Central Nervous System Aspergillosis Research Articles

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

Aspergillosis of the brain: diagnostic difficulties. Case report

Background: Neuroaspergillosis has nonspecific clinical manifestations and a severe course. Cases of central nervous system aspergillosis are becoming more frequent. Its lifetime diagnosis is very difficult. At the same time, a timely diagnosis makes it possible to conduct an adequate specific therapy and save the patient's life.
 Clinical case description: We report a clinical case of a patient with a lethal damage to the brain by filamentous fungi, who did not have the risk factors described in the literature human immunodeficiency virus (HIV), neutropenia, organ and tissue transplantation, long therapy with immunosuppressive drugs or corticosteroids.
 Conclusion: One needs to consider a possibility of this pathology in patients even in the absence of a fever and immunodeficiency conditions. A specific study of biological fluids for the presence of the galactomannan antigen may allow one to establish a timely correct diagnosis and apply an adequate treatment.

Diagnostic performance of noncultural methods for central nervous system aspergillosis.

Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.

Central nervous system aspergillosis misdiagnosed as Toxoplasma gondii encephalitis in a patient with AIDS: a case report

BackgroundPatients with acquired immunodeficiency syndrome (AIDS) tend to suffer from several central nervous system (CNS) infections due to hypoimmunity. However, CNS aspergillosis (CNSAG) is extremely rare and difficult to diagnose. Thus, it is easily misdiagnosed.Case presentationWe reported a 47-year-old male AIDS patient with ghosting vision and anhidrosis on the left head and face. He was accordingly diagnosed with Toxoplasma gondii encephalitis (TE) at other hospitals, for which he received regular anti-Toxoplasma gondii and anti-human immunodeficiency virus (anti-HIV) treatment. Then, the patient was transferred to our hospital due to a lack of any improvement with the prescribed treatment. The patient's neurological examination revealed no abnormalities at admission, only a slight change in the cerebrospinal fluid. His cranial magnetic resonance imaging (MRI) revealed multiple abnormal signals in the brain parenchyma, and his blood was positive for Toxoplasma gondii IgG antibody. The initial diagnosis at our hospital was also TE. Considering the poor efficacy of anti-TE treatment, cerebrospinal fluid metagenomics next-generation sequencing (mNGS) was performed, but no pathogenic bacteria were detected. However, Aspergillus fumigatus was detected in the cerebrospinal fluid via targeted next-generation sequencing (tNGS) and bronchoalveolar alveolar lavage fluid via mNGS. The diagnosis was accordingly revised to CNSAG combined with his other clinical manifestations. After administering voriconazole antifungal therapy, the patient’s symptoms were relieved, with improved absorption of the intracranial lesions.ConclusionsThe present case experience indicates the need for clinicians to strengthen their understanding of CNSAG. Moreover, for patients with diagnostic difficulties, early mNGS and tNGS (using biological samples with only a few pathogens) are helpful for early diagnosis and treatment, potentially allowing patients to achieve favorable outcomes.

Characterization of a rare clinical isolate of A. spinulosporus following a central nervous system infection

A rarely reported clinical specimen of Aspergillus spinulosporus was isolated from an immunocompetent 22-month-old boy who was suffering from central nervous system aspergillosis and meningitis. The patient had no comorbidity, organ transplantation, or other surgical operations that lead to invasive aspergillosis. A. spinulosporus is mostly a soil borne strain, and only three invasive aspergillosis cases involving this strain have been reported. We isolated this strain from cerebrospinal fluid, cultured it successfully on PDA medium, and named it BJCH M5. We performed a complete genomic and phenotypic analysis, evolutionary relationship, secondary metabolites analysis, identification of virulence factor, and pairwise synteny analysis. We sequenced the complete 31.6 MB genome of A. spinulosporus, including the eight chromosomes and mitochondria. 11,356 protein-coding genes were predicted. BJCHM 5 has a high sequence identity with ten virulent factors of Aspergillus fumigatus. It also encodes two unique BGCs (Biosynthetic gene clusters) which are involved in human infection. Pairwise synteny analysis demonstrated that this strain has chromosome arrangement differences from A. nidulans. In conclusion, we isolated a specimen of the rarely reported pathogen A. spinulosporus and performed a complete genome assembly and functional characteristic analysis.

