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Co-infections between SARS-CoV-2 and other pathogens is an important consideration for the treatment of patients with COVID-19. Aspergillus infections are part of this consideration since they present high morbidity and mortality. We present the case of a patient with COVID-19 and Aspergillus Fumigatus coinfection that evolves with brain death due to multiple heterogeneous lesions in the brain, which after a post-mortem biopsy found pathological lesions compatible with Aspergillus., (Copyright © 2022 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Cerebral aspergillosis carries a high mortality. Rapid diagnosis and treatment can increase survival, but symptoms and imaging findings are nonspecific. The literature on cerebral aspergillosis consists mostly of case reports and case series and lacks large-scale review of data., Methods: We performed a review of the literature using PubMed in March 2019. We recorded the year of publication, age and sex of patients, neurosurgical involvement, the antifungals administered, use of intrathecal antifungals, and the outcome of patients. The relationships among variables were tested using bivariant statics and linear regression., Results: A total of 324 studies met the eligibility criteria, and 198 studies including 248 patients were included. Surgical resection (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.80; P < 0.01) and administration of voriconazole (OR, 0.32; 95% CI, 0.18-0.55; P < 0.001) or itraconazole (OR, 0.36; 95% CI, 0.16-0.72; P < 0.001) were shown to be significantly associated with survival., Conclusions: Given the significant survival benefits for patients who received voriconazole and surgical intervention, we suggest early antifungal medical treatment and resection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Fungal endocarditis is a rare and lethal cardiac infection which most commonly presents in immunocompromised patients or patients with other predisposing conditions. In a small subset of these patients, lesions present as mural masses and do not have any involvement with native valves or implanted devices. Here we present one such case which was diagnosed in the antemortem period in time to be managed with surgical resection., Case Presentation: A 70 year-old female patient who presented with multiple cerebral abscesses and was found on echocardiography to have a mass along the inferior wall of the left ventricle. She underwent surgical resection which revealed an Aspergillus vegetation along the left ventricle wall without any involvement of the cardiac valves. An intraoperative photograph was obtained and is presented in this case. The patient was started on antifungal therapy and expired on day 30 of treatment., Conclusions: Fungal endocarditis is a rare yet lethal disease. It can be difficult to detect and workup should be initiated immediately if there is any clinical suspicion. This is especially true in any patient with predisposing conditions or any patient who presents with undiagnosed, culture-negative fevers or evidence of embolic foci. Once diagnosis is made, early initiation of antifungal therapy coupled with aggressive surgical debridement is required for any significant chance of survival.

Intracranial aspergillosis (ICA) is very rare in the immunocompetent individuals, usually misdiagnosed as a tumor or an abscess. A high index of clinical suspicion is required in patients who present with focal neurological deficits, headache, or seizures. We report the case of a 25-year-old immunocompetent female, who presented with a 15-month history of headache, seizures, left-sided proptosis and ophthalmoplegia, and right hemiparesis. Recovery from the symptoms and decrease in the lesion size seen on the radiological assessment were achieved through two decompressive craniotomies followed by prolonged combined systemic antifungal therapies. Although the initial neuroimaging suggested a mitotic pathology, the surgical sample confirmed ICA. Now the patient is on single antifungal therapy (Tab. voriconazole, 200 mg twice daily) and doing her daily activities, but with a reduced intelligent quotient. We report a challenging case of ICA where multiple courses of combined antifungal therapies and repeat surgeries paved the way for a good prognosis.

Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

Intracranial spread of fungal infection is a life-threatening condition that usually affects immunocompromised patients. Here the authors present a case of biopsy-proven Aspergillus fumigatus infection of the paranasal sinuses in an immunocompetent patient with documented spread to the orbit, cavernous sinus, and petrous apex despite medical antifungal treatment. As a life-saving treatment, cavernous sinus resection with external carotid artery-middle cerebral artery bypass was performed. The authors discuss the literature regarding the intracranial spread of paranasal sinus fungal infections in immunocompetent patients and management strategies.

Aspergillus brain abscess is a rare clinical entity, which remains a challenge to diagnose and treat. Most fungi are low virulence organisms, often living as commensals. They however, pose a considerable challenge in an immune-compromised host. Systemic steroids are commonly used in treatment of various inflammatory conditions. Despite their relatively safe profile, one peril of such treatment is immune suppression. It is prudent that physicians remain aware of the risk of various opportunistic infections in such patients. We present a case of fatal intra-cranial aspergillosis in an immuno-compromised patient on systemic steroids.

