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European Journal of Neurology Jul 2024This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A), a rare but severe neuroinflammatory disorder, to facilitate early diagnosis and appropriate treatment.
METHODS
A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)-conforming systematic review and meta-analysis was performed on all available data from January 2016 to June 2023. Clinical and neuroimaging phenotypes were extracted for both adult and paediatric forms.
RESULTS
A total of 93 studies with 681 cases (55% males; median age = 46, range = 1-103 years) were included. Of these, 13 studies with a total of 535 cases were eligible for the meta-analysis. Clinically, GFAP-A was often preceded by a viral prodromal state (45% of cases) and manifested as meningitis, encephalitis, and/or myelitis. The most common symptoms were headache, fever, and movement disturbances. Coexisting autoantibodies (45%) and neoplasms (18%) were relatively frequent. Corticosteroid treatment resulted in partial/complete remission in a majority of cases (83%). Neuroimaging often revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities (74%) as well as perivascular (45%) and/or leptomeningeal (30%) enhancement. Spinal cord abnormalities were also frequent (49%), most commonly manifesting as longitudinally extensive myelitis. There were 88 paediatric cases; they had less prominent neuroimaging findings with lower frequencies of both T2/FLAIR hyperintensities (38%) and contrast enhancement (19%).
CONCLUSIONS
This systematic review and meta-analysis provide high-level evidence for clinical and imaging phenotypes of GFAP-A, which will benefit the identification and clinical workup of suspected cases. Differential diagnostic cues to distinguish GFAP-A from common clinical and imaging mimics are provided as well as suitable magnetic resonance imaging protocol recommendations.
Topics: Humans; Astrocytes; Autoantibodies; Autoimmune Diseases of the Nervous System; Glial Fibrillary Acidic Protein; Neuroimaging; Neuroinflammatory Diseases; Phenotype
PubMed: 38506182
DOI: 10.1111/ene.16284 -
The New Zealand Medical Journal Mar 2024
Topics: Humans; New Zealand; Meningitis, Bacterial; Encephalitis, Viral; Meningitis
PubMed: 38513208
DOI: 10.26635/6965.6468 -
Frontiers in Microbiology 2023Viral and bacterial infections are major causes of morbidity and mortality worldwide. The oropharyngeal microbiome could play an important role in preventing invasion of... (Review)
Review
CONTEXT
Viral and bacterial infections are major causes of morbidity and mortality worldwide. The oropharyngeal microbiome could play an important role in preventing invasion of viral and bacterial pathogens by modulating its content and the host's innate immune response. Next Generation Sequencing (NGS) technologies now enable in-depth study of the genomes of microbial communities. The objective of this review is to highlight how metagenomics has contributed to establish links between changes in the oropharyngeal microbiome and emergence of bacterial and viral diseases.
METHOD
Two search engines, PubMed and Google scholar were used with filters to focus searches on peer-reviewed original articles published between January 2010 and September 2022. Different keywords were used and only articles with metagenomic approaches were included.
RESULTS
This review shows that there were few articles studying the link between oropharyngeal microbiome and infectious diseases. Studies on viruses using metagenomic techniques have been growing exponentially in recent years due to the Covid-19 pandemic. This review shows that most studies still focus on the basic identification of microorganisms in different disease states and multiple microorganisms ( sp.), have been associated with development of infections such as childhood wheezing, , Covid-19, , , and .
CONCLUSION
The oropharyngeal microbiome, despite its importance, remains poorly studied. A limited number of articles were identified but this number has increased exponentially since 2020 due to research conducted on Covid-19. These studies have shown that metagenomic has contributed to the unbiased identification of bacteria that could be used as biomarkers of various diseases and that further research is now needed to capitalize on those findings for human health benefit.
PubMed: 38163063
DOI: 10.3389/fmicb.2023.1292526 -
Pediatric Research Jan 2024Recent decades have witnessed the emergence and re-emergence of numerous medically important viruses that cause central nervous system (CNS) infections in children,... (Review)
Review
Recent decades have witnessed the emergence and re-emergence of numerous medically important viruses that cause central nervous system (CNS) infections in children, e.g., Zika, West Nile, and enterovirus/parechovirus. Children with immature immune defenses and blood-brain barrier are more vulnerable to viral CNS infections and meningitis than adults. Viral invasion into the CNS causes meningitis, encephalitis, brain imaging abnormalities, and long-term neurodevelopmental sequelae. Rapid and accurate detection of neurotropic viral infections is essential for diagnosing CNS diseases and setting up an appropriate patient management plan. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis/encephalitis. However, the expansion of test menu has led to new challenges in selecting appropriate tests and making accurate interpretation of test results. There are unmet gaps in development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses. Herein we will discuss the advances and challenges in the laboratory diagnosis of viral CNS infections in children. This review not only sheds light on selection and interpretation of a suitable diagnostic test for emerging/re-emerging neurotropic viruses, but also calls for more research on development and clinical utility study of novel molecular assays. IMPACT: Children with immature immune defenses and blood-brain barrier, especially neonates and infants, are more vulnerable to viral central nervous system infections and meningitis than adults. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis and encephalitis. There are unmet gaps in the development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses.
