Meningitis in Children: Still a Can't-Miss Diagnosis.

Although vaccination and antimicrobial treatment have significantly impacted the frequency and outcomes of meningitis in children, meningitis remains a critical can't-miss diagnosis for children, where early recognition and appropriate treatment can improve survival and neurologic outcomes. Signs and symptoms may be nonspecific, particularly in infants, and require a high index of suspicion to recognize potential meningitis and obtain the cerebrospinal fluid studies necessary for diagnosis. Understanding the pathogens associated with each age group and specific risk factors informs optimal empirical antimicrobial therapy. Early treatment and developmental support can significantly improve the survival rates and lifelong neurodevelopment of children with central nervous system infections.

Dural and Leptomeningeal Diseases: Anatomy, Causes, and Neuroimaging Findings.

Meningeal lesions can be caused by various conditions and pose diagnostic challenges. The authors review the anatomy of the meninges in the brain and spinal cord to provide a better understanding of the localization and extension of these diseases and summarize the clinical and imaging features of various conditions that cause dural and/or leptomeningeal enhancing lesions. These conditions include infectious meningitis (bacterial, tuberculous, viral, and fungal), autoimmune diseases (vasculitis, connective tissue diseases, autoimmune meningoencephalitis, Vogt-Koyanagi-Harada disease, neuro-Behçet syndrome, Susac syndrome, and sarcoidosis), primary and secondary tumors (meningioma, diffuse leptomeningeal glioneuronal tumor, melanocytic tumors, and lymphoma), tumorlike diseases (histiocytosis and immunoglobulin G4-related diseases), medication-induced diseases (immune-related adverse effects and posterior reversible encephalopathy syndrome), and other conditions (spontaneous intracranial hypotension, amyloidosis, and moyamoya disease). Although meningeal lesions may manifest with nonspecific imaging findings, correct diagnosis is important because the treatment strategy varies among these diseases. ©RSNA, 2023 Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

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.

Critical care management of meningitis and encephalitis: an update.

PURPOSE OF REVIEW: Meningitis and encephalitis represent severe neurological syndromes associated with encephalopathy, seizures, focal deficits, and neurological sequelae in survivors. We update on the critical care management of adult patients with severe meningitis and encephalitis. RECENT FINDINGS: Large multicenter studies conducted in the adult population improved current knowledge on the epidemiology and outcomes of patients with severe meningitis and encephalitis. An early multimodal diagnostic workup (including CSF analysis, brain MRI, EEG, and serum studies) is mandatory for diagnosis and prognostication in those patients.New diagnostic methods, including multiplex PCR and next-generation sequencing techniques, allow for a faster differential diagnosis of infectious causes that may require specific antimicrobial therapy. Autoimmune causes of encephalitis, which may require urgent immunotherapy, are also increasingly recognized in the ICU setting. Although observational data suggest that early combined immunotherapy is associated with better neurological outcomes in patients with autoimmune encephalitis, randomized clinical trials have yet to be performed. SUMMARY: Our review highlights the importance of an early multimodal approach for diagnosing severe meningitis and encephalitis. Randomized clinical trials are needed to identify pharmacological interventions that may improve patients' outcomes.

Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

An uncommon cause of sepsis following dog exposure.

ABSTRACT: Capnocytophaga canimorsus is a bacteria commonly found in the normal oral cavity of dogs that can cause bacteremia in immunocompromised patients following a dog bite. This case describes sepsis and disseminated intravascular coagulation associated with C. canimorsus in a patient with a history of alcohol abuse. Clinicians must be alert to the risk factors for this infection and provide appropriate prophylaxis following dog bites.

Efficacy of rituximab for anti-neutrophil cytoplasmic antibody-associated hypertrophic pachymeningitis: a case series.

