Recurrent disseminated coccidioidal meningitis in two subsequent pregnancies.

OBJECTIVE: Recurrent disseminated coccidioidal meningitis in two subsequent pregnancies is rare and can pose a challenge in ensuring the health of both mother and baby. In this unique case we highlight this rare occurrence and subsequent treatment. CASE REPORT: A 29-year-old G4P1021 with a history of disseminated coccidioidomycosis in a previous pregnancy presented at 8 weeks gestation with nausea, headache, and neck pain. Cerebrospinal fluid analysis was positive for recurrent coccidioidal infection. She was started on Amphotericin and discharged. She re-presented at 30 week's gestation with phonophobia and photophobia, emesis, neck pain and swelling. MRI showed evidence of ventriculomegaly with communicating hydrocephalus. She was treated with therapeutic lumbar punctures throughout her pregnancy and a ventriculoperitoneal shunt following delivery. She had a spontaneous vaginal delivery at 38 weeks and 3 days with no complications. CONCLUSION: This unique case highlights the susceptibility of recurrent disseminated coccidioidomycosis in subsequent pregnancies and treatment thereof.

Cerebral vasospasm due to Fusarium solani meningitis: A complication from medical tourism. Case report and literature review.

OBJECTIVES: Medical tourism is expanding globally, with patients seeking cosmetic procedures abroad. To date, little information is known regarding the risks and outcomes of cosmetic tourism, especially potential stroke complications. Here, we present a case of fungal meningitis in the setting of medical tourism leading to ischemic strokes and vasospasm. MATERIAL AND METHODS: We describe an immunocompetent 29-year-old female patient who initially presented with intractable headaches and an abnormal cerebrospinal fluid (CSF) profile who was eventually diagnosed with Fusarium solani meningitis as a part of a common source outbreak in Matamoros, Mexico. These patients were part of a cohort who underwent cosmetic procedures requiring spinal anesthesia. This report also highlights the unusual clinical course leading to poor outcomes in such conditions. RESULTS: The patient initially presented with headaches, papilledema, elevated opening pressure on the spinal tap, abnormal CSF studies, and eventually developed ischemic strokes and hydrocephalus. CSF showed positive beta D-Glucan with repeated negative CSF fungal cultures. A cerebral angiogram revealed extensive basilar artery vasospasm that led to ischemic strokes. Continued clinical worsening and lack of response to antifungal treatment prompted further imaging that revealed significant non-obstructive hydrocephalus subsequently complicated by spontaneous intracranial hemorrhage. CSF PCR for Fusarium solani species was positive days after her passing. CONCLUSION: This novel case highlights fungal meningitis caused by Fusarium solani complicated by bilateral ischemic strokes stemming from basilar artery vasospasm. Complications from medical tourism impact not only individual patients but also the health systems of both countries. Professional and regulatory entities for cosmetic surgeries must highlight and educate patients on the risks and complications of cosmetic surgeries happening abroad. Physicians should be aware of ongoing outbreaks and possible complications of these procedures.

Cerebrovascular Complications Associated With Iatrogenic Fungal Meningitis Following Surgical Procedures in Mexico.

BACKGROUND: The current fungal meningitis outbreak caused by contaminated epidural anesthesia with Fusarium solani among patients who underwent surgical procedures in Matamoros, Mexico remains a cause of concern. Its association with an increased susceptibility for cerebrovascular complications (CVC) has not been reported. This single-center study describes 3 patients with a unique pattern of CVC attributed to fungal meningitis. METHODS: A retrospective case series of patients diagnosed with fungal meningitis following surgical procedures under contaminated epidural anesthesia who developed a unique pattern of CVC during their hospitalization. RESULTS: Three female patients (mean age, 35 years) with CVC due to iatrogenic fungal meningitis were included. Positive Fungitell ß-D-glucan assay in cerebrospinal fluid was documented in all cases, and F. solani was confirmed by polymerase chain reaction in case 3. All cases were complicated by severe vertebrobasilar circulation vasculopathy and arterial dissections with resultant subarachnoid hemorrhage and intraventricular hemorrhage, ultimately leading to patients' death. CONCLUSIONS: The death toll from the ongoing fungal meningitis outbreak keeps rising, underscoring the need for early recognition and aggressive treatment. We highlight the risk for vertebrobasilar circulation CVC among these patients. The angioinvasive nature of F. solani is yet to be clarified; however, a clear pattern has been observed. Public health awareness should be raised and a strong response should be pursued.

Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis.

Disseminated coccidioidomycosis is associated with significant morbidity and mortality. Involvement of the meninges is often fatal if untreated, typically requiring lifelong antifungal therapy and neurosurgical intervention. We present the case of a young male without any known immunocompromising conditions who opted exclusively for medical management of newly diagnosed coccidioidomycosis meningitis with communicating hydrocephalus and discuss the controversy associated with this approach. This case highlights the importance of shared decision-making between patient and clinician, even if the plan diverges from available guidelines. Furthermore, we discuss clinical considerations in approaching the close outpatient monitoring of patients with central nervous system coccidioidomycosis with hydrocephalus.