Topics: Adult; Infant; Infant, Newborn; Child; Humans; Viruses; Central Nervous System Infections; Central Nervous System Viral Diseases; Encephalitis; Meningitis; Clinical Laboratory Techniques; Zika Virus; Zika Virus Infection
PubMed: 38042947
DOI: 10.1038/s41390-023-02930-6 -
Infection Jun 2024To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome).
PURPOSE
To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome).
METHODS
Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020.
RESULTS
Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27-43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31-514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%).
CONCLUSIONS
Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.
Topics: Humans; Denmark; Female; Adult; Male; Radiculopathy; Cohort Studies; Urinary Retention; Herpesvirus 2, Human; Middle Aged; Lumbosacral Region; Herpes Zoster; Herpesvirus 3, Human
PubMed: 37917395
DOI: 10.1007/s15010-023-02113-9 -
Central Nervous System Agents in... Apr 2024Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs.
BACKGROUND
Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs.
OBJECTIVE
The aim of this study was to present a systematic review of the association between infections, seizures, and drugs.
METHODS
Through February 18, 2024, according to the PRISMA guidelines and based on the PICO standard format, relevant, in-depth consequent guide approach and evidence-based options were selected associated with a knowledgeable collection of current, high-quality manuscripts.
RESULTS
Imbalance between inhibitory and excitatory neurotransmitters due to infections, drugs such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, tramadol, venlafaxine, cyclosporine, tacrolimus, acyclovir, cellcept, the old generation of antiepileptic drugs, such as carbamazepine, phenytoin, and many other drugs could cause different stages of CNS disturbances ranging from seizure to encephalopathy. Infections could cause life-threatening status epilepticus by continuous unremitting seizures lasting longer than 5 minutes or recurrent seizures. Meningitis, tuberculosis, herpes simplex, cerebral toxoplasmosis, and many others could lead to status epilepticus. In fact, confusion, encephalopathy, and myoclonus were reported with drugs, such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, and others. Penicillin G was reported as having the greatest epileptogenic potential. A high dose, in addition to prolonged use of metronidazole, was reported with seizure infection. Meropenem could decrease the concentration of valproic acid. Due to the inhibition of cytochrome P450 3A4, the combination of clarithromycin and erythromycin with carbamazepine needs vigilant monitoring.
CONCLUSION
Due to changes in drug metabolism, co-administration of antiseizure drugs and antibiotics may lead to an enhanced risk of seizures. In patients with neurocysticercosis, cerebral malaria, viral encephalitis, bacterial meningitis, tuberculosis, and human immunodeficiency virus, the evidence-based study recommended different mechanisms mediating epileptogenic properties of toxins and drugs.
PubMed: 38676494
DOI: 10.2174/0118715249288932240416071636 -
The Pediatric Infectious Disease Journal May 2024Most childhood meningitis is viral in countries with widespread conjugate vaccine use. This study assessed clinical features and neurodevelopmental outcomes in preschool...
BACKGROUND
Most childhood meningitis is viral in countries with widespread conjugate vaccine use. This study assessed clinical features and neurodevelopmental outcomes in preschool children following enteroviral and parechoviral meningitis.
METHODS
Children 18-42 months of age in Canterbury, New Zealand were included, who had enterovirus (EV) or parechovirus (HPEV) meningitis from 2015 to 2021. Comprehensive neurodevelopmental assessments were completed by a psychologist using the Bayley Scale for Infant Development-3 (BSID-3). Mean composite and scaled scores and proportion below the cutoff were assessed in each domain. Clinical data was analyzed.
RESULTS
There were 79 children 18-42 months old with previous EV or HPEV meningitis. BSID assessments were completed for 33 children (55% male), median age 32 months, from 2019 to 2022 including 23 with EV and 10 HPEV meningitis. At diagnosis, 32 (97%) received intravenous/intramuscular antibiotics, and 6 received a fluid bolus. Parents reported developmental speech concerns in 6 children, and delayed motor milestones in 1 child. There was no reported sensorineural hearing loss. BSID mean composite scores were in the expected range for cognition 102 (confidence interval: 98-106), language 96 (93-100) and motor 102 (98-106) domains. Overall, 12/33 (36%) children had below expected scores in 1 developmental domain, including scores 1-2 SD below the normative mean for cognition (2/33; 6%), receptive language (6/33; 18%), expressive language (5/33; 15%) and gross motor (6/33; 18%). There were no differences between scores in EV and HPEV meningitis.
