ABSTRACT
OBJECTIVE: To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES). METHODS: A retrospective audit was conducted between January 2017 to July 2022. We included children aged < 18 years with a diagnosis of AES for whom a CSF analysis study including FAME panel testing performed within 48 hours of admission was available. Electronic medical records were reviewed for details including demographic profile, clinical presentation, investigations and outcome. RESULTS: Out of 157 CSF samples sent for FAME panel testing, 49 were positive (31.4%.) Viral pathogens were identified in 42 (Enterovirus: 31, Human herpes virus 6: 9, Varicella zoster virus: 1, and Cytomegalovirus: 1) Bacterial pathogens were identified in 6 (Streptococcus pneumoniae: 2, Streptococcus agalactiae: 2, Hemophilus influenzae: 1, and Escherischia coli: 1). Fungal etiology (Cryptococcus neoformans) was detected in one child. Antibiotics could be stopped within 72 hours of initiation in 42 children in whom a viral etiology was established. Acyclovir could be stopped in 21 out of 32 children within 72 hours after the FAME panel testing. FAME panel was presumed to be false positive in 4 children. CONCLUSION: Etiology of AES could be established in nearly a third of children with AES using the rapid diagnostic FAME panel testing in CSF and it was found to be effective in reducing empirical antibiotic/antiviral therapy.
Subject(s)
Acute Febrile Encephalopathy , Humans , India/epidemiology , Retrospective Studies , Child , Child, Preschool , Female , Male , Infant , Acute Febrile Encephalopathy/diagnosis , Acute Febrile Encephalopathy/drug therapy , Acute Febrile Encephalopathy/epidemiology , Adolescent , Meningoencephalitis/drug therapy , Meningoencephalitis/diagnosis , Meningoencephalitis/cerebrospinal fluidABSTRACT
Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.
Subject(s)
Autoimmune Diseases of the Nervous System , Encephalomyelitis , Meningoencephalitis , Humans , Animals , Dogs , Glial Fibrillary Acidic Protein/metabolism , Encephalomyelitis/pathology , Astrocytes/pathology , Autoimmune Diseases of the Nervous System/cerebrospinal fluid , Autoimmune Diseases of the Nervous System/therapy , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/pathology , AutoantibodiesABSTRACT
We have read with interest the article by Watroba and Bryda on a new-born male with SARS-CoV-2 associated meningo-encephalitis, post-inflammatory hydrocephalus and seizures [1]. Neuro-COVID in this patient was treated with a polypragmatic approach, including phenobarbital, acetazolamide, fluconazole, acyclovir, cefotaxime, and vancomycin [1]. The study is appealing but has limitations that raise concerns and should be discussed.
Subject(s)
COVID-19 , Meningoencephalitis , SARS-CoV-2 , Humans , Male , Acetazolamide/therapeutic use , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/drug therapy , Meningoencephalitis/virology , SARS-CoV-2/isolation & purification , SeizuresABSTRACT
Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Meningoencephalitis , Aged , Carcinoma, Renal Cell/drug therapy , Female , Humans , Immune Checkpoint Inhibitors , Interleukin-6 , Ipilimumab/adverse effects , Kidney Neoplasms/drug therapy , Leukocytosis/chemically induced , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/chemically induced , Meningoencephalitis/diagnosis , Methylprednisolone , Middle Aged , Nivolumab/adverse effects , Reflex, AbnormalABSTRACT
BACKGROUND: Cystatin C has neuroprotective and immunomodulatory effects on the central nervous system. However, the role of cerebrospinal fluid (CSF) cystatin C in anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) remains unknown. METHODS: In this study, CSF levels of cystatin C were determined in 73 patients with anti-NMDARE; 496 patients with other neurological diseases, comprising 108 with neuromyelitis optica, 77 with multiple sclerosis, 71 with schizophrenia, 68 with cryptococcus meningitis or meningoencephalitis, 43 with tuberculous meningitis or meningoencephalitis, 43 with bacterial meningitis or meningoencephalitis (BM), 35 with Guillain-Barré syndrome, 23 with spinal cord injury (SCI), 14 with amyotrophic lateral sclerosis (ALS), and 14 with idiopathic epilepsy; and 136 control patients with non-inflammatory diseases. The associations of CSF cystatin C with anti-NMDARE and its clinical parameters were evaluated. RESULTS: CSF cystatin C levels were significantly lower in patients with anti-NMDARE than in patients with BM, SCI, and ALS, especially among those with poor functional status (modified Rankin Scale [mRS] ≥4). CSF cystatin C levels were also significantly lower in anti-NMDARE patients with poor functional status (mRS ≥4) than in those with good functional status (mRS <4). CSF cystatin C levels were significantly associated with mRS scores and CSF white blood cell counts in anti-NMDARE patients. CONCLUSIONS: CSF levels of cystatin C are decreased in anti-NMDARE patients and negatively associated with disease severity.