Asymptomatic Coccidioidal Meningitis Relapse: A Demon in Disguise.

Coccidioides spp is a soil-dwelling, dimorphic fungus that causes coccidioidomycosis. It is endemic to the western hemisphere. Although primarily a respiratory disease, it can also cause a myriad of clinical manifestations, from asymptomatic disease to meningitis. In fact, Coccidioides species is probably the most common etiologic agent of long-term meningitis in California and Arizona. Early diagnosis and treatment are critical to avoid fatal complications. With treatment, the cerebral spinal fluid analysis may return to normal. Relapse of coccidioidal meningitis is usually suspected with recurrence of meningitis symptoms. The patient is a 53-year-old man with a 2-decade history of coccidioidal meningitis who was diagnosed with an asymptomatic relapse of coccidioidal meningitis.

Controversies in the Management of Central Nervous System Coccidioidomycosis.

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

Detection of Coccidioides posadasii in a patient with meningitis using metagenomic next-generation sequencing: a case report.

BACKGROUND: Coccidioidomycosis is a systemic infection caused by dimorphic fungi Coccidioides spp. endemic to Southwestern United States and Central and South America. A history of residence and travel in these areas is essential for the diagnostic of coccidioidomycosis, which has highly variable symptoms ranging from asymptomatic to severe, disseminated infection, and even death. Immunocompromised patients of coccidioidomycosis experience a high risk of dissemination, chronic infection, and mortality. Meningitis is one of the most deleterious coccidioidomycosis and can cause various life-threatening complications. CASE PRESENTATION: Here we report a case of Coccidioides posadasii meningitis in a 49-year-old female who returned to China after one and a half years residence in Los Angeles, USA. The repeated routine cultures using CSF for bacteria or fungi were all negative. To hunt for an infectious etiology, the state-of-the-art technology metagenomic next-generation sequencing (mNGS) was then utilized, suggesting Coccidioides posadasii. Organizational pathological examination and polymerase-chain-reaction (PCR) results subsequently confirmed the mNGS detection. CONCLUSION: To our knowledge, cases for coccidioidal meningitis have been rarely reported in China. While global travelling may spread this disease across continents and make the diagnosis more difficult. mNGS can detect almost all known pathogens with high sensitivity and specificity, especially for uncommon pathogen, such as Coccidioides posadasii in China.

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab.

BACKGROUND: Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. CASE PRESENTATION: We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. CONCLUSIONS: Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

First case report of fungal meningitis due to a polypore mushroom Irpex lacteus.

A 73-year-old Japanese man with a medical history of sarcoidosis was diagnosed with meningitis caused by an undetermined fungus. For further identification, the cerebrospinal fluid sample was analyzed for the rDNA internally transcribed spacer regions, and the fungus was identified as Irpex lacteus. I. lacteus is classified under phylum Basidiomycota and is a wood-rotting bracket mushroom. Although there is no standard treatment regimen for I. lacteus infections, amphotericin B was effective in this patient. Herein, we present, to our knowledge, the first reported case of fungal meningitis caused by I. lacteus, its treatment course, and review relevant published literature.

Central nervous system aspergillosis in immunocompetent patients: Case series and literature review.

The aim of this study was to investigate the clinical characteristics of central nervous system (CNS) aspergillosis in immunocompetent patients.This study enrolled six immunocompetent patients diagnosed with CNS aspergillosis. Additionally, we reviewed the clinical profiles for 28 cases reported in the literature. The age, gender, etiology of Aspergillus infection, clinical manifestations, location of the lesion, treatment, and prognosis were analyzed.There were 19 men (average age, 54.6 ±â€Š14.3 years) and 15 women (average age, 47.0 ±â€Š19.4 years). The clinical manifestations included headache (55.9%; n = 19), visual impairment (32.4%; n = 11), diplopia (32.4%; n = 11), hemiplegia (20.6%; n = 7), fever (17.6%; n = 6), and epilepsy (8.8%; n = 3). According to the radiological features, CNS aspergillosis lesions were divided into two subtypes: parenchymal lesions in the cerebral lobes (n = 11), and meningeal lesions in the meninges (n = 23). The patients with meningeal lesions are easy to be complicated with more serious cerebrovascular diseases, such as subarachnoid hemorrhage and massive infarction. Most of the lesions in brain parenchyma were abscess formation, and magnetic resonance imaging showed ring enhancement. The clinical diagnosis of Aspergillus infection was mainly based on brain biopsy (n = 14), autopsy (n = 8), pathological examination of adjacent brain tissues (n = 7), cerebrospinal fluid (CSF) or tissue culture (n = 3), and second-generation sequencing analysis of the CSF (n = 3). Clinical improvement was achieved in 23 cases, and 11 patients succumbed to the disease. Voriconazole treatment was effective in 24 (70.6%) cases.Immunocompetent subjects are also at risk for Aspergillus infections. Concomitant cerebrovascular diseases are common in patients with CNS aspergillosis, especially in patients with meningeal aspergillosis. Parenchymal aspergillosis lesions are usually localized and manifest as brain abscesses with annular enhancement on magnetic resonance imaging. Biopsy, CSF culture, and next-generation sequencing are mainstream diagnostic modalities. Voriconazole is an effective treatment for Aspergillus infection, and early diagnosis and treatment should be highlighted.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Case Report: Chronic Fungal Meningitis Masquerading as Tubercular Meningitis.

