Longitudinally extensive posterolateral myelitis revealing invasive CNS aspergillosis in an immunocompetent patient.

BACKGROUND: Fungal infections of the central nervous system usually affect immunocompromised patients. Primary Aspergillus myelitis has never been described. REPORT: A 45-year-old immunocompetent male with subacute paraplegia was treated for inflammatory myelitis before clinical deterioration requiring mechanical ventilation. Purulent meningitis preceded the formation of a paraspinal nodule biopsied by neurosurgery. Histopathological analysis revealed the presence of fungal hyphae, and polymerase chain reaction was positive for Aspergillus fumigatus. No cause of immunodeficiency was identified in this patient. DISCUSSION: Primary Aspergillus myelitis may be confused with inflammatory myelitis and should be considered even in the absence of apparent immunosuppression.

Muerte cerebral debida a aspergilosis cerebral en un paciente de COVID-19 / Brain death due to neuroaspergillosis in a patient with COVID-19

Las coinfecciones entre SARS-CoV-2 y otros patógenos son una cuestión importante para el tratamiento de los pacientes con COVID-19. Las infecciones por Aspergillus forman parte de esta consideración, ya que presentan elevada morbimortalidad. Presentamos el caso de un paciente con coinfección de COVID-19 y Aspergillus fumigatus que evolucionó a muerte cerebral debido a múltiples lesiones heterogéneas en el cerebro donde, tras biopsia post-mórtem, se encontraron lesiones patológicas compatibles con Aspergillus.(AU)

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.(AU)

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.

Clinical manifestations, diagnosis, and treatment outcome of CNS aspergillosis: A systematic review of 235 cases.

Aspergillus is a ubiquitous ascomycete that can cause a variety of clinical presentations depending on immune status. Central nervous system aspergillosis is a fatal disease with non-specific clinical features. The aim of this systematic review was to evaluate the epidemiology, clinical features, diagnosis and therapeutic interventions in CNS aspergillosis patients. We also aimed to examine the possible predictors of mortality in neuroaspergillosis. Literature search was performed in Medline, PubMed, and Google scholar and all patients≥18 years with proven CNS aspergillosis were included. A total of 175 articles (235 patients) were included in the final analysis. Their mean age was 51 years and the majority were male (57.4%). Overall case-fatality was 45.1%. Aspergillus fumigatus was the most common species (70.8%) followed by A. flavus (18.6%). Corticosteroids (22.6%), malignancy (19.1%) and diabetes mellitus (14%) were the most common risk factors. Neuroimaging findings included cerebral abscess (70.2%), meningitis (14%), infarction (13.2%) and mycotic aneurysm (8.9%). Disseminated disease (29.2% vs 17.8%, p 0.03), CSF hypoglycorrhachia (48.1% vs 22.2%, P: 0.001) and heightened CSF galactomannan (3.62 vs 2.0ng/ml, p 0.05), were the factors associated with poor outcome in neuroaspergillosis. Persons infected with Aspergillus flavus (13.1% vs 3.1%, P: 0.01), and having been treated with Voriconazole (51.9% vs 29.2%, P: 0.004) were more likely to survive. Our review will provide insight into the different spectrums of CNS aspergillosis. Notwithstanding the promising role of Voriconazole, future work is required to ascertain the role of combination antifungal therapy.

Diagnosis of central nervous system invasive aspergillosis in a liver transplant recipient using microbial cell-free next generation DNA sequencing.

Invasive aspergillosis (IA) is an important opportunistic infection among patients with liver disease and liver transplants. Diagnosis of IA may be challenging, especially among patients with central nervous system infection. Herein, we demonstrate the utility of next-generation sequencing of microbial cell-free DNA in the diagnosis of fungal brain abscess in a liver transplant recipient.

Lung aspergilloma with pituitary invasive aspergillosis presenting as headache and hyponatraemia.

