Acute Aseptic Meningitis Temporally Associated with Intravenous Polyclonal Immunoglobulin Therapy: A Systematic Review.

An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.

Amoxicillin-induced aseptic meningitis: clinical features, diagnosis and management.

OBJECTIVES: The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. METHODS: AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. RESULTS: AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1-4 days after drug discontinuation in all patients. CONCLUSION: Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.

Immune-related aseptic meningitis and strategies to manage immune checkpoint inhibitor therapy: a systematic review.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) can induce adverse neurological effects. Due to its rarity as an adverse effect, meningitis has been poorly described. Therefore, meningitis diagnosis and management can be challenging for specialists. Moreover, meningitis can be an obstacle to resuming immunotherapy. Given the lack of alternatives, the possibility of reintroducing immunotherapy should be discussed on an individual basis. Here, we present a comprehensive systematic review of meningitis related to ICIs. REVIEW: We performed a search for articles regarding immune-related meningitis published in PubMed up to November 2021 with the MeSH terms "meningitis" and "immune checkpoint" using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized the studies not only by category but also based on whether it was a primary article or case report to provide a systematic overview of the subject. We reviewed a total of 38 studies and herein report the clinical experiences, pharmacovigilance data and group knowledge from these studies. CONCLUSION: This review summarizes the existing information on immune-related meningitis and the possibility of reintroducing immunotherapy after the development of central neurological side effects. To the best of our knowledge, there is little information in the literature to guide clinicians on decisions regarding whether immunotherapy should be continued after a neurological adverse event occurs, especially meningeal events. This review emphasizes the necessity of systematic examinations, steroid treatment (as a cornerstone of management) and the need for further exploratory studies to obtain a clearer understanding of how to better manage patients who experience these side effects. The findings summarized in this review can help provide guidance to practitioners who face this clinical situation.

Aseptic Meningitis Following the Second Dose of Comirnaty Vaccination in an Adolescent Patient: A Case Report.

Vaccination is currently the best strategy to control the coronavirus disease 2019 epidemic. This report describes a case of aseptic meningitis 3 weeks after administration of the second dose of Comirnaty. The patient recovered with conservative and symptomatic care after 5 days of admission. Surveillance of rare adverse events, including aseptic meningitis, and their management should be prompt and appropriate.

Spectrum of Complications in a Case of Intramedullary Dermoid.

BACKGROUND: Intramedullary spinal cord dermoid tumors are rare. Early diagnosis with appropriate imaging is of utmost importance for a good outcome. Gross total resection is the treatment of choice for optimal results. Neurosurgical intervention for any intramedullary lesion is fraught with problems because of the nature of the lesion and handling of the spinal cord, which is already compromised because of the intramedullary lesion. Recurrence of the intramedullary dermoid tumor is frequent because of incomplete resection of the tumor. Most commonly, patients present with worsening of neurologic deficits. Inadequate resection because of the fear of worsening the neurologic deficits is associated with significant complications. CASE DESCRIPTION: We report a case of an intramedullary dermoid tumor in a child that was associated with myriad of complications owing to incomplete resection of the tumor. The patient underwent multiple interventions at various centers which resulted in serious multiple complications before presenting at our center for further management. CONCLUSIONS: This report highlights the spectrum of complications that can develop in a patient varying from worsening of the deficits to meningitis and subsequent development of hydrocephalus.

Encephalitis and aseptic meningitis: short-term and long-term outcome, quality of life and neuropsychological functioning.

For those surviving encephalitis, the influence on daily life of patients and their relatives may be substantial. In contrast, the prognosis after aseptic meningitis (ASM) is considered good. In this prospective study in patients with encephalitis (n = 20) and ASM (n = 46), we show that both groups experienced reduced Health Related Quality of Life (HRQoL) at two months after discharge, and that workability was reduced in 37% of the patients with ASM. However, 12 months after discharge no neuropsychological deficits were detected in the ASM group, whereas patients with encephalitis had lower scores on tests of fine motor and psychomotor skills as well as on learning and memory. We also found that for patients with encephalitis, neopterin, as a marker of Th1 cell induced macrophage activation, and a putatively neurotoxic ratio of the kynurenine pathway (KP) measured during the acute phase was associated with lower HRQoL. Our data show that not only encephalitis, but also ASM has substantial short-term influence on HRQoL and workability. For patients with encephalitis we suggest a link between immune activation and activation of the KP during the acute phase with impaired HRQoL.