Pulmonary and central nervous system aspergillosis in a patient with COVID-19 infection

Introduction. Patients with COVID-19 infection are vulnerable to a variety of serious complications, including invasive fungal infections such as aspergillosis. Because pulmonary aspergillosis is difficult to confirm with perfect confidence, it has been classified as ?proven,??probable,? and ?possible.? We present a patient with COVID-19 infection in whom a ?probable? pulmonary aspergillosis was complicated by hematogenous spread into brain with formation of multiple abscesses. Case outline. A 67-year-old female was diagnosed with COVID-19 infection using polymerase chain reaction (PCR) from a nasopharyngeal swab. The patient had never been vaccinated before. Despite standard therapy and noninvasive oxygen support, the patient?s health deteriorated one month following the onset of the disease, with chest discomfort, cough, and hemoptysis. Thoracic computed tomography (CT) revealed bilateral infiltrative lesions with varying diameters of cavities, primarily in the left lung, as well as modest effusions in both pleural spaces. Aspergillus hyphae were isolated from tracheobronchial aspirates. Despite therapy with Amphotericin B, which was only available antifungal medication at the time, the patient fell into a coma. A CT scan of the skull revealed several infiltrative lesions inside the brain, some with cavities suggestive to metastatic abscesses, most likely of fungal etiology (Aspergillus) as a result of hematogenous spread of pulmonary aspergillosis. Despite therapy and all other precautions, the patient died. The autopsy was not carried out. Conclusion. In addition to other complications, COVID-19 patients may develop pulmonary aspergillosis, which can be fatal because of the possibility of hematogenous spread to the brain.

Surgical treatment of ruptured right middle cerebral artery mycotic aneurysm and central nervous system aspergillosis: Clinical case and literature review

Background: Central nervous system (CNS) aspergillosis is more often met in patients with expressed immune suppression. Still, in 50% of cases of meningitis caused by Aspergillus spp., it is observed in patients without expressed immune suppression. The prognosis of CNS aspergillosis is unfavorable with the general rate of lethality around 70%.Case Description: Clinical case of a 58-year-old man who developed an Aspergillus abscess in the chiasmosellar region and an associated mycotic aneurysm of the right middle cerebral artery (MCA) and intracerebral hemorrhage. Microsurgical clipping of the fusiform-ectatic aneurysm of the right MCA in the conditions of rupture was performed. An extra-intracranial micro anastomosis was formed on the right. An open biopsy of the neoplasm in the chiasmosellar region was made. The neoplasm was yellow and destroyed the bone plate of the skull base. Biopsy results: Mycotic lesion (aspergillosis). The analysis of surgical treatment for mycotic aneurysms in the acute period of hemorrhage in patients with aspergillosis revealed a high rate of lethality. The issue of the feasibility and effectiveness of complicated revascularization interventions in the patients with hemorrhage and aspergillosis remains unsolved.Conclusion: The lack of generally accepted tactics of the treatment of this pathology requires further studies and systemic analysis. A high risk of the lethal outcome in patients with invasive mycotic infection and rupture of mycotic aneurysm highlight the importance of timely diagnostics and the beginning of antimycotic therapy. WThe issue of the evaluation of the revascularization methods effectiveness in patients after surgical treatment of a mycotic aneurysm associated with cerebral aspergillosis remains poor.

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.

Next generation sequencing for diagnosis of central nervous system aspergillosis in liver transplant recipients.

BackgroundFungal encephalitis is uncommon and sometimes fatal in liver transplant (LT) recipients. Early diagnosis of central nervous system (CNS) fungal infections, especially aspergillosis, is difficult based on routine tests of cerebrospinal fluid (CSF) alone. Next-generation sequencing (NGS) as a new tool may help in this respect.MethodsShotgun metagenomics was used to detect pathogens in CSF of patients, who were clinically suspected of CNS infection. Sequencing was performed at BGIseq-50 platform (BGI, Shenzhen).ResultsNGS technique identified Aspergillus in CSF of 5 patients, who were suspected of CNS infection, although clinical symptoms of these patients varied dramatically. The resulting sequence reads corresponding to Aspergillus species ranged from 2 to 25, with genomic coverage ranging from 0.0003% to 0.0036%. Rapid identification of Aspergillus enabled early appropriate antifungal therapy, although 4 patients eventually died of severe infection.ConclusionsThis is the first study to highlight the utility of NGS in early diagnosis of CNS aspergillosis in LT recipients. This new tool may be helpful in improving the diagnosis of CNS aspergillosis.