OBJECTIVES: This study researched the efficacy of rituximab (RTX) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated hypertrophic pachymeningitis (HP). METHODS: Eight patients were identified by retrospective chart review from local registries at four hospitals in Japan. All patients met the Chapel Hill 2012 Consensus Conference definitions of ANCA-associated vasculitis and had disease complicated with HP. We assessed the dose of glucocorticoids, C-reactive protein (CRP) levels, Birmingham vasculitis activity score (BVAS) and contrast-enhanced magnetic resonance imaging (MRI) findings of HP before and after RTX administration. RESULTS: Three of eight patients were female. The median age was 68 years. No patients had HP at onset of vasculitis. Two patients had a relapse of HP before RTX administration. RTX was used as the initial treatment for HP in three patient. The daily dose of glucocorticoids, CRP levels and BVAS decreased from baseline to 6 months after RTX treatment in all patients. Evaluation of HP by contrast-enhanced MRI showed improvement in seven of eight cases. All of seven patients achieved sustained remission at 6 months after RTX treatment. No serious adverse events were observed in any patient. CONCLUSIONS: Our case series highlights the efficacy of RTX in patients with difficult-to-treat ANCA-associated HP. Future prospective studies are warranted to establish B-cell depletion therapy by RTX as a treatment option for ANCA-associated HP.

An Update on Idiopathic Hypertrophic Cranial Pachymeningitis for the Headache Practitioner.

PURPOSE OF REVIEW: We aim to review idiopathic hypertrophic cranial pachymeninigitis (IHCP), describe common head pain patterns and features associated with the disorder, suggest potential classification of head pain syndromes based on the recently published International Classification of Headache Disorders-3, explore pathophysiology found to be associated with cases of IHCP, and indicate common treatment for the disorder. RECENT FINDINGS: It is suggested that a subset of IHCP is an IgG4-related autoimmune disorder. Patients with IHCP were found to have elevated cerebrospinal fluid (CSF) protein and lymphocytic pleocytosis. Corticosteroids are a mainstay of treatment. Other immunosuppressive agents and steroid sparing agents as add-on therapy may have utility in the treatment of cases refractory to corticosteroids alone. Clinical manifestations of IHCP depend upon the location of the inflammatory lesions and compression of the adjacent nervous system structures. Headache and loss of cranial nerve function were the most common presenting features of hypertrophic cranial pachymeninigitis. Several headache diagnoses may result from IHCP. Gadolinium-enhanced MRI is the standard imaging modality for diagnosing. Although the pathophysiology is poorly understood, many cases of hypertrophic pachymeninigitis (HP) are thought to be closely related to inflammatory disorders. Cases of HP previously thought to be idiopathic may have IgG4 pathophysiology. CSF and serological studies are helpful. Treatment involves immunosuppressive agents. Advancement in neuroimaging, assays, tests, and further delineation of inflammatory disorders affecting the nervous system may provide further insight to the etiology of cases of HP previously considered and diagnosed as idiopathic.

Clinical Performance Measures for Neurocritical Care: A Statement for Healthcare Professionals from the Neurocritical Care Society.

BACKGROUND: Performance measures are tools to measure the quality of clinical care. To date, there is no organized set of performance measures for neurocritical care. METHODS: The Neurocritical Care Society convened a multidisciplinary writing committee to develop performance measures relevant to neurocritical care delivery in the inpatient setting. A formal methodology was used that included systematic review of the medical literature for 13 major neurocritical care conditions, extraction of high-level recommendations from clinical practice guidelines, and development of a measurement specification form. RESULTS: A total of 50,257 citations were reviewed of which 150 contained strong recommendations deemed suitable for consideration as neurocritical care performance measures. Twenty-one measures were developed across nine different conditions and two neurocritical care processes of care. CONCLUSIONS: This is the first organized Neurocritical Care Performance Measure Set. Next steps should focus on field testing to refine measure criteria and assess implementation.

Meningitis and encephalitis management in the ICU.