Fungal infections involving the pituitary gland are rare and can be life threatening. A 75-year-old man with hypertension and diabetes mellitus presented with headache and hyponatraemia. Imaging study showed right upper lung mass, and mass resection showed aspergilloma without tissue invasion on histology. The patient developed visual impairment a few weeks later, and MRI of the brain revealed bilateral sphenoid sinusitis and pituitary invasion. The trans-sphenoidal biopsy confirmed invasive Aspergillus infection. His sphenoidal sinuses were endoscopically debrided, and he was treated with oral voriconazole. Pituitary aspergillosis should be considered in the differential diagnosis in patients with lung aspergilloma with headache and sinusitis. Prompt biopsy and antifungal treatment are important due to the high mortality rate of the infection.

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.

Invasive pulmonary aspergillosis with brain dissemination in an immunocompetent host

Invasive aspergillosis is an uncommon infection, which is mainly seen among immunocompromised patients. In recent years, cases of aspergillosis involving immunocompetent hosts are increasingly being reported. Herein, we report the case of a 27-year-old man with fever, productive cough, shortness of breath, and left hemiparesis. He had suffered trauma to his head 25 days prior. Imaging of the chest showed bilateral cavitary lesions in the lungs, and neuroimaging revealed a space-occupying lesion in the right frontoparietal cerebrum. He was suspected of having an abscess or metastasis. He died on day 3 of hospitalization, and an autopsy was performed. The autopsy revealed the cause of death to be invasive pulmonary aspergillosis, with brain dissemination. Invasive aspergillosis is uncommon in apparently immunocompetent individuals, and we discuss the autopsy findings in detail.

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.

Cerebral and pulmonary aspergillosis, treatment and diagnostic challenges of mixed breakthrough invasive fungal infections: case report study.

BACKGROUND: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia. CASE PRESENTATION: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy. CONCLUSIONS: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.

Invasive rhino-orbital-cerebral aspergillosis in an immunocompetent patient.

INTRODUCTION: Rhino-orbital-aspergillosis (ROA) is a rare but serious disease in immunocompetent patients. Diagnosis is often delayed due to the absence of specific clinical symptoms. We describe the case of a patient who presented initially with ROA which spread progressively to the right ethmoid-sphenoid sinuses and then to the brain. OBSERVATION: A 61-year-old patient with a history of well-controlled diabetes presented with a sudden severe decrease in right visual acuity. Cerebral MRI showed the presence of an infiltrate in the right orbital apex extending to the homolateral cavernous sinus without any cerebral involvement. A diagnosis of right orbital myositis was made and corticosteroid therapy was started. His symptoms worsened progressively leading to quasi-blindness. A new MRI showed the development of right sphenoid-ethmoid osteolytic lesions. A fungal aetiology was suspected and tests for fungal biomarkers found a ß-(1-3)-D-glucan level of 99pg/ml but negative galactomannan. An ethmoid biopsy was performed for histological and mycological investigations, including the detection of Aspergillus DNA by qPCR. qPCR was positive and culture resulted in the isolation of multi-sensitive Aspergillus fumigatus. Treatment was initiated with voriconazole. Due to persistence of blindness and the appearance of a lesion extending to the right frontal lobe, surgical excision was performed followed by antifungal treatment for a total duration of 1year. The patient is currently stable, but has persistence of blindness in the right eye. CONCLUSION: Invasive ROA is a rare but serious disease in immunocompetent patients which should be evoked in the differential diagnosis of a tumour or vasculitis. Early diagnosis is essential for optimal management.

Percutaneous transforaminal endoscopic discectomy for the treatment of lateral recess stenosis secondary occurred the discal fungus infection.

