Invasive Central Nervous System Aspergillosis Research Articles

A Case of Pulmonary and Central Nervous System Invasive Aspergillosis with Characteristic Radiological Findings

A Case of Pulmonary and Central Nervous System Invasive Aspergillosis with Characteristic Radiological Findings

Invasive Central Nervous System Aspergillosis in a Patient Receiving Long-term Acalabrutinib Therapy

Invasive Central Nervous System Aspergillosis in a Patient Receiving Long-term Acalabrutinib Therapy

Invasive aspergillosis of the central nervous system in immunocompetent patients in Saudi Arabia: Case series and review of the literature.

Objective:Invasive aspergillosis of the central nervous system in immunocompetent patients is a rare disease. We present in this study three cases that were treated in our centre and reviewed the results of similar studies from Saudi Arabia.Methods:We retrospectively reviewed all cases of invasive aspergillosis of the central nervous system (CNS) that were treated in our hospital in the last 10 years. We also reviewed the literature for any similar series published from Saudi Arabia.Results:We had three cases treated in our centre and we also found three similar case series in the literature. Total number of cases, including our series was 28, age range from 17 to 66, 10 men and 18 women. The source of infection was nasal sinuses in all cases. Initial presentations were variable and included headache (80% of cases), proptosis or diplopia (50% of cases), seizures (20% of cases), cranial nerve palsies (18% of cases) and acute deterioration in level of consciousness (18% of cases). All patients underwent surgery followed by long course of antifungal treatment. Clinical outcome was reported as cured or no recurrence in 13 cases (47%).Conclusions:Invasive aspergillosis of CNS is a rare disease in immunocompetent patients. Despite treatment prognosis remains unfavourable in many cases.

DISSEMINATED ASPERGILLOSIS IN A PATIENT WITH NEUROSARCOIDOSIS ON INFLIXIMAB

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Aspergillus fumigatus is a ubiquitous fungus associated with a variety of clinical syndromes. We report a case in which a patient with neurosarcoidosis but no underlying lung disease developed disseminated aspergillosis after starting infliximab therapy. CASE PRESENTATION: A 57 year old man with neurosarcoidosis on dexamethasone, infliximab, and methotrexate presented with two week history of shortness of breath and night sweats and one day history of right eye vision loss. Chest CT revealed new 3.6 cm cystic lung mass and three solid pulmonary nodules. MRI brain revealed innumerable ring-enhancing lesions in the right inferior frontal lobe measuring up to 3.7 cm. MRI spine revealed interval resolution of previously biopsied spinal granulomatous lesions. CSF studies and cultures were unremarkable. Serum Fungitell was > 500. Vitreous fluid culture from right eye and tissue culture from lung mass revealed Aspergillus fumigatus. The patient was treated with voriconazole. DISCUSSION: Aspergillus fumigatus is the most virulent species of Aspergillus. It is a ubiquitous saprotrophic fungus that can lead to a variety of clinical syndromes including allergic bronchopulmonary aspergillosis, aspergilloma, chronic cavitary pulmonary aspergillosis, invasive pulmonary aspergillosis, and disseminated aspergillosis. Severity of disease depends in part on size of inoculum, frequency of exposure, and host immune response. After inhalation, spores are removed by neutrophils and alveolar macrophages in normal hosts. Organisms that are not removed germinate into hyphae which are targeted by neutrophils. Given the significant role of neutrophils and macrophages in host defense against Aspergillus, immunodeficiency, particularly neutropenia and monocytopenia, represents the most significant risk factor for developing invasive aspergillosis. Other risk factors include underlying lung disease, critical illness, autoimmune diseases, and prolonged corticosteroid use. While lung disease is known to increase risk of invasive aspergillosis, our patient demonstrated neurosarcoidosis only, with no baseline pulmonary sarcoid involvement. Review of the literature reveals several case reports of fatal invasive aspergillosis with CNS involvement within months of starting infliximab therapy. TNFa inhibition has also been associated with poor fungal clearance and increased mortality in murine models of aspergillosis. These findings raise suspicion that TNFa inhibition may be an independent risk factor for the development of invasive aspergillosis. CONCLUSIONS: TNFa inhibition may be an independent risk factor for the development of invasive and disseminated aspergillosis, raising the question of whether screening or routine monitoring for fungal infections may be warranted for patients on anti-TNFa therapy. Reference #1: Tischler BY, Hohl TM. Menacing Mold: Recent Advances in Aspergillus Pathogenesis and Host Defense. J Mol Biol. 2019;431(21):4229–4246. doi:10.1016/j.jmb.2019.03.027. Reference #2: van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latgé JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017;15(11):661–674. doi:10.1038/nrmicro.2017.90. Reference #3: Bourne EL, Dimou J. Invasive central nervous system aspergillosis in a patient with Crohn's disease after treatment with infliximab and corticosteroids. J Clin Neurosci. 2016;30:163–164. doi:10.1016/j.jocn.2016.02.009. DISCLOSURES: No relevant relationships by Daniel Hershberger, source=Web Response No relevant relationships by Amber Johnson, source=Web Response