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.

Sino Cranial Aspergillosis Mimicking Skull Base Meningioma- A Case Report and Review of Literature

Fungal infections of the nose and paranasal sinuses can be categorised into invasive and noninvasive forms. Central Nervous System (CNS) Aspergillosis is extremely rare in immunocompetent individuals. Invasive fungal sinusitis affecting CNS commonly poses a diagnostic dilemma on imaging, often confused with neoplastic processes. Here, Authors report a case of invasive sino cranial aspergillosis in immunocompetent individual mimicking a meningioma on imaging. A 46-year-old male patient presented with history of seizure like episode and right eye proptosis to Neurology Department. On Magnetic Resonance Imaging (MRI), there was enhancing T2 weighted hypointense extra-axial mass lesion along right frontal convexity with associated osseous erosion, intraorbital extension and associated sinus disease. Based on clinical presentation and imaging features, initial diagnosis of a aggressive neoplastic lesion was made. Patient subsequently underwent biopsy which showed fungal elements of Aspergillus Fumigatus species. Patient underwent endoscopic sinus surgery and along intravenous and oral antifungal therapy with good response to treatment. This case highlights the key role of imaging including MRI and CT in making accurate diagnosis of fungal sinusitis especially in immunocompetent individuals and differentiate from other entities like meningioma.

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 ± 14.3 years) and 15 women (average age, 47.0 ± 19.4 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.

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

Aspergillosis infection over 20\u2009years: a case report of probable vascular invasion in central nervous system

BackgroundAspergillosis infection of central nervous system (CNS) is rare and fatal. Diagnosis of invasive aspergillosis remains difficult. Aspergillosis of CNS can be an acute, subacute, or chronic onset, and the longest course of the disease was currently reported to be 4 years. Here, we report a case with recurrent headache over 20 years.Case presentationA 54-year-old man was admitted to our neurological disease ward due to intermittent throbbing headache lasting for more than 20 years that had grown notably worse over the past week. The headache was localized to the side of his head blown by a cold wind. He also experienced nausea and vomiting when the headache became severe. The headache usually lasted for 3–4 h after he was blown by the cold wind, though he had no fever. The neurological examination was normal. Magnetic resonance imaging (MRI) of the brain was negative for parenchymal and meningeal lesions. However, the case had increased intracranial pressure (ICP), and elevated protein level in the cerebrospinal fluid (CSF). Aspergillus fumigatus was found in CSF by nanopore targeted sequencing (NTS) and in blood by enzyme-linked immunosorbent assay (ELISA). Aspergillus fumigatus-specific antibody IgG was 104.62 AU/mL, aspergillus galactomannan (GM) antigen was 3.27 μg/L, D-dimer was 3.25 mg/L and fibrinogen degradation product was 11.50 mg/L, which were markedly higher than the normal levels. The patient was prescribed by voriconazole. After the treatment of 14 days, the ICP, CSF protein level, Aspergillus fumigatus-specific antibody IgG, GM antigen, D-dimer and fibrinogen degradation product returned normal. Aspergillus was disappeared by NTS test of CSF. His headache has never occurred again after blowing by a cold wind.ConclusionsThis report reveals that aspergillosis infection of CNS can last for more than 20 years and the major symptom is only intermittent throbbing headache in an immunocompetent patient. Vascular invasion is probably the mechanism of headache in our case with CNS aspergillosis infection. Performing high-throughput gene sequencing technology in CSF is important when the pathogen is not determined for the patients with suspected CNS infection.

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.

Cerebral Aspergilloma in Patient with Diabetes – A Case Report with Short Literature Review

