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Cureus Sep 2023Introduction The treatments and prognosis of bacterial meningitis differ greatly from those of aseptic meningitis, making early identification and differentiation...
Introduction The treatments and prognosis of bacterial meningitis differ greatly from those of aseptic meningitis, making early identification and differentiation essential. Several different clinical prediction rules have been developed to distinguish bacterial meningitis from aseptic meningitis. We sought to validate one clinical prediction rule for pediatric patients utilizing a centralized data warehouse that collects daily data from 184 hospitals across the United States. Methods We retrospectively collected data on all patients aged 29 days to 14 years who presented to Hospital Corporation of America (HCA) Healthcare hospitals from January 1, 2016, to May 31, 2021, with a diagnosis of meningitis. Our study replicated the original study of the meningitis score for emergencies (MSE) for the pediatric clinical prediction rule and assigned 3 points for procalcitonin (PCT) >1.2 ng/dL, 2 points for CSF protein >80 mg/dL, and 1 point for each of the other variables of C-reactive protein (CRP) >40 mg/L and CSF absolute neutrophil count >1000 cells per mm. Patients were categorized either as having bacterial or aseptic meningitis. Using the clinical prediction rule, a calculation of the sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic (ROC) curve was performed. Results The optimum test characteristic was found to have a score of ≥ 3, showing a sensitivity of 92.86% (95% CI, 83.3-100), a specificity of 65.22% (95% CI, 51.5-79), a positive predictive value of 61.90% (95% CI, 47.2-76.6), and a negative predictive value of 93.75% (95% CI, 85.4-100). The ROC curve from this study showed an area under the curve (AUC) of 0.7892 (95% CI, 0.681-0.897). Conclusion Our study validated a high sensitivity for distinguishing bacterial meningitis from aseptic meningitis, suggesting the clinical prediction rule has clinical utility as a predictive screening tool. Although the original MSE advised a cutoff score of ≥1, our study suggests that a score ≥3 would give the best test performance.
PubMed: 37881396
DOI: 10.7759/cureus.45829 -
Heliyon Oct 2023Glial fibrillary acidic protein astrocytopathy is a form of autoimmune meningoencephalomyelitis. The presence of antibodies in spinal fluid against glial fibrillary...
Glial fibrillary acidic protein astrocytopathy is a form of autoimmune meningoencephalomyelitis. The presence of antibodies in spinal fluid against glial fibrillary acidic protein is necessary to diagnose the disease. There is no standard treatment and few cases of glial fibrillary acidic protein astrocytopathy have been reported. A 31-year-old healthy Japanese man presented to our emergency department with a 7-day history of fever and headache. He was in good general condition, without abnormalities on physical examination, and a general hematological examination revealed hyponatremia (130 mEq/L). Five days later, he was followed up and new subjective symptoms were noted: tremor in the right hand, constipation, sweating, and lightheadedness. Cerebrospinal fluid examination revealed a cell count of 57/μL (96 % mononuclear cells, 4 % multinuclear cells), elevated protein level (103 mg/dL), elevated adenosine deaminase level (15.0 U/L), negative polymerase chain reaction test results for herpes simplex virus and , negative cerebrospinal fluid culture, and negative cerebrospinal fluid anti-acid bacteria culture, indicating aseptic meningitis. T1-weighted contrast-enhanced magnetic resonance imaging of the head showed a linear contrast effect perpendicular to the lateral ventricular wall and along the perivascular vessels spreading radially. Based on the presence of hyponatremia, history of movement disorder and autonomic symptoms, high adenosine deaminase level in cerebrospinal fluid, and findings on contrast-enhanced magnetic resonance imaging of the head, we suspected glial fibrillary acidic protein astrocytopathy and assessed anti-glial fibrillary acidic proteinαantibody in cerebrospinal fluid, which was positive, and diagnosed glial fibrillary acidic protein astrocytopathy. After careful follow-up with symptomatic treatment without immunosuppressive therapy, the fever, headache, tremor, and autonomic symptoms were improved over time. Contrast-enhanced magnetic resonance imaging of the head and findings of cerebrospinal fluid also showed improvement. glial fibrillary acidic protein astrocytopathy should be a differential diagnosis in patients with aseptic meningitis with movement disorders or autonomic symptoms and elevated cerebrospinal fluid adenosine deaminase. Careful follow-up without immunosuppressive treatment should be considered for patients with minimal neurologic symptoms as glial fibrillary acidic protein astrocytopathy may have a self-limiting course and resolve.