CONCLUSION
Following viral meningitis, more than a third of preschool children had a mild developmental delay with comprehensive neurodevelopmental assessment, suggesting targeted follow-up should be considered.
PubMed: 38754002
DOI: 10.1097/INF.0000000000004398 -
Parasitology Research Jan 2024Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic... (Review)
Review
Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic ameba of freshwater systems. PAM remains a neglected disease that disproportionately affects children in tropical and subtropical climates, with an estimated mortality rate of 95-98%. Due to anthropogenic climate change, the average temperature in the USA has increased by 0.72 to 1.06 °C in the last century, promoting the poleward spread of N. fowleri. PAM is often misdiagnosed as bacterial meningitis or viral encephalitis, which shortens the window for potentially life-saving treatment. Diagnosis relies on the patient's history of freshwater exposure and the physician's high index of suspicion, supported by cerebrospinal fluid studies. While no experimental trials have been conducted to assess the relative efficacy of treatment regimens, anti-amebic therapy with adjunctive neuroprotection is standard treatment in the USA. We performed a literature review and identified five patients from North America between 1962 and 2022 who survived PAM with various degrees of sequelae.
Topics: Child; Humans; Naegleria fowleri; Central Nervous System Protozoal Infections; Brain; Climate Change; Disease Progression
PubMed: 38182931
DOI: 10.1007/s00436-023-08094-w -
Pediatric Research Jan 2024Congenital infections can have devastating short- and long-term impacts on the developing fetus. Lymphocytic choriomeningitis virus (LCMV) is a zoonotic pathogen of... (Review)
Review
Congenital infections can have devastating short- and long-term impacts on the developing fetus. Lymphocytic choriomeningitis virus (LCMV) is a zoonotic pathogen of concern that causes a severe congenital syndrome but is under-recognized and under-studied. Herein we review data on the natural animal reservoirs of LCMV, modes of transmission to humans, seroprevalence of LCMV worldwide in both pregnant and non-pregnant individuals, mechanisms of viral dissemination to placenta and fetus, and impact of climate change on viral transmission. We highlight opportunities to enhance awareness of congenital LCMV and provide recommendations for prevention and monitoring among at-risk pregnant people. IMPACT: Key message of the article: LCMV is a zoonotic virus that poses a major threat to maternal-fetal health. Adds to the existing literature: We comprehensively address transmission of LCMV from the natural reservoir to the pregnant individual, placenta, and fetus. Impact: Available data call for enhanced patient and provider awareness about congenital LCMV during pregnancy, as well as a need for efforts to better define the seroprevalence and impact of congenital LCMV worldwide.
Topics: Pregnancy; Animals; Female; Humans; Lymphocytic choriomeningitis virus; Lymphocytic Choriomeningitis; Seroepidemiologic Studies; Placenta; Fetal Diseases
PubMed: 37857846
DOI: 10.1038/s41390-023-02859-w -
Frontiers in Pharmacology 2023Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced...
Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor used in B cell malignancy treatment and is generally well tolerated in most patients. Zanubrutinib-induced aseptic meningitis is currently not reported. Herein, we present the first case of zanubrutinib-induced aseptic meningitis. A 33-year-old woman was diagnosed with relapsed/refractory follicular lymphoma and subsequently developed aseptic meningitis after receiving zanubrutinib treatment. We reviewed the literature and uncovered the lack of current reports on zanubrutinib or other BTK inhibitor-induced aseptic meningitis. Moreover, we summarized cases on aseptic meningitis induced by common chemotherapy and targeted drugs used for hematological diseases. Drug-induced aseptic meningitis (DIAM) is a drug-induced meningeal inflammation. The possible pathogenesis is the direct stimulation of the meninges via intrathecal injection of chemotherapy drugs and immune hypersensitivity response caused by immunosuppressive drugs. It is more common in women with immune deficiency and mainly manifests as persistent headache and fever. Cerebrospinal fluid examinations mainly demonstrate a significant increase in cells and proteins. DIAM diagnosis needs to exclude bacterial, fungal, viral, and tuberculosis infections; neoplastic meningitis; and systemic diseases involving the meninges. The prognosis of DIAM is usually favorable, and physicians should detect and stop the causative drug. In conclusion, zanubrutinib-induced aseptic meningitis is a rare but serious complication, and physicians should be promptly aware of this adverse event to avoid serious consequences.
PubMed: 37727390
DOI: 10.3389/fphar.2023.1242491