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Cystatin C , Nervous System Diseases , Amyotrophic Lateral Sclerosis/cerebrospinal fluid , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/cerebrospinal fluid , Cystatin C/cerebrospinal fluid , Humans , Meningoencephalitis/cerebrospinal fluid , Nervous System Diseases/cerebrospinal fluid , Neuromyelitis Optica/cerebrospinal fluidABSTRACT
Viral meningoencephalitis is one of the most important diseases that most commonly affect children. In many cases of viral meningoencephalitis, the underlying cause of the disease is not identified, raising the possibility of a variety of pathogens that are not routinely tested. Bocaviruses belong to a newly identified class of viruses that have been reported in some studies to be associated with viral encephalitis. In the present study, we investigated the prevalence of bocaviruses and other viruses in the patients suspected of having viral encephalitis and their associations with various demographic and clinical variables. Two hundred patients with suspected viral meningoencephalitis referred to Children's Medical Center were studied from 2019 to 2020. Age, sex, length of hospitalization, and course of the disease were gathered. Cerebrospinal fluid (CSF) samples were taken from the patients and subjected to biochemical examinations and PCR to identify the underlying cause. Bocaviruses were detected in none of the DNA samples extracted from the CSF specimens. The most identified organisms were mumps and enteroviruses. In 92% of cases, the underlying cause was not identified. PCR-based identification of the underlying causes of viral meningoencephalitis in CSF specimens was not successful in most cases. Bocavirus was not found in any of the collected CSF samples. Further studies are required for drawing more accurate conclusions.
Subject(s)
Encephalitis, Viral , Human bocavirus , Meningitis, Viral , Meningoencephalitis , Cerebrospinal Fluid , Child , Human bocavirus/genetics , Humans , Iran/epidemiology , Meningitis, Viral/cerebrospinal fluid , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/epidemiology , Polymerase Chain ReactionABSTRACT
BACKGROUND AND PURPOSE: Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. METHODS: Viral clearance was investigated in a patient with rituximab-induced B-cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi-quantitative E13 viral load measurements by real-time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. RESULTS: Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. CONCLUSION: In this report of a patient with rituximab-associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.
Subject(s)
Echovirus Infections , Enterovirus Infections , Meningitis, Aseptic , Meningoencephalitis , Myositis , Antiviral Agents , Echovirus Infections/cerebrospinal fluid , Enterovirus B, Human , Fluoxetine/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/drug therapy , Rituximab/therapeutic useABSTRACT
BACKGROUND: Necrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested. HYPOTHESIS/OBJECTIVE: Pug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME. ANIMALS: Thirty-six pug dogs less than 4 years of age asymptomatic for NME. METHODS: Prospective observational cohort study with germline genome-wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination. RESULTS: The overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at-risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at-risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.
Subject(s)
Dog Diseases , Meningoencephalitis , Animals , Dogs , Dog Diseases/cerebrospinal fluid , Dog Diseases/diagnosis , Dog Diseases/genetics , Gene Frequency , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/genetics , Meningoencephalitis/veterinary , Phenotype , Prospective StudiesABSTRACT
Objective: To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children. Methods: Children hospitalized in the Department of Neurology, Hunan Children's Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed. Results: A total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff's brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman's rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions. Conclusions: The disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes.