PubMed: 37867900
DOI: 10.1016/j.heliyon.2023.e20912 -
Frontiers in Pediatrics 2023This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg)...
Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study.
INTRODUCTION
This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged < 12 years) with primary immunodeficiency diseases (PID) ( = 32) or immune thrombocytopenia (ITP) ( = 27) in France.
METHODS
The primary objective of the study was to assess the safety and tolerability of Clairyg®, recording all serious and non-serious adverse events (AEs), whether related (rAEs) or not related to the product. Secondary objectives aimed at evaluating the administration of Clairyg® under routine conditions and the available efficacy data to better document the benefit/risk ratio in this pediatric population. An exploratory objective was added to evaluate the potential factors associated with the occurrence of rAEs. Patients received Clairyg® according to the approved dosage under normal conditions of prescriptions over a median follow-up period of 11.8 months.
RESULTS
A total of 549 infusions (PID: = 464 and ITP: = 85), were administered, of which 58.8% were preceded by premedication. The most frequent rAEs were headache, vomiting, and pyrexia in both indications. Most of them were considered non-serious and mild or moderate in intensity. A severe single rAE was observed (aseptic meningitis) in a 4-year-old girl presenting with chronic ITP. The exploratory multivariate analysis of potential co-factors showed that the occurrence of rAEs is significantly linked to high IVIg doses and possibly to female gender. The annualized rate of serious bacterial infections was 0.11 for patients with PID. For patients with ITP, 74.1% experienced at least one bleeding episode during the follow-up, mostly a cutaneous one, and none had gastrointestinal, genitourinary, or central nervous system bleeding.
CONCLUSION
Clairyg® was well tolerated and allowed for control of serious bacterial infection in PID and serious bleeding in ITP, which are the main complications in these respective pediatric disorders. No new safety signal was detected in children less than 12 years-old in real-life conditions of use.
PubMed: 37849499
DOI: 10.3389/fped.2023.1260296 -
Case Reports in Pediatrics 2023. Differentiating Crohn's disease (CD) and Behçet's disease (BD) with gastrointestinal (GI) manifestations can be clinically challenging, as current diagnostic criteria...
. Differentiating Crohn's disease (CD) and Behçet's disease (BD) with gastrointestinal (GI) manifestations can be clinically challenging, as current diagnostic criteria are not clear between both conditions and multiple symptoms could overlap. . The patient is an 8-year-old boy of Brazilian descent, who initially presented with a 1-year history of painful oral ulcers. Before presenting to the hospital, he had been treated for periodic fever, aphthous stomatitis, pharyngitis, and adenitis and placed on steroids, with relapsing symptoms on attempts to wean the doses. The initial workup was largely unremarkable. Buccal biopsies showed no granulomas, and the ophthalmologic exam was normal. Infectious and rheumatological tests were negative. Prometheus IBD sgi testing showed a pattern consistent with CD; however, the patient had multiple negative endoscopies, colonoscopies, and capsule endoscopies. He developed intermittent bloody stools and severe malnutrition and did not respond to infliximab, colchicine, or methotrexate. After a large GI bleed, a 4th colonoscopy was performed, which showed large round ulcers in the terminal ileum, and no granulomas. He was started on ustekinumab with clinical improvement. One month later, he developed bilateral hip effusion and meningismus, being diagnosed with aseptic meningitis secondary to COVID-19. He improved, but in one month developed worsening symptoms, and MRV showed extensive venous sinus thrombosis. The patient was started on enoxaparin, methylprednisolone, and colchicine, with resolution of the thrombus on a 3-month follow-up. The patient's overall symptoms remained controlled with clinical and biochemical remission on monthly ustekinumab. . Our patient had a challenging clinical course, with nonspecific systemic and intestinal manifestations which proved difficult to differentiate between BD and CD. Given endoscopic findings and the worsening of an auto-inflammatory reaction in the central nervous system after COVID-19 in a patient with controlled GI symptoms, the most likely diagnosis is BD.
