNS, intrathecally produced virus-specific antibody synthesis was determined in patients with AE. METHODS: Antibody-specific indices (AIs) against EBV and measles, rubella, varicella zoster, herpes simplex virus, and cytomegalovirus were determined in 27 patients having AE (anti-NMDAR encephalitis, n = 21, and LGI1 encephalitis, n = 6) and in 2 control groups comprising of 30 patients with MS and 21 patients with noninflammatory CNS diseases (NIND), which were sex and age matched. RESULTS: An intrathecal synthesis of antibodies against EBV was found in 5/27 (19%) patients with AE and 2/30 (7%) of the patients with MS. All these patients had also at least 1 additional elevated virus-specific AI. In contrast, in none of the patients with NIND, an elevated virus-specific AI was detected. DISCUSSION: Intrathecally produced antibodies against EBV can be found in patients with AE and MS but only together with antibodies against different neurotropic viruses. Evidence of these antibodies is the result of a polyspecific immune response similar yet distinct from MS response rather than an elapsed infection of the CNS.


Subject(s)
Antibodies, Viral/cerebrospinal fluid , Autoimmune Diseases of the Nervous System/cerebrospinal fluid , Encephalitis, Viral/cerebrospinal fluid , Herpesvirus 4, Human/immunology , Simplexvirus/immunology , Adolescent , Adult , Aged , Antibodies, Viral/blood , Autoimmune Diseases of the Nervous System/blood , Encephalitis, Viral/blood , Female , Humans , Male , Middle Aged , Young Adult
11.
Article in English | MEDLINE | ID: mdl-34135107

ABSTRACT

OBJECTIVE: Coronavirus disease (COVID-19) has been associated with a large variety of neurologic disorders. However, the mechanisms underlying these neurologic complications remain elusive. In this study, we aimed at determining whether neurologic symptoms were caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) direct infection or by either systemic or local proinflammatory mediators. METHODS: In this cross-sectional study, we checked for SARS-CoV-2 RNA by quantitative reverse transcription PCR, SARS-CoV-2-specific antibodies, and 49 cytokines/chemokines/growth factors (by Luminex) in the CSF +/- sera of a cohort of 22 COVID-19 patients with neurologic presentation and 55 neurologic control patients (inflammatory neurologic disorder [IND], noninflammatory neurologic disorder, and MS). RESULTS: We detected anti-SARS-CoV-2 immunoglobulin G in patients with severe COVID-19 with signs of intrathecal synthesis for some of them. Of the 4 categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines, and growth factors. By contrast, patients with COVID-19 did not present overall upregulation of inflammatory mediators in the CSF. However, patients with severe COVID-19 (intensive care unit patients) exhibited higher concentrations of CCL2, CXCL8, and vascular endothelium growth factor A (VEGF-A) in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated albumin ratio and correlated with the increase of peripheral inflammation (serum hepatocyte growth factor [HGF] and CXCL10). CONCLUSIONS: Our results do not indicate active replication of SARS-CoV-2 in the CSF or signs of massive inflammation in the CSF compartment but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.


Subject(s)
Brain Diseases/etiology , COVID-19/complications , Cytokines/cerebrospinal fluid , Inflammation/etiology , Neurovascular Coupling , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , Antibodies, Viral/cerebrospinal fluid , Brain Diseases/cerebrospinal fluid , Brain Diseases/immunology , Brain Diseases/physiopathology , COVID-19/cerebrospinal fluid , COVID-19/immunology , Critical Care , Cross-Sectional Studies , Cytokines/blood , Electroencephalography , Female , Humans , Immunoglobulin G/cerebrospinal fluid , Inflammation/cerebrospinal fluid , Inflammation/immunology , Interleukin-8/cerebrospinal fluid , Male , Middle Aged , Neurovascular Coupling/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Young Adult
12.
J Med Virol ; 93(7): 4247-4257, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33724490

ABSTRACT

To provide instructive clues for clinical practice and further research of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we analyzed the existing literature on viral neuroinvasion of SARS-CoV-2 in coronavirus disease 2019 (COVID-19) patients. To date, SARS-CoV-2 has been detected in the cerebrospinal fluid (CSF) or brain parenchyma in quite a few patients, which provide undeniable evidence for the neuroinvasive potential of this novel coronavirus. In contrast with the cerebrum and cerebellum, the detection rate of SARS-CoV-2 was higher in the olfactory system and the brainstem, both of which also showed severe microgliosis and lymphocytic infiltrations. As compared with the number of patients who underwent viral testing in the central nervous system (CNS), the number of patients showing positive results seems very small. However, it seems too early to conclude that the neuroinvasion of SARS-CoV-2 is rare in COVID-19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. Moreover, the primary symptoms and/or causes of death were distinctly different among examined patients, which probably caused more conspicuous pathological changes than those due to the direct infection that usually localized to specific brain areas. Unfortunately, most autopsy studies did not provide sufficient details about neurological symptoms or suspected diagnoses of the examined patients, and the documentation of neuropathological changes was often incomplete. Given the complex pathophysiology of COVID-19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.