Subject(s)
Autoimmune Diseases of the Nervous System/immunology , Glial Fibrillary Acidic Protein/immunology , Immunoglobulin G/immunology , Adolescent , Autoimmune Diseases of the Nervous System/blood , Autoimmune Diseases of the Nervous System/cerebrospinal fluid , Autoimmune Diseases of the Nervous System/physiopathology , Child , Child, Preschool , Electroencephalography , Encephalomyelitis/blood , Encephalomyelitis/cerebrospinal fluid , Encephalomyelitis/immunology , Encephalomyelitis/physiopathology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Infant , Male , Meningoencephalitis/blood , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/immunology , Meningoencephalitis/physiopathology , Myelitis/blood , Myelitis/cerebrospinal fluid , Myelitis/immunology , Myelitis/physiopathology , Retrospective StudiesABSTRACT
RATIONALE: Aseptic meningoencephalitis is a rare central nervous system complication of relapsing polychondritis (RP). PATIENT: We report a 61-year-old Japanese male patient with spiking fever and impaired consciousness. Neurological examination revealed meningealirritation, and cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis with elevated protein (199âmg/dL) and interleukin-6 (3810âpg/mL). Serological analysis showed high levels of anti-type II collagen antibodies, and the result of auricular biopsy was consistent with the diagnosis of RP showing cartilage degeneration surrounded by inflammatory cell infiltrations. DIAGNOSIS: A clinical diagnosis of RP was made according to the diagnostic criteria established by MacAdams et al. INTERVENTION: Steroid pulse therapy (methylprednisolone 1000âmg, consecutive 3âdays) followed by oral prednisolone (60âmg/day) resolved the patient's high fever and disturbance of consciousness. OUTCOMES: The patient rapidly improved after steroid treatments and has a normal quality of life under the maintenance dose of steroid plus methotrexate (4âmg/week). LESSONS: RP-associated meningoencephalitis is a rare complication with significant morbidity and mortality. It should be considered and differentiated in patients with RP with unexplained spiking fever and impaired consciousness. In addition, the assessment of cerebrospinal fluid interleukin-6 levels may be useful to investigate the disease activity of RP-related meningoencephalitis. Further prospective studies are required to confirm this result.
Subject(s)
Meningoencephalitis/etiology , Polychondritis, Relapsing/complications , Glucocorticoids/administration & dosage , Humans , Interleukin-6/cerebrospinal fluid , Leukocytosis/cerebrospinal fluid , Leukocytosis/complications , Male , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/therapy , Methylprednisolone/administration & dosage , Middle Aged , Polychondritis, Relapsing/cerebrospinal fluid , Polychondritis, Relapsing/therapyABSTRACT
Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.
Subject(s)
Chemokine CCL7/genetics , Chemokine CXCL12/genetics , Encephalitis, Tick-Borne/genetics , Macrophages/virology , Meningoencephalitis/genetics , Monocytes/virology , Adolescent , Adult , Aged , Aged, 80 and over , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/virology , Case-Control Studies , Central Nervous System/immunology , Central Nervous System/metabolism , Central Nervous System/virology , Chemokine CCL20/blood , Chemokine CCL20/cerebrospinal fluid , Chemokine CCL20/genetics , Chemokine CCL7/blood , Chemokine CCL7/cerebrospinal fluid , Chemokine CXCL12/blood , Chemokine CXCL12/cerebrospinal fluid , Chemotaxis/immunology , Encephalitis, Tick-Borne/blood , Encephalitis, Tick-Borne/cerebrospinal fluid , Encephalitis, Tick-Borne/virology , Female , Gene Expression Regulation , Humans , Macrophages/immunology , Male , Meningoencephalitis/blood , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/virology , Middle Aged , Monocytes/immunology , Retrospective StudiesABSTRACT
Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82-6190.50; serum median 24.48, IQR 11.93-49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.
Subject(s)
Cytokines/cerebrospinal fluid , Meningitis/immunology , Meningoencephalitis/immunology , West Nile Fever/immunology , West Nile virus/immunology , Aged , Cytokines/blood , Cytokines/immunology , Female , Humans , Interleukin-17/blood , Interleukin-17/cerebrospinal fluid , Interleukin-17/immunology , Interleukin-4/blood , Interleukin-4/cerebrospinal fluid , Interleukin-4/immunology , Male , Meningitis/blood , Meningitis/cerebrospinal fluid , Meningitis/virology , Meningoencephalitis/blood , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/virology , Middle Aged , Th17 Cells/immunology , West Nile Fever/genetics , West Nile Fever/virology , West Nile virus/genetics , West Nile virus/physiologySubject(s)
Astrocytes/pathology , Brain/diagnostic imaging , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/diagnostic imaging , Spinal Cord/diagnostic imaging , Adrenal Cortex Hormones/pharmacology , Autoantibodies/cerebrospinal fluid , Brain/drug effects , Brain/metabolism , Female , Humans , Magnetic Resonance Imaging/methods , Meningoencephalitis/drug therapy , Middle Aged , Spinal Cord/drug effects , Spinal Cord/metabolismABSTRACT