BACKGROUND: This is a case of lateral recess stenosis secondary occurred the discal fungus infection treated with percutaneous transforaminal endoscopic discectomy (PTED). There has been no relevant reports before. CASE PRESENTATION: A 49-year-old patient who had taken itraconazole for 13 months for lateral recess stenosis secondary occurred the discal fungus infection complained of gradually worsening radiating pain and numbness in the back and inguinal and inner thigh region of right side. In order to relieve the radiating neuralgia and reduce the damage to spinal stability, the minimally invasive PTED was performed.The patient's prognosis was assessed using Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS). During the follow-up, the patient's ODI and VAS scores were decreased significantly. The radiating pain in the inguinal and inner thigh region of right side were significantly alleviated and the discomfort caused by lower back instability was improved by plaster vest. DISCUSSION AND CONCLUSION: PTED not only avoids further damage to the stability of the lumbar spine, but also effectively relieves the symptoms of leg neuroradialgia caused by lateral recess stenosis secondary occurred the discal fungus infection.

Holohemispheric Invasive Aspergillus Granulomatous Cerebritis of the Brain.

BACKGROUND: Invasive aspergillosis of the central nervous system, a saprophytic infection with a unique vascular tropism, carries the burden of increased morbidity and mortality. Early clinical and imaging findings can masquerade as an innocuous condition before a secondary inexorable progression. We highlight the clinical and imaging phenotype of a patient with fatal invasive granulomatous aspergillosis. CASE DESCRIPTION: A 39-year-old man presented with progressive weakness of the left upper and lower limb for 4 months. Imaging demonstrated right holohemispheric extensive, numerous, confluent, ill-defined, T2 hypointense foci with moderate perilesional edema. Numerous foci of microhemorrhages with cortical asymmetric mineralization were seen. Post-contrast heterogeneous, variegate, punctiform enhancement of the lesions was observed extending to the ventricular margins. Volume loss of the left cerebral peduncle and ipsilateral long white matter descending tracts was noted. Histopathologic examination of a stereotactic biopsy specimen from the frontal region lesion showed dense inflammatory infiltrate with granulomas, a few in a perivascular distribution and branching septate hyphae resembling Aspergillus. The patient was initiated on antifungal therapy and in the following week, he had progressive drowsiness. The patient succumbed the next day. CONCLUSIONS: Diffuse holohemispheric, progressive presentation of a granulomatous form of invasive aspergillosis is a rare entity. The miliary pattern of heterogenous enhancement, holohemispheric conglomerate T2 hypointensities, interspersed hemorrhage, juxtacortical punctate T2 hyperintense foci, low perfusion, and the relative absence of diffusion abnormality are distinctive features. Early diagnosis of this atypical imaging phenotype of Aspergillus infection and appropriate treatment is critical for better prognosis.

Isavuconazole Treatment of Cerebral and Pulmonary Aspergillosis in a Pediatric Patient With Acute Lymphoblastic Leukemia: Case Report and Review of Literature.

Invasive aspergillosis in hematologic pediatric patients is an opportunistic infection that is difficult to treat, with a high mortality rate when localized in the central nervous system. We are describing a 3-year-old girl who was affected by acute lymphoblastic leukemia who developed cerebral and pulmonary aspergillosis during induction chemotherapy. The patient failed first-line voriconazole treatment because of being a CYP2C19 ultrarapid metabolizer and received effective isavuconazole therapy with no notable side effects.

Infantile Aspergillus fumigatus ventriculitis successfully treated with monitoring of plasma and cerebrospinal fluid voriconazole concentration level.

Aspergillosis is a rare fungal infection in newborns, and its morbidity and mortality are high. Voriconazole (VRCZ) is the first-line antifungal agent for invasive Aspergillus infection, but little data is available about its pharmacokinetics in infants. We report a case of a premature infant who developed ventriculitis due to Aspergillus fumigatus and received combination antifungal therapy including VRCZ. ß-D glucan and Aspergillus antigen index were elevated in the cerebrospinal fluid (CSF). We titrated the dose of VRCZ by monitoring plasma and CSF concentrations. The CSF to plasma concentration ratio of VRCZ ranged from 0.47 to 1.36 (median 0.71). While VRCZ adequately penetrates the blood-brain barrier, its concentration is highly variable in infants.