Subject(s)
Brain/pathology , COVID-19/pathology , Cerebrospinal Fluid/virology , Olfactory Bulb/virology , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Brain/virology , Humans , Nervous System Diseases/virology , Olfactory Mucosa/virology , SARS-CoV-2/isolation & purification
13.
Stroke ; 51(12): 3719-3722, 2020 12.
Article in English | MEDLINE | ID: mdl-33054673

ABSTRACT

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.


Subject(s)
COVID-19/diagnostic imaging , Cerebral Arteries/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Cerebrovascular Disorders/diagnostic imaging , Ischemic Stroke/diagnostic imaging , Aged , Antibodies, Viral/cerebrospinal fluid , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , COVID-19/cerebrospinal fluid , COVID-19/complications , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Cerebral Hemorrhage/etiology , Cerebrospinal Fluid/immunology , Cerebrospinal Fluid/virology , Cerebrovascular Disorders/cerebrospinal fluid , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/physiopathology , Consciousness Disorders/etiology , Consciousness Disorders/physiopathology , Contrast Media , Critical Illness , Electroencephalography , Female , Humans , Ischemic Stroke/etiology , Magnetic Resonance Imaging , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index , Switzerland , Tertiary Care Centers , Tomography, X-Ray Computed
14.
Front Immunol ; 11: 2142, 2020.
Article in English | MEDLINE | ID: mdl-33072077

ABSTRACT

Human herpesvirus-6A (HHV-6A) and -6B (HHV-6B) might be involved in the etiopathogenesis of multiple sclerosis (MS), especially the HHV-6A. We aim at assessing, for the first time in the scientific literature, the HHV-6A/B microRNAs in MS patients. We analyzed the miRNAs of HHV-6A: miR-U86, and -6B: hhv6b-miR-Ro6-1, -2, -3-3p, -3-5p, and -4 in paired samples of serum and CSF of 42 untreated MS patients and 23 patients with other neurological diseases (OND), using Taqman MicroRNA Assays. Intrathecal HHV-6A/B antibody production and anti-HHV-6A/B IgG/IgM levels in serum were measured. MS clinical data were available. We detected the following miRNAs: hhv6b-miR-Ro6-2 (serum: MS:97.7%, OND:95.7%; CSF: MS:81%, OND:86.4%), 3-3p (serum: MS:4.8%, OND:0%; CSF: MS:2.4%, OND:4.5%), -3-5p (serum: MS:95.2%, OND:91.3%; CSF: MS:50%, OND:54.5%), and miR-U86 (serum: MS:54.8%, OND:47.8%; CSF: MS:11.9%, OND:9.1%). In the serum of the whole population (MS and OND patients) we found a significant correlation between the levels of hhv6b-miR-Ro6-2 and -3-5p (Spearman r = 0.839, pcorr = 3E-13), -2 and miR-U86 (Spearman r = 0.578, pcorr = 0.001) and -3-5p and miR-U86 (Spearman r = 0.698, pcorr = 1.34E-5); also in the CSF, between hhv6b-miR-Ro6-2 and -3-5p (Spearman r = 0.626, pcorr = 8.52E-4). These correlations remained statistically significant when both populations were considered separately. The anti-HHV-6A/B IgG levels in CSF and the intrathecal antibody production in positive MS patients for hhv6b-miR-Ro6-3-5p were statistically significant higher than in the negative ones (pcorr = 0.006 and pcorr = 0.036). The prevalence of miR-U86 (30.8%) in the CSF of individuals without gadolinium-enhancing lesions was higher (p = 0.035) than in the ones with these lesions (0%); however, the difference did not withstand Bonferroni correction (pcorr = 0.105). We propose a role of HHV-6A/B miRNAs in the maintenance of the viral latency state. Further investigations are warranted to validate these results and clarify the function of these viral miRNAs.


Subject(s)
Herpesvirus 6, Human/isolation & purification , MicroRNAs/blood , MicroRNAs/cerebrospinal fluid , Multiple Sclerosis/virology , RNA, Viral/blood , Adult , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Case-Control Studies , Female , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/blood , Immunoglobulin M/cerebrospinal fluid , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnostic imaging , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , RNA, Viral/cerebrospinal fluid , Retrospective Studies , Virus Latency/genetics
15.
J Affect Disord ; 277: 337-340, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32858315

ABSTRACT

BACKGROUND: In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms. CASE REPORT: Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS). LIMITATION: This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool. CONCLUSION: This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.


