Rhinocerebral Zygomycosis Due to a Lichtheimia ramosa Infection in a Calf: Neural Spread Through the Olfactory Nerves.

Here, we report a case of rhinocerebral zygomycosis due to a Lichtheimia ramosa infection in a calf. A histopathological examination revealed that a fungus had invaded the brain through the olfactory nerves. Lichtheimia ramosa was detected by polymerase chain reaction analysis of DNA extracted from formalin-fixed paraffin-embedded samples of the affected tissue. This is the first case of rhinocerebral zygomycosis to involve cattle. Also, this is the first such case to involve fungal invasion into the central nervous system through the cranial nerve itself, rather than through perineural tissue.

Multiple Intracranial Aneurysms from Coccidioidal Meningitis: Case Report Featuring Aneurysm Formation and Spontaneous Thrombosis with Literature Review.

BACKGROUND: Coccidioidal meningitis can progress to vasculitis with aneurysm formation. Although aneurysmogenesis is rare, it carries exceptionally high mortality. Except in one instance, prior case reports have documented universally fatal consequences. CASE DESCRIPTION: A 26-year-old man developed disseminated coccidioidomycosis with formation of multiple aneurysms throughout the anterior intracranial vasculature bilaterally. This report is unique in that it chronicles the formation and subsequent spontaneous thrombosis of several aneurysms over a 4-week period. In total 10 aneurysms were documented in the same patient-the highest reported to date. The patient was eventually discharged from the hospital for what has heretofore been a universally fatal disease process. Neurologic examination and vascular imaging 1 month after discharge demonstrated stable findings. CONCLUSIONS: Coccidioidal aneurysms carry a high mortality. The mainstay of therapy remains lifelong triazole antifungal therapy with the addition of liposomal amphotericin in cases of treatment failure. Steroid use is controversial but should be considered whenever there is vascular involvement. Although watchful waiting is reasonable in light of the possibility of spontaneous thrombosis with medical management, dynamic changes in aneurysm size or configuration should prompt timely endovascular or operative interventions.

Aspergillus sinusitis complicated with meningitis and multiple cerebral infarctions in immunocompetent patient.

This is a case of a 33-year-old male complaining of severe headache, neck pain, photophobia, vomiting and high-grade fever of several days. He had history of nasal polyp removal and recurrent sinusitis in the last 8 years. On examination: conscious with glasco coma scale (GCS) 15/15 and normal limbs strength but with positive Babinski sign. For further observation, he was admitted and full work-up was done. Even though full empirical antibiotics were started, there was no immediate improvement and he deteriorated dramatically developing ocular deficit, hydrocephalus and lower level of consciousness with multiple infarctions found at different areas in brain. After that point, a decompressive craniectomy was done, and multiple antibiotics and antifungal medications were prescribed. However, he deteriorated to GCS 3/15; cardiopulmonary resuscitations were not successful, as he demised next day. It shall be noted that aspergillosis can lead to difficult complications, so diagnosis and treatments should not be delayed.

Candida Meningitis After Transsphenoidal Surgery: A Single-Institution Case Series and Literature Review.

Candida meningitis after neurosurgical procedures is a rare but potentially devastating complication. The presentation of meningitis can be insidious in immunosuppressed patients and thus can be easily overlooked. Cerebrospinal fluid studies often resemble bacterial profiles, and cultures can be falsely negative. Candida albicans is the most common species identified in postsurgical Candida meningitis, and delay in diagnosis and treatment can be devastating. The standard induction therapy for Candida meningitis has been amphotericin B combined with flucytosine. A high index of suspicion is needed in any patient with risk factors such as abdominal surgery, bowel perforation, recent broad spectrum antibiotic therapy, intravenous drug use, extremes of age, indwelling catheters, and immunosuppression such as AIDS, malignancy, antineoplastic therapy, and steroid use. Here, we describe 3 case presentations of patients with giant skull base tumors who developed postsurgical Candida meningitis, each with vastly different clinical courses and outcomes, ranging from benign to catastrophic. We performed a literature review with special focus on common risk factors, Candida species, diagnostic criteria, and treatment.

Nosocomial Rhinocerebral Mucormycosis: Two Cases with a Temporal Relationship.

Mucormycosis is an unusual fungal infection that usually affects immunosuppressed patients. Small outbreaks of mucormycosis have been previously reported. We present two clinical cases of fatal rhinocerebral mucormycosis with a close temporal relationship between them and a possible nosocomial transmission: case 1 was a 75-year-old male with diabetes and COPD, treated with antibiotics and systemic corticosteroids, who developed rhinocerebral mucormycosis. Case 2 was an 88-year-old woman who was treated with systemic antibiotics and corticosteroids and developed the same infection after insertion of a nasogastric tube. Both patients concurred at the same time in our hospital, and healthcare staff was common to both of them. These cases, along with previously reported cases, highlight that, although infrequent, transmission of the fungus in the hospital environment is a real possibility that should be taken into account in order to initiate contact and air isolation precautions that could avoid nosocomial transmission of this infection.