PURPOSE OF REVIEW: Management of patients with meningitis and encephalitis oftentimes requires ICU level of care. This article is an update on management for meningitis and encephalitis with focus on clinical care in the ICU. Information provided is based on a review of recent studies with focus on studies since 2017. RECENT FINDINGS: Advances in diagnostic and treatment approach for different pathogens are presented. Nosocomial meningitis now constitutes a major part of brain infections seen in ICUs in the developed world. Advances in ICU care of central nervous system (CNS) infections include application of newer diagnostic methods, improved understanding and delivery of antibiotics to the CNS, infection prevention for nosocomial infections, and application of neuromonitoring where indicated. SUMMARY: Advances in diagnostics and therapeutic approach to CNS infections are continually made. For intensivists, focus on neuromonitoring and brain resuscitation in critically ill patients with CNS infections may present a path to enhance preservation of brain function and improve outcomes. VIDEO ABSTRACT: http://links.lww.com/COCC/A22.

Outcomes measures in children after acute central nervous system infections and malaria.

PURPOSE OF REVIEW: Acute central nervous system (CNS) infections in children result in significant mortality and neurologic morbidity worldwide. This article summarizes the recent pediatric literature published on outcomes measures used after acute infectious meningitis, encephalitis, and cerebral malaria, and highlights ongoing research efforts to standardize outcomes measurements. Search terms were geared toward functional, cognitive, behavioral, and other outcome assessments. RECENT FINDINGS: Recent data suggest that, depending on microbiological cause, there are differences in currently used outcome measures following acute CNS infections. Outcomes assessments include a variety of formal psychological tests (structured interviews and neuropsychological tests of cognitive and motor functioning) and dichotomized or ordinal scales. Standardization of outcome measures, however, is lacking. Global efforts to standardize outcomes that encompass both the child and family are ongoing. SUMMARY: Centers worldwide can track and measure a variety of cognitive, behavioral, and functional outcomes after acute CNS infections. Standardized documentation and coding of clinically important outcomes is needed. Further research to evaluate effective practices using acute adjunctive and rehabilitation therapies will be aided by outcome measure standardization.

Seminoma with Neoplastic Meningitis Treated with Craniospinal Irradiation.

Pure seminoma is a histological subtype of testicular cancer that accounts for 50% of testicular germ cell tumors. It has a very low rate of metastasis to the central nervous system, with only one previously reported case of neoplastic meningitis (cancer that has spread to the cerebrospinal fluid). Traditionally, neoplastic meningitis has an ominous prognosis when associated with primary tumors that commonly spread to the leptomeninges, like breast and lung. This article highlights a unique case of pure seminoma with neoplastic meningitis and illustrates the effectiveness of craniospinal irradiation as a treatment modality.

Outcomes in Patients With Severe West Nile Neuroinvasive Disease.

OBJECTIVE: To assess the long-term outcomes of patients hospitalized with severe West Nile neuroinvasive disease. DESIGN: Retrospective cohort. SETTING: Patients admitted to a referral center (Saint Mary's Hospital, Mayo Clinic). PARTICIPANTS: Twenty-six patients with West Nile neuroinvasive disease were identified by retrospective search of electronic database of Saint Mary's Hospital from January 1999 to November 2016. INTERVENTIONS: Retrospective electronic medical records review and prospective telephone follow-up. MEASUREMENTS AND MAIN RESULTS: Functional disability and cognitive outcomes were evaluated with the modified Rankin Scale and the Telephone Interview for Cognitive Status scores. Data on the time that the patient returned home after the hospitalization for West Nile neuroinvasive disease and the time of return to work were also collected. We identified 26 patients (81% males), 59 ± 17 years old. After a median hospital stay of 14.5 days (3-126), four patients died and 90% of survivors had a modified Rankin Scale of 3-5. Two additional patients died, and 80% of survivors had a modified Rankin Scale of 0-2 after a median follow-up of 73 months (1-144). Seven patients had cognitive impairment, which was severe in two of them. The combination of encephalitis and acute flaccid paralysis at presentation was associated with lower likelihood of returning home within 1 month after discharge (p < 0.01). Patients who required mechanical ventilation were more likely to have a modified Rankin Scale of 3-5 at last follow-up (p = 0.03), less likely to return home within 1 month of discharge (p < 0.01), less likely to return to their jobs (p < 0.01), and showed a trend toward having cognitive impairment (p = 0.05). CONCLUSIONS: Despite having poor outcomes at discharge, most West Nile neuroinvasive disease survivors with severe early disability can recover functional independence in the long term, justifying aggressive support during the acute phase and extensive rehabilitation efforts.