Subject(s)
Bipolar Disorder/etiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Antibodies, Viral/cerebrospinal fluid , Antipsychotic Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , Bipolar Disorder/cerebrospinal fluid , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Brain/diagnostic imaging , COVID-19 , COVID-19 Testing , Chest Pain , China , Clinical Laboratory Techniques , Cobicistat/therapeutic use , Coronavirus Infections/cerebrospinal fluid , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Darunavir/therapeutic use , Dyspnea , Fever , Glucocorticoids/therapeutic use , Humans , Indoles/therapeutic use , Magnetic Resonance Imaging , Male , Methylprednisolone/therapeutic use , Middle Aged , Moxifloxacin/therapeutic use , Olanzapine/therapeutic use , Pandemics , Pharyngitis , Pneumonia, Viral/cerebrospinal fluid , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
16.
Paediatr Int Child Health ; 40(4): 255-260, 2020 11.
Article in English | MEDLINE | ID: mdl-32744918

ABSTRACT

A 4-year-old boy was admitted with an acute onset fever for 4 days and drowsiness for 3 days, followed by progressive flaccid weakness of both lower limbs and encephalopathy soon after admission. He had sustained a WHO Class III stray dog bite 2 weeks previously and had received three doses of post-exposure rabies vaccination with purified vero cell vaccine but not rabies immunoglobulin. He was diagnosed with rabies based on the presence of rabies virus neutralising antibody in CSF (Day 1 1:128 and Day 26 1:2048) and typical findings on neuro-imaging. Rabies viral RNA was not detected in CSF, in saliva or on nuchal skin. The child survived with supportive treatment alone but he has extensive neurological sequelae. This report demonstrates the detailed clinico-investigative profile of a child who survived rabies following inadequate post-exposure prophylaxis and adds to the sparse knowledge of this usually fatal condition. ABBREVIATIONS: ADEM, acute disseminated encephalomyelitis; CBNAAT, cartridge-based nucleic acid amplification test; CSF, cerebrospinal fluid; EEG, electroencephalogram; GCS, Glasgow coma scale; EVM, eye opening, best verbal response, best motor response; IM, intramuscular; IVIg, intravenous immunoglobulin; MRC, Medical Research Council; MRI/FLAIR, magnetic resonance imaging/fluid attenuation inversion recovery; PCR, polymerase chain reaction; RFFIT, rapid fluorescent focus inhibition test; RIg, rabies immunoglobulin; RNA, ribonucleic acid; WBC, white blood cells; WHO, World Health Organization.


Subject(s)
Rabies/therapy , Antibodies, Viral/cerebrospinal fluid , Child, Preschool , Humans , Magnetic Resonance Imaging , Male , RNA, Viral/analysis , Survivors
19.
J Neurovirol ; 26(4): 556-564, 2020 08.
Article in English | MEDLINE | ID: mdl-32572833

ABSTRACT

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine.


Subject(s)
Basal Ganglia/pathology , Cerebrum/pathology , DNA, Viral/genetics , Encephalitis, Viral/pathology , Herpesvirus 1, Suid/genetics , Meat/virology , Pseudorabies/pathology , Adult , Animals , Antibodies, Viral/cerebrospinal fluid , Basal Ganglia/diagnostic imaging , Basal Ganglia/virology , Cerebrum/diagnostic imaging , Cerebrum/virology , China , DNA, Viral/cerebrospinal fluid , Encephalitis, Viral/cerebrospinal fluid , Encephalitis, Viral/diagnosis , Encephalitis, Viral/virology , Female , Herpesvirus 1, Suid/growth & development , Herpesvirus 1, Suid/pathogenicity , High-Throughput Nucleotide Sequencing , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Polymerase Chain Reaction , Pseudorabies/cerebrospinal fluid , Pseudorabies/diagnosis , Pseudorabies/virology , Swine
20.
Jpn J Infect Dis ; 73(5): 381-382, 2020 Sep 24.
Article in English | MEDLINE | ID: mdl-32350214

ABSTRACT

Japanese encephalitis (JE) is a clinical disease caused by inflammation of the central nervous system. The symptoms of this disease range broadly in severity from mild febrile illness to acute meningomyeloencephalitis. JE has been associated with a variety of neurological abnormalities, such as altered sensorium, seizures, focal neurological deficit, and acute flaccid paralysis (AFP). However, to date, AFP has never been reported as an initial manifestation of JE. Here, we present a case of AFP manifesting as the initial symptom of JE in a Chinese patient. A 30-year-old Chinese man was admitted to the West China Hospital of Sichuan University after experiencing AFP in the right upper limb, followed by hyperpyrexia and unconsciousness. Assay of cerebrospinal fluid from a lumbar puncture revealed high levels of proteins and anti- JE virus IgM antibodies. Intravenous acyclovir was administered; however, the weakness persisted and more extensive muscle wasting from the proximal to distal right upper limb occurred over 7 months. This case report highlights that JE needs to be added to the differential diagnosis of AFP in adults, especially in JE endemic seasons and areas.


Subject(s)
Central Nervous System Viral Diseases/diagnosis , Central Nervous System Viral Diseases/etiology , Encephalitis, Japanese/complications , Encephalitis, Japanese/diagnosis , Myelitis/diagnosis , Myelitis/etiology , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/etiology , Acyclovir/therapeutic use , Administration, Intravenous , Adult , Antibodies, Viral/cerebrospinal fluid , Antiviral Agents/therapeutic use , China , Encephalitis Virus, Japanese/immunology , Encephalitis Virus, Japanese/isolation & purification , Encephalitis, Japanese/drug therapy , Humans , Immunoglobulin M/cerebrospinal fluid , Male , Treatment Outcome
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