Central Nervous System Aspergillosis Research Articles

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.

CNS aspergilloma mimicking tumors: Review of CNS aspergillus infection imaging characteristics in the immunocompetent population

Background and purposeCNS Aspergillosis is very rare and difficult to diagnose clinically and on imaging. Our objective was to elucidate distinct neuroimaging pattern of CNS aspergillosis in the immunocompetent population that helps to differentiate from other differential diagnosis. MethodsRetrospective analysis of brain imaging findings was performed in eight proven cases of central nervous system aspergillosis in immunocompetent patients. Immunocompetent status was screened with clinical and radiological information. Cases were evaluated for anatomical distribution, T1 and T2 signal pattern in MRI and attenuation characteristics in CT scan, post-contrast enhancement pattern, internal inhomogeneity, vascular involvement, calvarial involvement and concomitant paranasal, cavernous sinus or orbital extension. All patients were operated and diagnosis was confirmed on histopathology. ResultsThe age range was 19–50 years with mean age of 33.7 years. Concomitant sinonasal disease was seen in six patients (75%). Three patients had orbital extensions. Most of the lesions (n=7) were profoundly hypointense in T2-weighted imaging. The most common enhancement pattern was bright, solid and homogenous enhancement (n=7). Cavernous extension with ICA encasement was always associated with paranasal sinus disease. Six patients showed demineralization or complete resorption of involved bone. All of the fungal masses appear hyperdense on available CT scan images. ConclusionCNS aspergillus infection in immunocompetent patients has distinct imaging features as compared to CNS aspergillosis in immunocompromised patients. A high index of suspicion in proper clinical settings, even with immunocompetent status and typical imaging features allow us to diagnose CNS aspergillosis in such patients.

Resolution of aspergillosis in neuroimaging of an immunocompromised patient with pulmonary and cerebral lesions

Central nervous system (CNS) aspergillosis is uncommon and considered the most lethal form of aspergillosis. Indeed, current therapeutic strategies such as combination antifungal regimen, neurosurgical resection of infected tissue, and removal of infection source fail to improve the unsatisfactory prognosis of CNS aspergillosis in the majority of the patients. The authors describe a case of chronic pulmonary aspergillosis with concomitant CNS lesions that dramatically responded to antifungal therapy and the CNS lesions resolved in follow-up imaging.

Need of voriconazole high dosages, with documented cerebrospinal fluid penetration, for treatment of cerebral aspergillosis in a 6-month-old leukaemic girl

This case report indicates the usefulness of voriconazole for the treatment of central nervous system (CNS) aspergillosis, also in paediatrics. However, it also confirms the need for therapeutic drug monitoring (TDM), especially in younger children that may require very high dosages in order to achieve plasma and cerebrospinal fluid (CSF) therapeutic concentrations.

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

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

Clinical Features and Magnetic Resonance Imaging Findings in 7 Dogs with Central Nervous System Aspergillosis.

BackgroundSystemic aspergillosis is a manifestation of Aspergillus sp. infection that can result in central nervous system (CNS) involvement with marked alterations in CNS function. Information regarding the clinical presentation and magnetic resonance imaging (MRI) findings in cases of aspergillosis with CNS involvement is lacking, resulting in a need for better understanding of this disease.Hypothesis/ObjectivesThe primary objectives were to describe the clinical features and MRI findings in dogs with CNS aspergillosis. The secondary objectives were to describe clinicopathologic findings and case outcome.AnimalsSeven dogs with CNS aspergillosis.MethodsArchived records from 6 institutions were reviewed to identify cases with MRI of CNS aspergillosis confirmed with serum galactomannan enzyme immunoassay (EIA) testing, culture, or supported by histopathology. Signalment, clinical, MRI, clinicopathologic, histopathologic, and microbiologic findings were recorded and evaluated.ResultsAspergillosis of the CNS was identified in 7 dogs from 3 institutions. The median age was 3 years and six were German Shepherd dogs. Five dogs had signs of vestibular dysfunction as a component of multifocal neurological abnormalities. The MRI findings ranged from normal to abnormal, including hemorrhagic infarction and mass lesions.Conclusions and Clinical ImportanceUntil now, all reported MRI findings in dogs with CNS aspergillosis have been abnormal. We document that CNS aspergillosis in dogs, particularly German Shepherd dogs, can be suspected based on neurologic signs, whether MRI findings are normal or abnormal. Confirmatory testing with galactomannan EIA, urine, cerebrospinal fluid (CSF) or tissue culture should be performed in cases where aspergillosis is a differential diagnosis.

Cough and confusion in an elderly man with chronic lymphocytic leukemia

Cough and confusion in an elderly man with chronic lymphocytic leukemia

Invasive Fungal Granuloma of the Brain in an Immunocompetent Patient

Aspergillus species is a fungus that causes invasive diseases with high mortality in immunosuppressed patients. We present a case of the central nervous system aspergillosis in an immunocompetent patient. A 27-year-old man was admitted to the hospital with complaints of headache and visual disturbance. He was a known case of fungal sinusitis and used to inhale opium. In cranial magnetic resonance imaging, a mass lesion in the right frontal lobe was observed. The pathology result was in favor of the aspergillus infection. The substance abuse by inhalation is considered a possible route of fungal entry, especially in the immunocompetent patient.

Aspergillus flavus induces granulomatous cerebral aspergillosis in mice with display of distinct cytokine profile

Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.