Pulmonary alveolar proteinosis can be secondary to inhaled dust exposure, malignancy, and chronic pulmonary infections. However, pulmonary alveolar proteinosis secondary to extrapulmonary aspergillosis has never been reported. We report herein a case of pulmonary alveolar proteinosis secondary to invasive rhinocerebral aspergillosis. Neither immune modulators nor whole lung lavage was applied during the treatment course. The severe respiratory distress subsided, hypoxia resolved, and radiological infiltrates improved following the successful treatment of invasive rhinocerebral aspergillosis alone., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Complement represents a central immune weapon in the brain, but the high lethality of cerebral aspergillosis indicates a low efficacy of the antifungal complement attack. Studies with cerebrospinal fluid (CSF) samples derived from a patient with cerebral aspergillosis showed a degradation of complement proteins, implying that Aspergillus might produce proteases to evade their antimicrobial potency. Further investigations of this hypothesis showed that Aspergillus, when cultured in CSF to simulate growth conditions in the brain, secreted a protease that can cleave various complement proteins. Aspergillus fumigatus, the most frequent cause of cerebral aspergillosis, destroyed complement activity more efficiently than other Aspergillus species. The degradation of complement in CSF resulted in a drastic reduction of the capacity to opsonize fungal hyphae. Furthermore, the Aspergillus-derived protease could diminish the amount of complement receptor CR3, a surface molecule to mediate eradication of opsonized pathogens, on granulocytes and microglia. The lack of these prerequisites caused a significant decrease in phagocytosis of primary microglia. Additional studies implied that the complement-degrading activity shares many characteristics with the previously described alkaline protease Alp1. To improve the current therapy for cerebral aspergillosis, we tried to regain the antifungal effects of complement by repressing the secretion of this degrading activity. Supplementation of CSF with nitrogen sources rescued the complement proteins and abolished any cleavage. Glutamine or arginine are of special interest for this purpose since they represent endogenous substances in the CNS and might be included in a future supportive therapy to reduce the high lethality of cerebral aspergillosis., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Chronic granulomatous disease (CGD) is an uncommon congenital phagocyte disorder characterized by recurrent life-threatening infections. CGD generally present with recurrent suppurative infections, however, intracranial fungal abscess complicating CGD may cause a diagnostic problem to anyone unfamiliar with its clinical and radiological features., History: We report the case of a 16-year-old boy who was consulted with a differential diagnosis of an intracranial tumor. The clues of his medical history and physical examination made us consider the diagnosis of CGD. Cytometric dihydrorhodamine assay and genotyping confirmed an autosomal recessive CGD. He was successfully treated without any complication or sequel for 18 months follow-up period with surgery and interferon-gamma, in addition with, liposomal amphotericin B and voriconazole that were found to be sensitive to the Aspergillus fumigates, which had been grown from the culture of the abscess cavity., Discussion: We discuss the pathogenesis, radiological techniques, and management of cerebral Aspergillus abscess in a patient with CGD., Conclusion: Presentation of CGD with a cerebral Aspergillus abscess, mimicking a brain tumor is extremely rare in children; clinicians and neurosurgeons must be aware. The best management modality for cerebral Aspergillus abscess is to be vigilant about the disease, whereas adjuvant surgical and medical therapy with a close follow-up must be warranted for all cases.

Fungal infections of the central nervous system (CNS) are almost always a surprising finding. Their presentation is usually subtle, often without any diagnostic characteristics, and they are frequently mistaken for pyogenic abscesses, or brain tumors. Aspergillosis of the central nervous system is an uncommon infection, mainly occurring in immunocompromised patients. It may present in several forms, including meningitis, mycotic aneurysms, infarcts and a tumoral form. We report an intracranial granuloma due to Aspergillus fumigatus involving the anterior cranial fossa and the frontal lobe. The clinical symptoms began one year before admission. Final diagnosis was made after craniotomy. The patient was treated with an extensive excision of the cerebral mass and medical antifungal therapy (intravenous amphotericin B), but she failed to respond to these treatments and died.