PubMed: 37830113
DOI: 10.1155/2023/4705638 -
IDCases 2023A 36-year-old male with headaches was empirically treated for herpes simplex virus meningitis; CSF PCR testing later confirmed varicella zoster virus meningitis....
A 36-year-old male with headaches was empirically treated for herpes simplex virus meningitis; CSF PCR testing later confirmed varicella zoster virus meningitis. Valacyclovir was increased to 2 g QID for remaining duration of therapy with full recovery. This case highlights the importance of comprehensive testing and proper treatment adjustment for rarer etiologies of aseptic meningitis.
PubMed: 37786647
DOI: 10.1016/j.idcr.2023.e01899 -
Current Research in Microbial Sciences 2023Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and...
Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.
PubMed: 37767059
DOI: 10.1016/j.crmicr.2023.100203 -
Brain Sciences Sep 2023Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are... (Review)
Review
Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reaction. On the other hand, autoimmune diseases result from dysregulation of the adaptive immune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflammatory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.
PubMed: 37759952
DOI: 10.3390/brainsci13091351 -
The Keio Journal of Medicine Dec 2023We encountered a-27-year-old female patient who developed refractory severe headache and photophobia after the first dose of COVID-19 vaccine. Despite her prior history... (Review)
Review
We encountered a-27-year-old female patient who developed refractory severe headache and photophobia after the first dose of COVID-19 vaccine. Despite her prior history of migraine, we diagnosed COVID-19 vaccine-induced aseptic meningitis. Symptoms were significantly resolved after methylprednisolone therapy. On reviewing the literature, we could find only nine similar cases, with over half of them affecting women aged 20-40 years. Although uncommon, aseptic meningitis should be suspected in patients with persistent or delayed onset of headache following COVID-19 vaccination.
Topics: Female; Humans; BNT162 Vaccine; COVID-19; Headache; Meningitis, Aseptic; Vaccination; Adult
PubMed: 37743529
DOI: 10.2302/kjm.2022-0034-CR -
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 -
Cureus Aug 2023Sarcoidosis is an immune-mediated disease that can involve multiple systems. Sarcoidosis of the nervous system or neurosarcoidosis may present as cranial mononeuropathy,...
Sarcoidosis is an immune-mediated disease that can involve multiple systems. Sarcoidosis of the nervous system or neurosarcoidosis may present as cranial mononeuropathy, hypothalamic involvement, aseptic meningitis, granulomatous inflammation in the brain parenchyma or spinal cord, peripheral neuropathy, and, in rare cases, as myopathy and benign intracranial hypertension. The most common cranial nerve involvement is the facial nerve, which can present as unilateral or bilateral facial nerve palsy, often with recurrent episodes. Involvement of other cranial nerves such as the second and eighth cranial nerves has also been reported. Granulomatous inflammation in the spinal cord presents as myelopathy or radiculopathy. Peripheral neuropathy can manifest as mononeuropathy, mononeuritis multiplex, or generalized sensory-motor neuropathy. Carpal tunnel syndrome is more common in patients with sarcoidosis compared to the general population. Here, we describe the case of a 40-year-old female who presented with heaviness of the head and blurred vision, with a prior history of left-sided Bell's palsy. Bilateral papilledema was observed during the fundus examination. MRI of the brain revealed signs suggestive of benign intracranial hypertension. The cerebrospinal fluid (CSF) opening pressure was measured at 40 cmH2O. Biopsy of bilateral hilar lymphadenopathy indicated granulomatous inflammation consistent with sarcoidosis. The patient was started on steroids and acetazolamide, and she had a dramatic improvement in symptoms.
PubMed: 37701004
DOI: 10.7759/cureus.43363