Role of Voriconazole in the Management of Invasive Central Nervous System Aspergillosis: A Case Series from a Tertiary Care Centre in India

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.

The fading boundaries between patient and environmental routes of triazole resistance selection in Aspergillus fumigatus.

Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary aspergillosis (CPA), and acute invasive aspergillosis (IA). Many patients suffering from aspergillus diseases benefit from antifungal therapy. Itraconazole, voriconazole, posaconazole, and isavuconazole have been shown to be the most effective compounds for prevention and treatment of the various aspergillus diseases. The use of alternative antifungal drugs, i.e., liposomal amphotericin B, is limited by toxicity and the echinocandins by fungistatic activity, while both also require intravenous access. As a consequence, the triazoles have become the recommended option for first-line therapy and chemoprophylaxis. Unfortunately, the effective use of triazoles has been threatened by the emergence of resistance in A. fumigatus. In voriconazole-treated patients, day 42 survival was 21% lower in voriconazole-resistant IA compared with voriconazole-susceptible infection. As the number of available drug classes is already very limited, some aspergillus diseases, such as central nervous system IA, are virtually untreatable if caused by a triazole-resistant isolate.

Invasive central nervous system aspergillosis in a patient with Crohn’s disease after treatment with infliximab and corticosteroids

Aspergillus species are emerging as a significant cause of pneumonia mortality in immune compromised hosts, with haematological spread being a rare and life-threatening complication. The central nervous system (CNS) as a site for extrapulmonary spread is rarer still. We report a case of CNS disseminated aspergillosis in a patient treated with corticosteroids and infliximab, an immunomodulatory agent commonly used in the treatment of inflammatory bowel disease, and review the available literature regarding this rare pathology.

Thoracic spinal cord intramedullary aspergillus invasion and abscess

Invasive central nervous system aspergillosis is a rare form of fungal infection that presents most commonly in immunocompromised individuals. There have been multiple previous reports of aspergillus vertebral osteomyelitis and spinal epidural aspergillus abscess; however to our knowledge there are no reports of intramedullary aspergillus infection. We present a 19-year-old woman with active acute lymphoblastic leukemia who presented with several weeks of fevers and bilateral lower extremity weakness. She was found to have an intramedullary aspergillus abscess at T12–L1 resulting from adjacent vertebral osteomyelitis and underwent surgical debridement with ultra-sound guided aspiration and aggressive intravenous voriconazole therapy. To our knowledge this is the first reported case of spinal aspergillosis invading the intramedullary cavity. Though rare, this entity should be included in the differential for immunocompromised patients presenting with fevers and neurologic deficit. Early recognition with aggressive neurosurgical intervention and antifungal therapy may improve outcomes in future cases.

Diagnostic Performance of an Aspergillus-Specific Nested PCR Assay in Cerebrospinal Fluid Samples of Immunocompromised Patients for Detection of Central Nervous System Aspergillosis

Central nervous system (CNS) invasive aspergillosis (IA) is a fatal complication in immunocompromised patients. Confirming the diagnosis is rarely accomplished as invasive procedures are impaired by neutropenia and low platelet count. Cerebrospinal fluid (CSF) cultures or galactomannan (GM) regularly yield negative results thus suggesting the need for improving diagnostic procedures. Therefore the performance of an established Aspergillus-specific nested polymerase chain reaction assay (PCR) in CSF samples of immunocompromised patients with suspicion of CNS IA was evaluated. We identified 113 CSF samples from 55 immunocompromised patients for whom CNS aspergillosis was suspected. Of these patients 8/55 were identified as having proven/probable CNS IA while the remaining 47 patients were classified as having either possible (n = 22) or no CNS IA (n = 25). PCR positivity in CSF was observed for 8/8 proven/probable, in 4/22 possible CNS IA patients and in 2/25 NoIA patients yielding sensitivity and specificity values of 1.0 (95% CI 0.68–1) and 0.93 (95% CI 0.77–0.98) and a positive likelihood ratio of 14 and negative likelihood ratio of 0.0, respectively, thus resulting in a diagnostic odds ratio of ∞. The retrospective analysis of CSF samples from patients with suspected CNS IA yielded a high sensitivity of the nested PCR assay. PCR testing of CSF samples is recommended for patients for whom CNS IA is suspected, especially for those whose clinical condition does not allow invasive procedures as a positive PCR result makes the presence of CNS IA in that patient population highly likely.