Background: Involvement of the brain by Aspergillus fumigatus, named as invasive aspergillosis, is extremely rare. Definitive diagnosis needs isolation of the fungus from the tissue specimens and its culture. The disease is very resistant to treatment and quickly becomes fatal despite antifungal chemotherapy with AmB preparations, the drugs of choice for the infection., Case Description: We hereby present a unique case of fungal granuloma of the brain due to A fumigatus, which was cured successfully by intensive antifungal treatment, along with a brief literature review., Conclusions: Although it is rare, we draw the attention to the fact that early diagnostic procedures with rapid confirmation of Aspergillus infection and an early initiation of therapy are pivotal for a benign clinical course in such cases. A complete regression of the disease could be achieved with medical therapy alone with conventional AmB or liposomal AmB combined with oral itraconazole even if a total surgical excision of the lesions could not be performed in complicated cases, as in our patient.

Fungal infections of the ear are recognised quite rarely, but they make sometimes, for many reasons, very important diagnostic-therapy issue. Cantagion may developes in every elements of the ear, ranging from external ear (external canal ear, sometimes auricle), middle ear (every pneumatic structure) to iner ear (extra ordinary rarely). Every states, which weaken general and punctual immunity (like immunosupression, chemo-sterydotherapy, blood disease, pregnancy and HIV) are circles, which give facilities to invansion. After penetrated organism, course of infections, in case of type of patogens, trim of the patient and localization, can have without symptoms, sharp, chronic or fulminant shape. For the sake of morphological differentiation fungal, in their developing cycle, treatment mycosis recommends serious difficulty, extra factor, which impeds therapy, is a must of prolongely antifungal treatment and repeated (to total elimination) remove hyphae from ear, which stay sometimes even for week. Progress of the mycotic infections ear, remain bacterial infections and is often reason of bad diagnosis and incorrect treatment.

Objective: Central nervous system (CNS) aspergillosis is a life-threatening disease that has had a published mortality of >80%. Little is known about this serious infection in the pediatric population. We conducted this study to analyze characteristics of CNS aspergillosis in infants and children., Methods: The English literature was reviewed and all CNS aspergillosis cases in patients younger than 18 years of age were analyzed., Results: Ninety cases were recorded up to June 2005. The median age of the patients was 9 years, ranging from 18 days to 18 years (15.6% younger than 1 year). CNS aspergillosis most commonly presented as brain abscess(es), either single or multiple. While prematurity was the predominant underlying condition among infants, leukemia was the most frequent underlying disease in children. Aspergillus fumigatus was isolated from 75.5% of the cases. The overall mortality in published cases was 65.4%. In multivariate analysis, surgical treatment was independently associated with survival., Conclusion: CNS aspergillosis in infants and children predominantly presents as brain abscess(es) and has significantly better outcome compared to published adult data. The findings of this systematic review could assist future investigations for improved outcome of this life-threatening infection in pediatric patients.

Background: Intracranial fungal granulomas occur by extension from contiguous structures or by hematogenous dissemination from lungs. Isolated granulomas without any obvious source of infection are extremely uncommon., Objective: To describe isolated intracerebral Aspergillus spp. granuloma without any obvious source of infection., Materials and Methods: We analyzed clinical, radiological and pathological features of isolated intracerebral aspergillus granulomas diagnosed in our institution between 1986 and 2006. The chest X-ray and paranasal sinus (PNS) X-rays were reviewed. Fungal stainings were done on histological sections., Results: We identified eight patients with Aspergillus spp. intracerebral granulomas (six males, two females). There were no predisposing risk factors. The chest and PNS X-rays were normal. On computerized tomography all were heterogeneously enhancing lesions with perilesional edema. Pre or perioperative diagnosis was never made. Histological studies revealed granulomas with minimal fibrosis and giant cells and septate hyphae of Aspergillus spp. on fungal stains. Two patients died of postoperative complications and two patients relapsed., Conclusion: Isolated intracerebral aspergillus granulomas are rare and pose a diagnostic challenge. Fungal granulomas should be considered in the differential diagnosis of intracerebral inflammatory pathologies.