Our experience with using a uniform prophylactic protocol in neurosurgery: surgical-site infection did not occur in 272 operations.

PURPOSE: Surgical site infection (SSI) is a source of concern in any surgical procedure. Although studies with high numbers of patients are available, most of these studies were performed by different surgeons and the exact anti-SSI protocol is not mentioned or is not homogeneous in all patients. MATERIALS AND METHODS: We present the results of 272 cases where SSI was successfully prevented in our neurosurgical units and in this study we explain our institutional protocol for achieving this positive result. We included all neurosurgical procedures in our two centers that needed an operating room, undertaken between 9 November 2015 and 6 December 2016, retrospectively. Then we compare our results with the existing literature. RESULTS: We performed 272 neurosurgical procedures on 245 patients. 155 patients were male and 90 were female. We re-operated on 24 patients and 3 of them operated on three times in each instance case and others were operated on twice. The patient's ages ranged from 2 to 86years with the mean being 42.39 ± 19 years. The cranial site of surgery was more common (129 procedures, 47.4%) and overall 118 operations (43.4%) were accompanied with a prosthetic device placement. We performed 96 emergency procedures. The mean hospitalization time was 6.19 ± 6.77 days. We followed all patients for at least six months. There were no reports of SSI in our neurosurgical units. CONCLUSION: With a fixed protocol of antisepsis, hand protection and prophylactic antibiotics, there were achieved good results. We recommend the current protocol as an effective measure in the control of infection in the neurosurgical ward. However, further studies are needed with more patients and a stronger study design.

Aseptic central nervous system infections in adults: what predictor for unknown etiological diagnosis?

Despite the availability of nucleic acid amplification tests (NAATs), most of aseptic acute meningitides, encephalitides, and meningoencephalitides (AAMEMs) in adults remain of unknown etiology so far. To shed light on such topic, we aimed to evaluate potential predictors for AAMEMs of unknown origin. We collected retrospectively data from all consecutive cases of AAMEMs in adults discharged from an Italian referral hospital, from January 2004 to December 2016. Laboratory analysis included common immunometric methods and NAATs. Potential predictors for unknown etiology (age, seasonality, serum C-reactive protein value, antibiotic use before lumbar puncture, immunodeficiency conditions, clinical symptoms and signs) were evaluated by a logistic regression analysis model. A p value ≤ 0.05 was considered to indicate statistical significance. The study included 92 patients (median age 39 years; 54.3% males) affected by meningitis (n = 57), encephalitis (n = 25), and meningoencephalitis (n = 10). The identified agents that cause AAMEMs were herpesviruses (20.7%), enteroviruses (5.4%), tick-borne encephalitis virus (3.3%), influenza virus A (2.2%), West Nile virus (1.1%), and parvovirus B19 (1.1%), while 66.3% of cases were of unknown etiology. No predictor was found to be significantly associated with AAMEMs of unknown etiology. We suggest that potential infectious agents causing undiagnosed cases should be investigated among non-bacterial, non-opportunistic, and non-seasonal organisms.

Drug-induced aseptic meningitis: a mini-review.