Infection, Immunodeficiency, and Inflammatory Diseases in Autoimmune Neurology.

When patients present with neurological syndromes, such as encephalopathy/encephalitis, meningitis, and/or myelopathy/myelitis, the differential diagnosis is often broad, including infectious, inflammatory, autoimmune, vascular, and neoplastic etiologies. Just with inflammatory and autoimmune etiologies alone, there are numerous causative diseases. A comprehensive history and physical examination investigating for extraneurologic manifestations of immune-mediated disease is often necessary. Moreover, evaluating for an underlying infection and/or immunodeficiency becomes a critical aspect to the workup. This article will focus on the association of viral infections and dysregulation of the immune system as triggers of autoimmunity, in addition to various systemic inflammatory diseases that can cause neurological disease either with or without an established rheumatological disorder.

Diagnosis and Management of Leukemic and Lymphomatous Meningitis.

BACKGROUND: Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia. METHODS: The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of leukemic and lymphomatous meningitis. RESULTS: Treatment for secondary leukemic and lymphomatous meningitis remains unsatisfactory, and efforts should be made to prevent and treat subclinical disease. Intrathecal and systemic chemotherapy remain the main therapeutic approaches for this disease. Outcomes have improved in patients with primary CNS lymphoma and meningeal involvement. CONCLUSIONS: Appropriate selection of patients at high risk for leukemic and lymphomatous meningitis is important so that preventive strategies can decrease the incidence of this complication of leukemia and lymphoma. Use of chemotherapy agents that cross the blood-brain barrier and the adoption of high-dose chemotherapy with autologous hematopoietic stem cell transplantation have increased the proportion of patients whose primary disease is cured.

Neoplastic Meningitis Due to Lung, Breast, and Melanoma Metastases.

BACKGROUND: Neoplastic meningitis, a central nervous system (CNS) complication of cancer metastatic to the meninges and cerebrospinal fluid (CSF), is relevant to oncologists due to the impact of the disease on patient quality of life and survival rates. METHODS: A review of the literature of articles published in English was conducted with regard to neoplastic meningitis. RESULTS: The incidence of neoplastic meningitis is increasing because patients with cancer are surviving longer in part because of the use of novel therapies with poor CNS penetration. Up to 5% of patients with solid tumors develop neoplastic meningitis during the disease course (breast cancer, lung cancer, and melanoma being the predominantly causative cancers). The rate of median survival in patients with untreated neoplastic meningitis is 1 to 2 months, although it can be as long as 5 months in some cases. Therapeutic options for the treatment of neoplastic meningitis include systemic therapy (cancer-specific, CNS-penetrating chemotherapy or targeted therapies), intra-CSF administration of chemotherapy (methotrexate, cytarabine, thiotepa) and CNS site-specific radiotherapy. Determining whom to treat with neoplastic meningitis remains challenging and, in part, relates to the extent of systemic disease, the neurological burden of disease, the available systemic therapies, and estimated rates of survival. CONCLUSIONS: The prognosis of neoplastic meningitis remains poor. The increasing use of novel, targeted therapies and immunotherapy in solid tumors and its impact on neoplastic meningitis remains to be determined and is an area of active research. Thus, well conducted trials are needed.

Cerebrospinal Fluid Dissemination and Neoplastic Meningitis in Primary Brain Tumors.