Early diagnosis of CNS aspergillosis requires a high degree of clinical suspicion, because there are no typical clinical symptoms or CSF findings. Clinical features are usually dramatic and tend to progress rapidly. Changes in mental status, hemiparesis and seizures are most common, but other nonspecific neurological features may occur and should always be an indication for neuroradiological examination in high-risk patients, in order to allow early initiation of antifungal therapy. Low density lesions with little or no mass effect and minimal or no contrast enhancement on CT scans that are usually more numerous on MRI and show intermediate signal intensity within high-signal areas on T2-weighted images, may suggest CNS aspergillosis. Cerebral lesions in CNS aspergillosis are often located not only in the cerebral hemispheres but also in the basal ganglia, thalami, corpus callosum and perforator artery territories. There is frequently a lack of contrast enhancement or perifocal oedema, due to the immunosuppressed status of the patient. A definite diagnosis requires brain tissue for histopathological analysis. However, neurosurgery is often not feasible, so that any of the neuroradiological findings mentioned above should raise the suspicion of CNS aspergillosis in immunocompromised patients and lead to early initiation of antifungal therapy. In the past, amphotericin B-based therapy was the treatment of choice for CNS aspergillosis, but this treatment produced negligible effects. Recently, voriconazole has been reported to be more effective than amphotericin B in the treatment of invasive aspergillosis. Response rates of about 35% have been achieved with voriconazole in patients with CNS aspergillosis. Combination therapy with antifungal agents, such as voriconazole plus caspofungin or liposomal amphotericin B, is being investigated in vitro and in animal models, and optimistic results have been observed. A combined medical and neurosurgical treatment should be considered in all patients with this disease.

Background: Aspergilloma of the brain is a rare disease. Among its varied presentations, a solitary intracranial mass is very uncommon. A preoperative diagnosis of it is very difficult, but a perioperative squash smear/frozen section can identify the pathology. Because of its rarity in immunocompetent patients and the difficulty in preoperative diagnosis, we have illustrated this case and its presentation and management., Methods: A 27-year-old man presented with an h/o right-sided weakness along with headache and ear discharge. A computed tomographic (CT) scan showed a large irregular, space-occupying lesion in the middle and posterior cranial fossa. He had a mastoidectomy done 3 years before for chronic suppurative otitis media. After a symptom-free interval of 1 year, he was investigated for severe earache on the same side. A CT scan at that time showed a space occupying mass in the right temporal bone and right inferior temporal lobe. A biopsy and histopathology of the lesion revealed a chronic granulomatous mass. He was started on antituberculous drugs and was on it for 7 months at the time of presentation., Results: He underwent a suboccipital craniectomy and total excision of the mass. Postoperatively, his consciousness improved but began to deteriorate on the third postoperative day. A repeat CT scan showed hydrocephalus and total removal of the mass. An external ventricular drain was put and he was ventilated, but he died on the fourth postoperative day. Histopathology report came as aspergilloma., Conclusion: This report highlights the rare presentation of aspergilloma in an immunocompetent patient. It emphasizes the importance of suspecting this disease in such patients and the role of intraoperative squash smear preparations or frozen section in the diagnosis as routine diagnostic procedures that will help in early pharmacotherapeutic interventions in adjunct to surgery.

Background: Craniocerebral invasive Aspergillosis of sino-nasal origin has been reported with a very high mortality due to a peculiarly fulminant clinical course. Early diagnosis based on clinical radiological imaging may have an impact on final clinical outcome. This retrospective study focuses on characteristic MR imaging features of Aspergillosis (of sinonasal origin) in immunocompetent patients., Methods: Medical records of patients were reviewed retrospectively during the period from 1991 to 2003 in the two tertiary care hospitals. All the patients had radiological evidence of disease in the paranasal sinuses with or without intracranial extension. Immunocompetence of patients was assessed on clinical and radiological data. MRI scans (n=20) were reviewed by both clinical neurosurgeons and neuroradiologists separately. MRI was done on 1.5 tesla scanners and both T2-weighted and T1 weighted sequences were obtained followed gadolinium enhanced images. Patients were categorized into three types based on their anatomical location on MRI scans; type-1 being intracerebral, type-2 as intracranial extradural and type-3 invading orbit and/or skull base only. All these patient had the epicenter of disease in the nose and/or paranasal sinuses as evident on MR imaging. All patients underwent standard surgical intervention followed by antifungal therapy. Clinical outcome was assessed on Glasgow outcome scale with mean duration of clinical follow up of 13.9 months., Findings: Mean age of patents (n=20) was 31.1 years with male preponderance (3:1). MRI scans showed evidence of disease in paranasal sinuses including mucosal thickening (n=11) and complete filling of sinuses (n=9). T2-weighted images showed extremely hypo-intense fungal mass (n=19) while T1-weighted images had iso-intense signals (n=18). Gadolinium-enhanced images showed bright homogenous contrast enhancement (n=18) and peripheral ring enhancement pattern (n=2). All patients underwent appropriated surgical procedures depending upon anatomical location followed by standard antifungal therapy. Tissue diagnoses were established by histopathology (n=20) and culture growth (n=5). Overall mortality remained 15 percent., Interpretation: Craniocerebral Aspergillosis of sinonasal origin has typical MR imaging features. These features include a mass lesion producing hypo-to-iso-intense signals on T1-weighted, extremely low signals (hypo-intense) on T2-weighted images, with bright homogenous enhancement on post-gadolinium T1-weighted imaging. These features in the clinical background may be helpful in early diagnosis and management of Aspergillosis of sino-nasal origin in immunocompetent hosts. Prospective clinical study is required to make firm clinical therapeutic recommendations.