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of Fonsecaea pedrosoi, which is classically known to cause brain abscesses. Here, we report the diagnostic odyssey in a patient with chronic meningitis from a region endemic for tuberculosis and describe the challenges in establishing the accurate diagnosis. Lack of therapeutic response to an adequate trial of empirical antitubercular therapy warrants search for alternative causes, including fungal meningitis. We highlight the uncommon manifestation of F. pedrosoi with chronic meningitis as well as the protracted clinical course despite not receiving antifungal therapy.

Aspergillus fumigatus meningitis in an immunocompetent young woman.

Aspergillus meningitis is a rare clinical entity that is much more frequently observed among immunocompetent patients. Here we present the case of a 28 year old immunocompetent lady with Aspergillus fumigatus meningitis possibly following spinal anaesthesia for her caesarean section. The diagnosis of Aspergillus meningitis is very difficult and challenging. Even after diagnosis, clinical outcomes remain poor with treatment. We wish to highlight the need for high index of suspicion for Fungal meningitis in patients presenting with meningism after Neurosurgeries and procedures involving invasion into the CSF compartment.

Sporotrichosis in renal transplant patients: two case reports and a review of the literature.

INTRODUCTION: Sporotrichosis is a rare fungal infection in transplant patients; among these patients, it occurs mostly in renal transplant patients. Sporothrix schenkii is the primary pathogen responsible. A high index of suspicion is required to make the diagnosis keeping important differential diagnoses in mind. History of trauma through recreational or occupational exposure to the fungus may assist in making the diagnosis. Treatment is difficult, with long-term use of potentially nephrotoxic and cytochrome P450 inhibitor antifungal agents leading to potential calcineurin inhibitors toxicity. We describe two renal transplant patients presenting with distinct sporotrichosis infection: "Case 2" being only the second reported case ever of meningeal sporotrichosis. We subsequently review the general aspects of sporotrichosis, specifically in renal transplant patients as described in the medical literature. CASE PRESENTATION: Case 1, a 43-year-old mixed ancestry male patient presented with a non-healing ulcer on the left arm for 1 year, he was diagnosed with cutaneous sporotrichosis and was successfully treated with itraconazole monotherapy. Case 2, a 56-year-old mixed ancestry male patient presented with a slow decline in functions, confusion, inappropriate behavior, rigors and significant loss of weight and appetite over the past 4 months, he was diagnosed with meningeal sporotrichosis and was successfully treated with a combination of deoxycholate amphotericin B and itraconazole. CONCLUSION: Physicians taking care of renal transplant patients should have a high index of suspicion for sporotrichosis infection particularly when conventional therapy for common conditions fails. Susceptibility testing is recommended to identify the most effective antifungal agent and its dose. The slow nature of growth of Sporothrix schenkii necessitates patients to be on amphotericin B until the time results are available. Finally, there is a need to be aware of potential drug-drug interactions of the azoles with calcineurin inhibitors and the required dose adjustments to prevent therapy related adverse events.

Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients.

Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS. Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively. Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442.

Aspergillus meningitis in a patient with chronic lymphocytic leukemia.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis.

Efficacy of Cerebrospinal Fluid Beta-d-Glucan Diagnostic Testing for Fungal Meningitis: a Systematic Review.

Several case reports and cohort studies have examined the use of (1,3)-beta-d-glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta-d-glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta-d-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded. A total of 939 records were examined via a PubMed search. One hundred eighteen records remained after duplicates were removed, and 104 records were excluded, as they did not examine cerebrospinal fluid, included animals, or focused on nonfungal infections. Fourteen studies were included in this systematic review. A variety of fungi, including species of Candida, Aspergillus, Exserohilum, Cryptococcus, Histoplasma, and Coccidioides, were studied, although most were case reports. Diagnostic accuracy was examined in 5 studies. Cerebrospinal fluid (CSF) (1,3)-beta-d-glucan measurement showed >95% sensitivity in the corticosteroid injection-related outbreak of Exserohilum rostratum One study in Histoplasma meningitis found 53% (53/87) sensitivity and 87% (133/153) specificity, while another study of Cryptococcus meningitis found 89% (69/78) sensitivity and 85% (33/39) specificity. CSF (1,3)-beta-d-glucan testing may be useful, primarily as a nonspecific marker of fungal meningitis. Although the FDA black box warning states that Cryptococcus spp. do not make (1,3)-beta-d-glucan, the current evidence shows that (1,3)-beta-d-glucan is detectable in cryptococcal meningitis. Organism-specific testing should be used in conjunction with (1,3)-beta-d-glucan measurement.