BACKGROUND: Metagenomic next-generation sequencing offers an unbiased approach to identifying viral pathogens in cerebrospinal fluid of patients with meningoencephalitis of unknown etiology. METHODS: In an 11-month case series, we investigated the use of cerebrospinal fluid metagenomic next-generation sequencing to diagnose viral infections among pediatric hospitalized patients presenting with encephalitis or meningoencephalitis of unknown etiology. Cerebrospinal fluid from patients with known enterovirus meningitis were included as positive controls. Cerebrospinal fluid from patients with primary intracranial hypertension were included to serve as controls without known infections. RESULTS: Cerebrospinal fluid metagenomic next-generation sequencing was performed for 37 patients. Among 27 patients with encephalitis or meningoencephalitis, 4 were later diagnosed with viral encephalitis, 6 had non-central nervous system infections with central nervous system manifestations, 6 had no positive diagnostic tests, and 11 were found to have a noninfectious diagnosis. Metagenomic next-generation sequencing identified West Nile virus (WNV) in the cerebrospinal fluid of 1 immunocompromised patient. Among the 4 patients with known enterovirus meningitis, metagenomic next-generation sequencing correctly identified enteroviruses and characterized the viral genotype. No viral sequences were detected in the cerebrospinal fluid of patients with primary intracranial hypertension. Metagenomic next-generation sequencing also identified sequences of nonpathogenic torque Teno virus in cerebrospinal fluid specimens from 13 patients. CONCLUSIONS: Our results showed viral detection by cerebrospinal fluid metagenomic next-generation sequencing only in 1 immunocompromised patient and did not offer a diagnostic advantage over conventional testing. Viral phylogenetic characterization by metagenomic next-generation sequencing could be used in epidemiologic investigations of some viral pathogens, such as enteroviruses. The finding of torque Teno viruses in cerebrospinal fluid by metagenomic next-generation sequencing is of unknown significance but may merit further exploration for a possible association with noninfectious central nervous system disorders.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/virology , Metagenomics/methods , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Meningoencephalitis/geneticsABSTRACT
BACKGROUND: Streptococcus suis meningoencephalitis is a zoonotic disease that mostly infects slaughterhouse workers. Rapid diagnosis of Streptococcus suis meningoencephalitis is critical for effective clinical management of this condition. However, the current diagnostic techniques are not effective for early diagnosis of this condition. To the best of our knowledge, the use of cerebrospinal fluid metagenomic next generation sequencing in the diagnosis of Streptococcus suis meningoencephalitis has been rarely reported. CASE PRESENTATION: Here, we report a case of Streptococcus suis meningoencephalitis in a 51-year-old female patient. The patient had a history of long-term contact with pork and had a three-centimeter-long wound on her left leg prior to disease onset. Conventional tests, including blood culture, gram staining and cerebrospinal fluid culture, did not reveal bacterial infection. However, Streptococcus suis was detected in cerebrospinal fluid using metagenomic next generation sequencing. CONCLUSIONS: Metagenomic next generation sequencing is a promising approach for early diagnosis of central nervous system infections. This case report indicates that cases of clinical meningeal encephalitis of unknown cause can be diagnosed through this method.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/diagnosis , Streptococcal Infections/cerebrospinal fluid , Streptococcal Infections/diagnosis , Streptococcus suis/genetics , Zoonoses/cerebrospinal fluid , Zoonoses/diagnosis , Animals , Anti-Bacterial Agents/therapeutic use , Ceftazidime/therapeutic use , Early Diagnosis , Encephalitis , Female , Follow-Up Studies , Humans , Meningoencephalitis/drug therapy , Meningoencephalitis/microbiology , Middle Aged , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Treatment Outcome , Zoonoses/drug therapy , Zoonoses/microbiologyABSTRACT
The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case-control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.
Subject(s)
Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Meningoencephalitis/virology , Neopterin/cerebrospinal fluid , Virus Diseases/cerebrospinal fluid , Adolescent , Case-Control Studies , Child , Child, Preschool , Chromatography, High Pressure Liquid , Female , Humans , Infant , Infant, Newborn , Male , Meningoencephalitis/cerebrospinal fluid , Retrospective Studies , Young AdultABSTRACT
We prepared a newer growth medium, banana peel extract agar (BPEA) containing the extracts of chopped banana peels for the selective cultivation of Cryptococcus neoformans. Over the medium, the growth resulted in the development of light to the dark brown coloured colonies indicating the chromogenic potential of the BPEA. The organism grown over BPEA was subsequently confirmed as C. neoformans by phenotypic as well as by molecular method. This medium, being cost-effective, may be used in resource-poor settings of the developing or underdeveloped countries for selective isolation of C. neoformans.