Aseptic meningitis associates a typical clinical picture of meningitis with the absence of bacterial or fungal material in the cerebrospinal fluid. Drug-induced aseptic meningitis (DIAM) may be due to two mechanisms: (i) a direct meningeal irritation caused by the intrathecal administration of drugs and (ii) an immunologic hypersensitivity reaction to a systemic administration. If the direct meningeal irritation allows a rather easy recognition, the immunologic hypersensitivity reaction is a source of challenging diagnostics. DIAM linked to a systemic treatment exerts typically an early onset, usually within a week. This period can be shortened to a few hours in case of drug rechallenge. The fast and spontaneous regression of clinical symptoms is usual after stopping the suspected drug. Apart from these chronological aspects, no specific clinical or biological parameters are pathognomonic. CSF analysis usually shows pleiocytosis. The proteinorachia is increased while glycorachia remains normal. Underlying pathologies can stimulate the occurrence of DIAM. Thus, systemic lupus erythematosus appears to promote DIAM during NSAID therapy, especially ibuprofen-based one. Similarly, some patients with chronic migraine are prone to intravenous immunoglobulin-induced aseptic meningitis. DIAM will be mainly evoked on chronological criteria such as rapid occurrence after initiation, rapid regression after discontinuation, and recurrence after rechallenge of the suspected drug. When occurring, positive rechallenge may be very useful in the absence of initial diagnosis. Finally, DIAM remains a diagnosis of elimination. It should be suggested only after all infectious causes have been ruled out.

Etiologies and Management of Aseptic Meningitis in Patients Admitted to an Internal Medicine Department.

Several studies have focused on the clinical and biological characteristics of meningitis in order to distinguish between bacterial and viral meningitis in the emergency setting. However, little is known about the etiologies and outcomes of aseptic meningitis in patients admitted to Internal Medicine.The aim of the study is to describe the etiologies, characteristics, and outcomes of aseptic meningitis with or without encephalitis in adults admitted to an Internal Medicine Department.A retrospective cohort study was conducted in the Internal Medicine Department of the Lariboisière Hospital in Paris, France, from January 2009 to December 2011. Clinical and biological characteristics of aseptic meningitis were recorded. These included cerebrospinal fluid analysis, results of polymerase chain reaction testing, final diagnoses, and therapeutic management.The cohort included 180 patients fulfilling the criteria for aseptic meningitis with (n = 56) or without (n = 124) encephalitis. A definitive etiological diagnosis was established in 83 of the 180 cases. Of the cases with a definitive diagnosis, 73 were due to infectious agents, mainly enteroviruses, Herpes Simplex Virus 2, and Varicella Zoster Virus (43.4%, 16.8%, and 14.5% respectively). Inflammatory diseases were diagnosed in 7 cases. Among the 97 cases without definitive diagnoses, 26 (26.8%) remained free of treatment throughout their management whereas antiviral or antibiotic therapy was initiated in the emergency department for the remaining 71 patients. The treatment was discontinued in only 10 patients deemed to have viral meningitis upon admission to Internal Medicine.The prevalence of inflammatory diseases among patients admitted to internal medicine for aseptic meningitis is not rare (4% of overall aseptic meningitis). The PCR upon admission to the emergency department is obviously of major importance for the prompt optimization of therapy and management. However, meningitis due to viral agents or inflammatory diseases could also be distinguished according to several clinical and biological characteristics highlighted in this retrospective study. As recommendations are now available concerning the prescriptions of antiviral agents in viral meningitis, better therapeutic management is expected in the future.

[Benign recurring aseptic meningitis. What requires our attention?]. / Benigne rekurrierende aseptische Meningitis. Worauf muss man achten?

Benign recurrent aseptic meningitis (BRAM) or Mollaret's meningitis is a rare disease characterized by recurrent episodes of aseptic meningitis followed by spontaneous recovery. Disease courses over several years have been reported. In most cases, BRAM is caused by HSV-2, less frequently by other viruses or autoimmune diseases. In up to 10 %, the aetiology remains unclear. We present a case of idiopathic BRAM and discuss clinical findings, diagnosis and therapeutic options of this rare illness.