Diagnostic and therapeutic challenges in a liver transplant recipient with central nervous system invasive aspergillosis

This is a case report of central nervous system (CNS) invasive aspergillosis (IA) in a liver transplant recipient, which illustrates the utility of enzyme-based diagnostic tools for the timely and accurate diagnosis of IA, the treatment challenges and poor outcomes associated with CNS IA in liver transplant recipients.

Disseminated Invasive Aspergillosis with Multiple Brain Abscess after Allogeneic Hematopoietic Stem Cell Transplantation Treated Successfully with Voriconazole and Neurosurgical Intervention

Invasive aspergillosis is a serious infectious complication, which can occur after hematopoietic stem cell transplantation (HSCT). In particular, despite antifungal treatment, invasive aspergillosis involving the central nervous system (CNS) shows very high mortality. In principle, a neurosurgical procedure with an antifungal agent is recommended for treatment of CNS invasive aspergillosis. We encountered a patient suffering from disseminated invasive aspergillosis involving the lung, brain, and soft tissues after allogeneic HSCT for treatment of relapsed acute myeloid leukemia who was cured with voriconazole and stereotactic drainage of the brain abscess.

Poor Outcome of Central Nervous System Invasive Aspergillosis in HIV Infection Despite Galactomannan-Based Diagnosis

Invasive aspergillosis is recognized as a devastating disease in some immunocompromised populations, although it is not accepted as an established complication of human immunodeficiency virus/acquired immunodeficiency syndrome under the World Health Organization's staging criteria. Complications affecting the central nervous system are rarely reported, which may relate to a lack of adequate diagnostic tests. We report the use of the galactomannan Platelia assay in 3 patients with invasive cerebral infection and advanced human immunodeficiency virus, as defined by the World Health Organization, with CD4 T-lymphocyte counts of less than 350 cells/μL. The clinical use of the assay in early detection, particularly when used in a serial fashion, is compared to standard microbiological techniques. The limitations of the current assay are described in the context of future diagnostic approaches, such as sampling of cerebrospinal fluid and bronchoalveolar lavage specimens and the use of nucleic acid techniques. Copyright © 2011 by National Foundation for Infectious Diseases.

A case of invasive central nervous system aspergillosis treated with micafungin with monitoring of micafungin concentrations in the cerebrospinal fluid

Invasive aspergillosis has an extremely high mortality rate. In Japan, micafungin, an echinocandin drug that has a new mechanism of action as an antifungal agent and has a clinical effect against Aspergillus species, became available in 2002. However, little is known about its penetration into the central nervous system (CNS), or its efficacy for the treatment of invasive CNS aspergillosis. We report a 65-y-old female with diabetes mellitus and CNS aspergillosis who was treated with micafungin. During treatment, micafungin concentrations were measured in the cerebrospinal fluid and plasma. On a dose of 300 mg/d, the ratio of the micafungin concentration in the cerebrospinal fluid to that in plasma was extremely low (0.2%-0.05%); nevertheless, the patient did not have a relapse of invasive CNS aspergillosis after micafungin treatment.

Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview.

Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered.

Invasive Central Nervous System Aspergillosis

Invasive aspergillosis of the central nervous system is a rare but well-described disease. There have been only a few reported survivors, and mortality exceeds 95% in the immunosuppressed host. We present a 2-year-old boy with acute lymphatic leukemia and multiple Aspergillus brain abscesses who was successfully treated with liposomal amphotericin B, itraconazole, and surgical excision of the abscesses. Liposomal amphotericin B is a new preparation that safely allows the attainment of significantly higher tissue levels with less toxicity than standard amphotericin B. The treatment of patients with invasive central nervous system aspergillosis is reviewed.