We report an unusual case of brain aspergillosis with multiple recurrent abscess in a 40 year-old immunocompetent woman, with good therapeutical outcome. The patient presented a subarachnoid hemorrhage caused by a ruptured pericallosal artery aneurysm and was submitted to a craniotomy for aneurysm surgery. Five months later, she developed multiple Aspergillus cerebral abscess. Two craniotomies and amphotericin B became necessary during treatment. Fourteen years later, she is asymptomatic. Treatment of brain aspergillosis abscess implied the combination of both surgical and drug therapy with amphotericin B.

Aspergillosis of the central nervous system (CNS) is a rare condition with exceedingly high mortality. This study describes the case of an immunocompetent 42-year-old man with a history of intravenous drug use and hepatitis C who developed multiple Aspergillus lesions in the cerebellum. Despite neurosurgery and antifungal therapy with amphotericin B, he had a protracted hospital course with multiple complications, eventually developing cognitive and motor impairment due to progressive cerebellar lesions. After transfer to hospice and palliative care service, oral itraconazole was escalated to 1600 mg/day with the hope of palliating headache, nausea, and cognitive impairment. Remarkably, the patient stabilized and improved over time. After 14 months, this unprecedented high-dose regimen was discontinued, and the patient was discharged home with only mild cerebellar motor impairment.

We describe in detail a 67-yr-old woman who was treated with a cytostatic combination chemotherapy for newly diagnosed common-acute lymphoblastic leukaemia. At the end of induction therapy, the patient acquired invasive mould infection affecting lung and brain. The patient entered complete remission of her leukaemia. Treatment with liposomal amphotericin B was initiated along with surgical excision of the fungal brain abscess. Intrathecal instillation of amphotericin B deoxycholate was started using an Ommaya reservoir because of an anatomical connection between the postoperative cavity and the ventricle. Full dose cytostatic chemotherapy was continued with little delay. A computerised tomography scan of the chest performed 2 months later revealed no fungal abscesses. Magnetic resonance imaging of the brain did not reveal any fungal manifestation. During maintenance therapy/week 69, the patient relapsed from leukaemia. High doses of intravenous liposomal amphotericin B were administered prophylactically. The patient's leukaemia proved refractory to reinduction chemotherapy and the patient died from pneumonia 8 wk later. Post mortem microbiological investigation and histopathological examination of lung and brain tissue did not reveal any macroscopical or microscopical fungal manifestations. This case underlines the feasibility and successful application of combined antileukaemic, antifungal and surgical therapy in a patient with acute leukaemia.

Invasive aspergillosis remains a life-threatening complication in immunocompromised patients. The pulmonary involvement by the aspergillosis is the most common setting. The dissemination of the disease is correlated with the worse prognosis. The overall improvement of the prognosis needs a global diagnostic and therapeutic strategy. In neutropenic patients (mostly at risk of invasive aspergillosis), an early diagnosis can be achieved by systematic use of thoracic CT scan to search halo sign (that seems to be quite specific of the diagnosis in this setting). The early initiation of the antifungal treatment (conventional or liposomal amphotericin or new azole compounds) could be combined with a surgical approach if necessary. This approach could be able to improve the prognosis of aspergillosis. However, the outcome of these patients remains also correlated to the underlying disease.