BACKGROUND: Neoplastic meningitis, also known as leptomeningeal disease, affects the entire neuraxis. The clinical manifestations of the disease may affect the cranial nerves, cerebral hemispheres, or the spine. Because of the extent of disease involvement, treatment options and disease staging should involve all compartments of the cerebrospinal fluid (CSF) and subarachnoid space. Few studies of patients with primary brain tumors have specifically addressed treatment for the secondary complication of neoplastic meningitis. Therapy for neoplastic meningitis is palliative in nature and, rarely, may have a curative intent. METHODS: A review of the medical literature pertinent to neoplastic meningitis in primary brain tumors was performed. The complication of neoplastic meningitis is described in detail for the various types of primary brain tumors. RESULTS: Treatment of neoplastic meningitis is complicated because determining who should receive aggressive, central nervous system (CNS)-directed therapy is difficult. In general, the therapeutic response of neoplastic meningitis is a function of CSF cytology and, secondarily, of the clinical improvement in neurological manifestations related to the disease. CSF cytology may manifest a rostrocaudal disassociation; thus, consecutive, negative findings require that both lumbar and ventricular cytological testing are performed to confirm the complete response. Based on data from several prospective, randomized trials extrapolated to primary brain tumors, the median rate of survival for neoplastic meningitis is several months. Oftentimes, therapy directed at palliation may improve quality of life by protecting patients from experiencing continued neurological deterioration. CONCLUSIONS: Neoplastic meningitis is a complicated disease in which response to therapy varies by histology. Thus, survival rates after CNS-directed therapy will differ by the underlying primary tumor. Optimal therapy of neoplastic meningitis is poorly defined, and few guidelines exist to guide clinicians on the most appropriate choice of therapy.

Recurrent Meningitis.

PURPOSE OF REVIEW: Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis. RECENT FINDINGS: New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis. Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

Emergency Neurologic Life Support: Meningitis and Encephalitis.

Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis, are severe neurological infections that, if not treated promptly and effectively, lead to poor neurological outcome or death. Because of the value of early recognition and treatment, meningitis and encephalitis was chosen as an Emergency Neurological Life Support protocol. This protocol provides a practical approach to recognition and urgent treatment of bacterial meningitis and encephalitis. Appropriate imaging, spinal fluid analysis, and early empiric treatment are discussed. Though uncommon in its full form, the typical clinical triad of headache, fever, and neck stiffness should alert the clinical practitioner to the possibility of a central nervous system infection. Early attention to the airway and maintaining normotension are crucial steps in the treatment of these patients, as is rapid treatment with anti-infectives and, in some cases, corticosteroids.

A study on the clinical outcomes and management of meningitis at a tertiary care centre.

BACKGROUND: Meningitis is a life threatening central nervous system infection that is prevalent worldwide. Many studies have been conducted on bacterial meningitis, but the information is inadequate on the other types of meningitis, especially prevalent in India. Regional information regarding trends, in terms of etiology and microbiological susceptibility, are essential for timely and adequate management of meningitis. AIMS: The present study was undertaken to evaluate the changing epidemiology of meningitis by reviewing the causative agents, the available laboratory methods for making the etiological diagnosis, the risk factors and the clinical outcomes, and the management of meningitis in our patient population. MATERIALS AND METHODS: It is an observational study conducted at a tertiary care centre. A structured data form was designed to collect the information from the medical records and charts of medical investigations of the patients. Details regarding etiological agents, prevalence of clinical features and management were recorded and interpreted. RESULTS: A total of 147 patients suspected to be having meningitis were included. The common types of meningitis in our study were aseptic (39%), tuberculous (28%), pyogenic (28%), fungal (3%) and others (2%). The classical triad of headache with fever, neck stiffness, and altered mental sensorium was seen in 26% patients, and 83% had at least 2 out of these 4 symptoms. The incidence of seizures was found to be 63% in the presence of aseptic meningitis. Significant clinical improvement was seen in 89% of the patients suffering from aseptic meningitis. CONCLUSIONS: Aseptic meningitis was found to be the predominant type among all different varieties of meningitis. An increased incidence of meningitis was seen in patients with diabetes mellitus. The incidence of seizures was high in viral/aseptic meningitis. The empirical treatment given in most of the cases was ceftriaxone. Isolation of the culpable organisms was possible in a very few cases due to the usage of empirical antibiotics prior to the performance of the lumbar puncture for the diagnostic analysis of the cerebrospinal fluid.