Subject(s)
Bacteriological Techniques/methods , Cryptococcus neoformans/growth & development , Cryptococcus neoformans/isolation & purification , Culture Media/chemistry , Musa/chemistry , Plant Extracts/chemistry , Agar , Cerebrospinal Fluid/microbiology , Cryptococcosis/cerebrospinal fluid , Cryptococcosis/diagnosis , Cryptococcosis/microbiology , Cryptococcus neoformans/genetics , DNA, Bacterial/isolation & purification , Meningoencephalitis/cerebrospinal fluid , Meningoencephalitis/diagnosis , Meningoencephalitis/microbiologyABSTRACT
Introducción: la meningoencefalitis eosinofílica es una enfermedad inflamatoria infecciosa reportada en Cuba desde la década de los ochenta del siglo pasado y actualmente extendida al continente americano. Es producida por el parásito Angiostrongylus cantonensis. Objetivo: determinar si existen diferencias entre los pacientes que sufrieron meningoencefalitis eosinofílica antes y después de la introducción del caracol gigante africano. Métodos: se estudiaron un total de 19 muestras de líquido cefalorraquídeo y suero tomadas simultáneamente a cada paciente diagnosticados con meningoencefalitis eosinofílica, perteneciente a la seroraquioteca del Laboratorio Central del Líquido Cefalorraquídeo (LABCEL). Para la determinación de las proteínas albúmina e IgG se empleó como método de laboratorio la inmunodifusión radial. Resultados: el 14 por ciento de los pacientes fueron adultos antes de la aparición de este molusco, en contraste con el momento actual, donde el 50 por ciento son pacientes con edades superiores a 18 años. El porcentaje de síntesis de IgG intratecal media fue mayor en los enfermos actuales, aunque no de manera significativa. Conclusiones: . existen diferencias antes y después de la aparición del caracol gigante africano dado por la respuesta de síntesis intratecal en los pacientes asociados con el molusco que denota una mayor agresividad del parásito. La edad promedio mayor de los enfermos confirma que estos son los que más manipulan y dispersan el molusco(AU)
Introduction: eosinophilic meningoencephalitis is an infectious inflammatory disease reported in Cuba since the 1980s and currently extended to the American continent. This condition is caused by the parasite Angiostrongylus cantonensis. Objective: determine whether there are differences between the patients suffering from eosinophilic meningoencephalitis before and after the introduction of the giant African snail. Methods: a study was conducted of a total 19 cerebrospinal fluid and serum samples taken simultaneously from each of the patients diagnosed with eosinophilic meningoencephalitis and kept at the sample collection of the Central Cerebrospinal Fluid Laboratory (LABCEL). Radial immunodiffusion was the laboratory method used for determination of the proteins albumin and IgG. Results: of the patients studied, 14 percent were adults before the appearance of this mollusc, in contrast with the present moment, when 50 percent are patients aged over 18 years. The percentage of mean intrathecal synthesis of IgG was higher in the current sufferers, though not significantly. Conclusions: there are differences before and after the appearance of the giant African snail, given the intrathecal synthesis response of patients associated to the mollusc, which denotes greater aggressiveness by the parasite. The higher mean age of sufferers confirms that these are the ones who most often handle and disperse the mollusc(AU)
Subject(s)
Humans , Strongylida Infections/complications , Meningoencephalitis/cerebrospinal fluid , Snails/parasitology , Angiostrongylus cantonensis/pathogenicity , LaboratoriesABSTRACT
Immune checkpoint inhibitors (ICIs) represent a major development in cancer treatment, allowing for improved survival and disease control in an expanding number of cancer types. Due to their mechanism of disrupting immunologic homeostasis, ICIs are frequently associated with adverse effects, termed immune related adverse effects (irAE). These side effects can affect any organ system, including the central and peripheral nervous systems. We present a case of a 47 year old man with stage IIIc metastatic melanoma who received 3 cycles of nivolumab (a monoclonal antibody inhibitor of programmed cell death protein 1 (PD-1)). After completing the third cycle, he presented with a meningoencephalitis clinical picture with an inflammatory cerebrospinal fluid (CSF) and normal MRI. He was found to have a positive anti-glial fibrillary acidic protein (GFAP) autoantibody in his CSF by immunofluorescent assay (IFA) and cell based assay (CBA) which confirmed a diagnosis of anti-GFAP autoimmune encephalitis. He was treated with immunotherapy and made a full recovery. In this report, we present the first reported case of anti-GFAP autoimmune encephalitis associated with ICI therapy and provide a brief review of the literature.