Parâmetros laboratoriais do líquido cefalorraquidiano em indivíduos com meningite por enterovírus / Laboratory parameters of cerebrospinal fluid in individuals with enterovirus meningitis

A meningite é a principal síndrome infecciosa que afeta o sistema nervoso central, e grande parte dos casos são ocasionados por infecções virais, principalmente por Enterovirus. O diagnóstico clínico para a verificação da etiologia da meningite ainda apresenta grandes desafios. O teste de Reação em Cadeia da Polimerase, leucócitos, hemácias, glicose, proteína e lactato no líquido cefalorraquidiano fornecem os primeiros indícios para o diagnóstico. No entanto, os valores de referência de alguns parâmetros podem sofrer alteraçõesOBJETIVO: Verificar parâmetros laboratoriais do líquido cefalorraquidiano em indivíduos com meningite por Enterovirus e, posteriormente, analisar suas relações por faixa etáriaMÉTODO: Foi realizado um estudo descritivo, com base nos dados do serviço de referência de coleta de líquido cefalorraquiano, localizado em São Paulo, Brasil. Totalizou-se em 202 indivíduos que apresentaram meningite por Enterovirus. Os dados foram analisados pelo teste de Shapiro-Wilk e Kruskal-Wallis (IC = 95%, p < 0,05) e representados pela mediana e percentil 25 e 75...

Meningitis is the leading infectious syndrome that affects the central nervous system, and most cases are caused by viral infections, mainly enterovirus. The clinical diagnosis for meningitis etiology still presents major challenges. The analysis of polymerase chain reaction (PCR), white blood cells, red blood cells, glucose, protein, and lactate in the cerebrospinal fluid (CSF) provides the first clues to the diagnosis. However, the reference values of some parameters can suffer changesOBJECTIVE: Analyze the laboratory parameters of CSF in patients with enterovirus meningitis, and then, theirrelationship by age groupMETHODS: A descriptive study was conducted based on data from a CSF reference service, located in São Paulo, Brazil, on 202 individuals who had enterovirus meningitis. Data was analysed by the Shapiro-Wilk and Kruskal-Wallis tests (CI = 95%, p < 0.05) and represented by the median and percentile 25 and 75, respectively...

Aseptic meningitis occurring during anti-TNF-alpha therapy in rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVES: Aseptic meningitis is a rare and aggressive complication of rheumatoid arthritis (RA), usually histologically characterised by rheumatoid nodules and lymphocytic aggregates in leptomeninges. The aim of this study was to describe the clinical onset and evolution of aseptic meningitis occurring during anti-TNF-alpha (TNF-α) therapy. METHODS: we retrospectively analysed the clinical records of patients with RA or ankylosing apondylitis (AS) treated by TNF-α drugs in the last 10 years. RESULTS: Four out of 718 patients, treated with TNF-α, developed meningitis after a mean of 5 years (SD: 3.7) of TNF-α exposure (0.55%). Three subjects were affected by long-standing RA (median: 11 years, IQR:8.5-25), one patient by active AS of 8 years' duration. RA patients were treated with etanercept (2 cases) and infliximab (1 case), in association with methotrexate and prednisone. The AS patient was treated with adalimumab. Neurological onset was focal epilepsy (3 cases) and dysarthria (1 case). RM showed leptomeningeal enhancement of basal nuclei (1 case) or fronto-parietal zone (3 cases), associated in one patient with cerebritis. Bacterial, viral or parasitic infections were excluded. One patient underwent cerebral biopsy showing T and B lymphocytes' aggregates. All patients discontinued TNF-α drugs and were treated with high dose of steroids, added to methotrexate in two cases. Neurological symptoms resolved without residuals, and meningeal enhancement showed resolution with high latency. CONCLUSIONS: Meningeal inflammation is a rare manifestation occurring in long-standing RA and AS in clinical remission. TNF-α therapy did not prevent this extra-articular complication.

[Aseptic meningitis in an adult population. Etiology and utility of molecular techniques in the clinical management of patients]. / Meningitis aséptica en la población adulta. Etiología y utilidad de las técnicas moleculares en el manejo clínico del paciente.

