Brain death due to neuroaspergillosis in a patient with COVID-19.

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.

Impact of Surgical and Medical Treatment on Survival of Patients with Cerebral Aspergillosis: Systematic Review of the Literature.

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.

Aspergillus mural endocarditis presenting with multiple cerebral abscesses.

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 in an Immunocompetent Young Woman.

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.

Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

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.

Malignant fungal infection of the cavernous sinus: case report.

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.

Aspergilosis nasosinusal con extensión intracraneal en una paciente inmunocompetente: una entidad infrecuente con características radiológicas típicas / Sinonasal aspergillosis with intracranial extension in an immunocompetent patient: a rare disease with typical imaging features

El aspergilo es un hongo ubicuo. Las localizaciones de infección primaria más comunes son el tracto respiratorio y los senos paranasales. La afectación intracraneal es rara y conlleva una alta mortalidad. Ocurre mayoritariamente por extensión hematógena desde el pulmón, pero en pacientes inmunocompetentes, la extensión directa desde los senos paranasales es más común. Describimos el caso de una mujer de 25 años originaria de India que se presentó en el servicio de urgencia de nuestro centro hospitalario con cefalea frontal crónica y progresiva. Los hallazgos en los estudios de imágenes sugirieron el diagnóstico de sinusitis fúngica con extensión intracraneal, siendo el patógeno más frecuente el aspergilo. El diagnóstico fue confirmado anátomo-patológicamente. Revisamos los hallazgos radiológicos típicos que deben ayudar al diagnóstico precoz de esta entidad, rara, pero potencialmente mortal.

Aspergillus is a ubiquitous fungus. The most common primary sites of infection are the respiratory tract and sinuses. Intracranial infection is rare and implies a high mortality. It occurs mainly by hematogenous extension from the lung, but in immunocompetent patients, direct extension from the sinuses is more common. We describe the case of a 25 year old woman from India who consulted in the emergency room of our hospital with chronic and progressive frontal headache. The findings in imaging studies suggested the diagnosis of fungal sinusitis with intracranial extension, being the most common pathogen of Aspergillus. The diagnosis was anatomically-pathologically confirmed. We review the typical radiological findings which should help in the early diagnosis of this rare but potentially fatal disease.

Aspergillus brain abscess.

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.

Secretion of a fungal protease represents a complement evasion mechanism in cerebral aspergillosis.

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.

Resolution of secondary pulmonary alveolar proteinosis following treatment of rhinocerebral aspergillosis.

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.

Atypical presentation of chronic granulomatous disease in an adolescent boy with frontal lobe located Aspergillus abscess mimicking intracranial tumor.

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.

Cerebral aspergillosis presenting as a mass lesion.

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.

Aspergilose do sistema nervoso central após transplante hepático. Relato de caso / Cerebral aspergillosis in a liver transplanted patient. Case report

Introdução: O acometimento do sistema nervoso central pelo Aspergillus é muito grave e com alto índice de mortalidade. Relato de caso: Descrevemos o caso de uma paciente transplantada hepática em uso de imunossupressores que evoluiu com piora clínica. Tomografia computadorizada e ressonância magnética revelaram múltiplas lesões cerebrais. Em decorrência de má condição clínica da paciente, optou-se pelo tratamento conservador e em três dias ela evoluiu para óbito. Estudo anatomopatológico constatou quadro compatível com aspergilose. Discussão: Em pacientes imunossuprimidos, a suspeita precoce da infecção central fúngica é essencial para tentar evitar uma evolução catastrófica como no caso relatado.

Cerebral aspergillosis presenting as a mass lesion

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.

[Problematics of fungal infections in the ear]. / Problematyka zakazen grzybiczych w obrebie ucha.

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.

Invasive fungal granuloma of the brain caused by Aspergillus fumigatus: a case report and review of the literature.

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.

Isolated cerebral Aspergillus granuloma with no obvious source of infection.

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.