Meningitis Caused by Rhodotorula mucilaginosa in HIV-Infected Patient: A Case Report and Review of the Literature.

Rhodotorula species are increasingly being identified as a cause of fungal infection in the central nervous system, especially in patients with compromised immunity. The diagnosis could easily be missed due to low index of suspicion, as cryptococcus meningitis and cerebral toxoplasmosis are more common amongst immunocompromised hosts. To date, there are six cases of Rhodotorula-related meningitis reported, and three are associated with human immunodeficiency virus infection. In this report, a case of a Malaysian male with underlying human immunodeficiency virus infection who developed Rhodotorula mucilaginosa meningitis is presented. High-grade fever and severe headaches were the complaints presented in three previous case reports. India ink and nigrosin stainings were performed in the two previous reports and both revealed positive results. R. mucilaginosa were isolated from the culture of the patient's cerebrospinal fluid in all three previous reports. Predominant lymphocyte infiltration in the cerebrospinal fluid examination was documented in two reports. CD4 counts were above 100/µl in two previously published reports, while another report documented CD4 count as 56/µl. Amphotericin B and itraconazole are identified to be the first line of antifungal used and as the maintenance therapy, respectively. The possibility of relapse cannot be excluded as it was reported in the first report. It was also revealed that the current case has almost similar clinical presentation and therapeutic outcome as compared to the published reports, but some differences in diagnostic details were to be highlighted.

Lack of IL-6 increases blood-brain barrier permeability in fungal meningitis.

The pathogenesis of increased blood-brain barrier permeability during Cryptococcus meningitis is still largely unknown. Interleukin (IL-6) is a multifunctional cytokine, and numerous studies have shown that IL-6 influences the integrity of the blood-brain barrier. In this study we investigated the role of IL-6 in Cryptococcus meningitis. First, wild-type or IL-6(-/-) mice were injected with Cryptococcus neoformans (C. neoformans) and the survival time in both groups was recorded. Second, the number of fungi was measured in the brains of IL-6(-/-) wild-type mice. Finally, the blood-brain barrier permeability index was detected in infected IL-6(-/-) mice treated with recombinant human IL-6. The blood-brain barrier permeability index was measured in infected wild-type mice treated with anti-IL-6 antibodies as well. The survival of IL-6(-/-) mice injected with C. neoformans was significantly lower than that of identically challenged wild-type mice. The infected IL-6(-/-) mice had significantly larger brain fungal burdens than wild-type mice. Furthermore, increased blood-brain barrier index was found in infected IL-6(-/-) mice when compared with that in infected control mice. Similar results were obtained when mice challenged with C. neoformans were treated systemically with neutralizing anti-IL-6 antibodies, resulting in an elevation of vascular permeability. Our data revealed that IL-6 reduced the blood-brain barrier permeability during Cryptococcus meningitis, and it might provide an explanation for the significantly lower survival of infected IL-6(-/-) mice.

Infective meningitis caused by Phialemonium curvatum.

Infections caused by rarely encountered fungal pathogens have increased in recent decades. Phialemonium species are widely distributed in the environment and are also involved in human infections, affecting both immunocompromised and immunocompetent patients. The present study describes a case of meningitis caused by Phialemonium curvatum.

Clinical findings for fungal infections caused by methylprednisolone injections.

BACKGROUND: Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS: We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS: Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS: The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).

Chronic primary central nervous system histoplasmosis in a healthy child with intermittent neurological manifestations.

Meningitis is an unusual clinical manifestation of Histoplasma capsulatum infection in nonimmunosuppressed children. We report a previously healthy 6-year-old boy with primary, chronic histoplasma meningitis and magnetic resonance imaging findings consistent with demyelinating disease presenting with brief, intermittent neurological manifestations for 7 months before diagnosis.

Association between serum 25-hydroxyvitamin D level and type of coccidioidal infection.

The clinical manifestations of coccidioidomycosis vary depending upon the extent of exposure and immune status of the host. Recent studies have demonstrated an essential role for vitamin D in both innate and acquired immunity and serum levels strongly correlate with the development of upper respiratory tract infections, including tuberculosis. Despite similar pathophysiologic processes at play in the control of tuberculosis and invasive fungal infections, a possible association of low serum 25(OH) vitamin D levels had not previously been assessed in the latter patient group. Therefore, we performed a case-control study examining serum 25(OH) vitamin D levels in three distinct groups of patients with coccidioidomycosis as compared to healthy uninfected controls. Of the 89 patients included in this study, there were 26 negative controls, 23 who were immune, 22 with primary coccidioidal pneumonia, and 18 who had disseminated/meningeal infection. Serum 25(OH) vitamin D levels varied between groups with lowest levels seen in the group with disseminated/meningeal coccidioidomycosis (P= 0.14). In this evaluation of a diverse group of patients with varying forms of coccidioidomycosis we found no association of vitamin D with the acquisition or resolution of this infection. Vitamin D does not play a significant role in host susceptibility to coccidioidomycosis.