OBJECTIVE: This study describes the epidemiological, clinical and microbiological features of acute aseptic meningitis (AAM) in an adult population, and evaluates the impact of microbiological results on the clinical management of patients. PATIENTS AND METHODS: Cases of AAM were prospectively collected between 2007 and 2010 among immunocompetent patients over 14 years-old. Enteroviruses and herpes viruses were determined using nucleic acids detection in CSF. Demographic and clinical data were retrospectively collected from medical records. RESULTS: A total of 94 patients were included, of whom 84 were diagnosed with viral meningitis (VM). The annual incidence of VM ranged from 2.4 to 15.3 cases per 100,000 inhabitants. An aetiological diagnosis was obtained in 76.2% of the patients with VM, 55 enterovirus, 4 HSV-2, 3 VZV, one HSV-1, and one EBV. Forty five per cent of patients were admitted to hospital and 65.8% of them received antibiotic treatment. A positive result prompted immediate discharge of 80% of inpatients and discontinuation of antibiotic therapy in 94.1% of them. The median duration of admission to hospital in these patients was 2.8±2.9 days. Patients without available results during admission completed the antibiotic treatment, and the median hospital stay was 11.6±4.6 days. CONCLUSIONS: The annual incidence of AAM is variable. Enteroviruses were the main aetiological agent. Molecular tests revealed the aetiology in 76.2% of cases. Almost half of the patients required hospitalisation, and in these cases a positive result can lead to the immediate discharge of patients, and the diagnostic and therapeutic interventions can be reduced.

[Acute disseminated encephalomyelitis in children as the result of aseptic meningitis - a report of two cases]. / Ostre rozsiane zapalenie mózgu i rdzenia kregowego u dzieci jako nastepstwo jalowego zapalenia opon mózgowo-rdzeniowych - opis dwóch przypadków.

Acute disseminated encephalomyelitis (ADEM) is an inflammation of the spinal cord and brain. Diagnosis of ADEM, due to its rare occurrence and lack of definite laboratory indices, is difficult and is never totally certain. The clinical criterion required for the diagnosis is presence of acute symptoms from the brain and/or spine with fever, occurring after viral or bacterial infection, vaccination or serum administration. Differentiation between ADEM and acute multiple sclerosis in children is difficult, and diagnosis of ADEM may only be confirmed after years of observation, especially as multiple sclerosis is more common than ADEM. The most useful tool in differentiation between the two diseases is MRI. The aim of the study was to present two cases of ADEM with unknown aetiology after aseptic meningitis in children.

Aseptic meningitis in association with glyphosate-surfactant herbicide poisoning.

INTRODUCTION: The mechanisms underlying early central nervous system (CNS) signs and symptoms of glyphosate-surfactant herbicide (GlySH) poisoning are unclear. CASE PRESENTATION: A 58-year-old woman ingested approximately 150 mL of GlySH containing 41% glyphosate and 15% polyoxyethyleneamine. Two days later, she was admitted in the Emergency Center in a semicomatose state. Acute respiratory distress syndrome, circulatory collapse, acute renal failure, and disseminated intravascular coagulopathy were diagnosed. Meningitis was also suspected as she demonstrated Kernig's sign and significant neck stiffness with rigidity of the extremities as well as consciousness disturbance and fever (38.4°C). Investigations of cerebrospinal fluid (CSF) revealed the presence of glyphosate (122.5 µg/mL), significant elevation of IL-6 (394 µg/mL), and pleocytosis (32 cells/µL) with monocyte dominance. All bacteriological and virological tests were later found to be negative. She recovered completely after responding to aggressive supportive care in the intensive care unit. All signs and symptoms suggesting meningitis resolved as the concentration of glyphosate in CSF decreased. She was discharged on day 39 of hospitalization. DISCUSSION: These findings suggest that the present case involved aseptic meningitis in association with GlySH poisoning. CONCLUSION: CNS signs and symptoms induced by aseptic meningitis should be considered in cases of glyphosate-surfactant herbicide poisoning.