BACKGROUND: In the recent years, the incidence of fungal brain abscess has been rising as a result of the increased use of corticosteroid therapy, broad-spectrum antimicrobial therapy, and immunosuppressive agents. Aspergillosis of the central nervous system (CNS) is reported in 10%–20% of the patients having invasive fungal disease. Commonly, the disease is observed in immunocompromised or immunosuppressed patients; also, patients who suffered traumatic head injury are reported as well to develop the infection due to due cranial defect accompanied by dural tearing. Symptoms are non-specific neurologic manifestations.
 CASE PRESENTATION: We presented a case of a 68-year-old man who had diabetes mellitus type II. He was admitted to in neurosurgery clinic due reported head trauma. Initially, he complained of a headache, dizziness, slurred speech, nausea, and pain in the right ear with tinnitus and pain in his right upper teeth – continuous for a month. The patient was conscious, adequate, Glasgow Coma Scale – 15 points, with left-sided hemiparesis, general symptomatic syndrome. An emergent computed tomography scan was performed, which showed tumorous formation in patient’s right temporal lobe that had mass effect and compression of the right lateral ventricle. The patient was discussed on a emergent clinical counsel and it was decided that he was shown for surgical treatment. An informed consent was signed by the patient and his relatives. After the surgery intervention – the histological result of the biopsy was aspergilloma of the brain and the microbiological result was Aspergillus fumigatus.
 CONCLUSION: The prognosis for CNS aspergillosis is poor, but the early diagnosis and effective medical and surgical treatments may reduce morbidity and mortality.

Management of cerebral azole-resistant Aspergillus fumigatus infection: A role for intraventricular liposomal-amphotericin B

ObjectivesIn the pre-azole era, central nervous system (CNS) infections with Aspergillus had a dismal outcome. Survival improved with voriconazole but CNS infections caused by azole-resistant Aspergillus fumigatus preclude its use. Intravenous liposomal-amphotericin B (L-AmB) is the preferred treatment option for azole-resistant CNS infections but has suboptimal brain concentrations. MethodsWe describe three patients with biopsy-proven CNS aspergillosis where intraventricular L-AmB was added to systemic therapy. Two patients with azole-resistant aspergillosis and one patient with azole-susceptible CNS aspergillosis were treated with intraventricular L-AmB at a dose of 1mg weekly. ResultsWe describe three patients successfully treated with a combination of intravenous and intraventricular L-AmB. All three patients survived but one patient developed serious headaches, most likely not related to this treatment. ConclusionsIntraventricular L-AmB may have a role in the treatment of therapy-refractory CNS aspergillosis when added to systemic therapy.

Isolated central nervous system Aspergillosis infection in a chronic lymphocytic leukemia patient on Ibrutinib: A case report

BackgroundIn patients at high risk of opportunistic infections who present with isolated.neurological symptoms, it is lifesaving to consider Central Nervous System Aspergillosis (CNS-A). Ibrutinib use in chronic lymphocytic leukemia (CLL) has previously been associated with CNS-A. We provide a case report of a patient that presented with primary CNS-A on Ibrutinib therapy without any prior pulmonary or local paranasal signs of infection.Case presentation74-year-old Caucasian male with CLL and no prior chemotherapy on ibrutinib for 6 months presented with three months of unsteady gait, occipital headache, and confusion. He has a history of pulmonary sarcoidosis on chronic prednisone 5 mg daily and chronic obstructive pulmonary disease (COPD). He was found to have a “brain abscess” on imaging. Emergent craniotomy confirmed Aspergillus and patient was treated with Voriconazole for 6 months. At six-month follow up, repeat magnetic resonance imaging (MRI) confirmed complete resolution of CNS lesion.ConclusionsOur case reinforces the importance of being vigilant for isolated CNS-A in CLL patients on ibrutinib who present with neurological symptoms and signs, without prior or co-infection of sino-pulmonary tissue.

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Aspergilloma mimicking olfactory groove meningioma

Central nervous system aspergillosis is rare with reported mortality rate of 13–50% involving foci in paranasal sinuses and even higher mortality rates (80–100%) in patients of immune-compromised status. Modern day imaging offers an opportunity for early diagnosis, but findings are minimal. A typical finding is that of a space occupying mass lesion with iso-hypointense signal on T1-weighted sequences and extreme hypointense appearance on T2-weighted. This results from the concentration of ferromagnetic substances (iron/zinc/magnesium/manganese) within the lesion. Gadolinium enhancement pattern varies from homogeneous to peripheral ring enhancement. The immune-competent hosts present with homogeneous enhancement while those with immune compromise bear more variable radiological appearance. Due to such radiological appearance, meningioma or tuberculoma is considered in differential earlier than fungal granuloma, if not for the hypointense appearance on T2-weighted sequences which strongly points to fungal granuloma. Through this case report, we attempt to highlight the unusual radiological presentation of the entity.