Aspergillus meningitis: a rare clinical manifestation of central nervous system aspergillosis. Case report and review of 92 cases.

OBJECTIVES: To describe the pathogenesis, clinical presentation, cerebrospinal fluid findings and outcome of Aspergillus meningitis, meningoencephalitis and arachnoiditis. METHODS: A case of Aspergillus meningitis is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of Aspergillus meningitis described between January 1973 and December 2011. RESULTS: Ninety-three cases (including the one described herein) of Aspergillus meningitis were identified. Fifty-two (55.9%) were in individuals without any predisposing factor or known causes of immunosuppression. Acute and chronic meningitis was diagnosed in 65.6% of patients and meningoencephalitis in 24.7% of them with the remaining presenting with spinal arachnoiditis and ventriculitis. Cerebrospinal fluid cultures for Aspergillus spp. were positive in about 31% of cases and the galactomannan antigen test in 87%. Diagnosis during life was achieved in 52 patients (55.9%) with a case fatality rate of 50%. The overall case fatality rate was 72.1%. CONCLUSIONS: Aspergillus meningitis may occur in both immunocompetent and immunocompromised patients and run an acute or chronic course. The findings of this systematic review extend the information on this life-threatening infection and could assist physicians in achieving an improved outcome.

Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings.

An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

Chronic fungal meningitis caused by Aureobasidium proteae.

We present a case of chronic meningitis due to the mold Aureobasidium proteae. Clinical features, the disease course, as well as the diagnostic methods and optimal treatment options are discussed. This case confirms the neuroinvasiveness of A. proteae and introduces it as a new human pathogen.

Allergic fungal sinusitis: innocence under suspicion.

The objective of this investigation was to explore the possibility of treating patients harboring invasive intracranial aspergillosis (InIA) at an early stage. Nineteen patients (age range 18-42 years) from a total of 114 cases of InIA seen from January 1999- December 2009 were included in this investigation. These individuals, all of whom had a past history of treated allergic fungal sinusitis (AFS) were evaluated as to their immune status, clinical presentations, time-intervals and radiological findings. Past records of seven patients indicated skull base erosion and extension of the paranasal (PNS) masses into intracranial cavity, but none had neurological deficits or symptoms suggestive of raised intracranial pressure. All 19 patients had undergone endoscopic clearance of PNS during their first presentations. Both AFS and InIA were found simultaneously in seven patients, while the time-interval between the two forms was as long as 10 years for two patients. Overall mortality was (8/19; 42%) with all deaths attributable to fungal meningo-encephalitis. As InIA carries a high mortality rate, it seems prudent to evaluate and treat these patients early in the course of their illness. The appearance of the invasive form of the disease in patients with a past history of AFS is not uncommon. The allergic form of disease may not be considered as a separate entity from InIA as both the pathologies may exist in same patient.

Efficacy of CG(3)R(6)TAT nanoparticles self-assembled from a novel antimicrobial peptide for the treatment of Candida albicans meningitis in rabbits.

BACKGROUND: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG(3)R(6)TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis. METHODS: In vitro activity of CG(3)R(6)TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG(3)R(6)TAT nanoparticles (n = 6; 0.25 mg/kg/day) or fluconazole (n = 6; 100 mg/kg/day) began 3 days after infection and continued for 11 consecutive days; the efficacy was assessed following 11 days of treatment by yeast counting in cerebrospinal fluid (CSF), the leukocyte concentrations in CSF and the histopathology of brain parenchyma. RESULTS: At a concentration three times higher than the minimum inhibitory concentration (8.1 µmol/l), the nanoparticles complete- ly sterilized C. albicans after 5 h of incubation. In addition, there was a significant reduction in fungal counts and leukocyte concentrations in the CSF from rabbits treated with CG(3)R(6)TAT nanoparticles or fluconazole versus those from untreated control rabbits (p < 0.05, ANCOVA). The median number of days of treatment required to sterilize CSF cultures was 8.5 days for CG(3)R(6)TAT nanoparticle therapy (p = 0.022, vs. control) and 9.7 days for fluconazole therapy (p > 0.05, vs. control). The histopathologic severity of rabbits was significantly attenuated after CG(3)R(6)TAT treatment (p = 0.001, vs. control). CONCLUSION: This study suggests that CG(3)R(6)TAT nanoparticles may be a promising therapeutic agent for candidal meningitis.