髄液アスペルギルス抗原価を指標として治療をおこない，脳梗塞を合併したにもかかわらず長期生存がえられた中枢神経アスペルギルス症の1例

Central nervous system (CNS) aspergillosis with stroke has a high mortality and poor prognosis generally. We report a 78-years-old woman with diabetes mellitus, who developed invasive paranasal sinus aspergillosis with the orbital apex syndrome on the right side and cerebral infarction caused by intracranial occlusion of the right internal carotid artery. Based on the presence of a mass lesion in the ethmoid sinus extending to the orbital apex on the right side with cranial CT, the mass lesion was surgically removed and the pathological examination of the surgical specimen revealed aspergillus mold. Immediately after surgery, we initiated treatment with voriconazole 200 mg × 2/day intravenously for 38 days, and then via feeding tube for 86 days until the galactomannan-aspergillus antigen level in the cerebrospinal fluid became negative at 132 days. She is alive now for almost two years without relapse of aspergillosis. There is no definitive guideline for management of patients with CNS aspergillosis concerning the length of drug treatment and the method for monitoring the response for treatment. We believe that measurement of the galactomannan-aspergillus antigen level in the cerebrospinal fluid might be a useful way of monitoring the efficacy of treatment for CNS aspergillosis.

Thoracic spinal cord intramedullary aspergillus invasion and abscess

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

Improving Outcomes in Cerebral Aspergillosis

solated intracerebral aspergillosis without a focus of disease in the sinuses or the lungs and in the absence of immunoI compromise due to disease or medications is extremely rare. A confirmatory absence of systemic aspergillosis can be obtained using computed tomography or magnetic resonance imaging (MRI), both of which are significantly more sensitive than conventional x-rays for detecting infection in either the sinuses or the lungs. Because of the uncommon occurrence of this infection in healthy individuals, most articles represent case reports demonstrating a successful clinical outcome after a combination of surgical and medical management. In the current issue of WORLD NEUROSURGERY is one of the few series that contains several patients that were identified over a 15-year interval. The clinical course of central nervous system (CNS) aspergillosis is distinctly different in immunocompetent patients when compared to their immunosuppressed counterparts. The clinical course for a patient with CNS aspergillosis is much more benign when an intact immune system is present with recoveries being uneventful in contrast to the horrific experience endured by those with immune compromise. In addition, the survival rates for the immunocompetent patients without systemic involvement are in the range of 80%e90% in contrast to the 5%e30% rates that are often seen in immunocompromised patients.

Screening of the central nervous system in children with invasive pulmonary aspergillosis

The existing guidelines regarding the management of invasive pulmonary aspergillosis do not recommend screening of the extra-pulmonary sites. Due to the fact that the presence of central nervous system (CNS) aspergillosis will influence treatment decisions regarding which antifungal to use and the aimed target concentrations of azoles in plasma, to be informed about dissemination of the infection to the CNS is absolutely necessary. We demonstrate the need for a structured approach to screening of pediatric patients for CNS aspergillosis.

Fatal Invasive Aspergillosis in Acute Lymphoblastic Leukemia Patient

Invasive aspergillosis (IA) is one of the most common fungal infections in immunocompromised patients. Is an air-borne disease and the majority of patients develop pneumonia or sinusitis. However central nervous system (CNS) aspergillosis may also occur. Infections by Aspergillus fumigatus are most prevalent although in recent years, non-fumigatus Aspergillus species such as A. flavus has become common as causal agents this mycosis. The major risk factors associated include neutropenia, hematological malignancy,andtransplantation of hematopoietic stem cells and solid organs. Therefore, here we report a fatal case of pulmonary aspergillosis and CNS due Aspergillus flavus in neutropenic patient with acute lymphoblastic leukemia. The diagnosis of pulmonary infection was based in the isolation of A. flavus in tracheal secretions associated with the pulmonary infiltration detected in the Chest X-ray. Because of the thrombocytopenia the CNS aspergillosis was diagnosed only by brain magnetic resonance imaging. This case underscores the Importance of IA as a serious disease and late diagnosis leading to a poor prognosis with fatal course due to worsening clinical.

Cerebral aspergillosis in adult critically ill patients: a descriptive report of 10 patients from the AspICU cohort

An unexpectedly high incidence of invasive pulmonary aspergillosis (IPA) has been reported in non-neutropenic intensive care unit (ICU) patients. After the respiratory tract, the brain is most often affected by invasive aspergillosis. However, little is known about brain involvement by Aspergillus in critically ill patients. In this study, demographics, risk profile, diagnosis, treatment and outcome of proven cases of invasive cerebral aspergillosis (ICA) taken from a cohort of 563 adult patients with evidenced Aspergillus involvement during their ICU stay were reviewed. Ten patients with central nervous system aspergillosis were identified. All had one or more host factors predisposing for invasive aspergillosis. The clinical and radiological presentation was non-specific and exclusively pulmonary-related. All but one patient had proven or probable/putative IPA. On cerebral computed tomography, lesions appeared as either solitary and hyperdense or were multiple and randomly distributed throughout the brain. One patient presented with sole meningeal infestation. Aspergillus infection was confirmed by brain biopsy in three subjects. Voriconazole was used as primary treatment in only one-half of the patients. Mortality was 90%. ICA is not frequently observed in adult ICU patients. Diagnosis must be considered in patients at risk presenting with proven or probable/putative IPA in association with suggestive neuroradiological findings. The brain is most likely affected through haematogenous dissemination from the lungs. Current treatment recommendations are not always applied and outcome remains dismal.

Antifungal Therapy of Aspergillosis of the Central Nervous System and Aspergillus Endophthalmitis

Cerebral Aspergillosis is the most lethal manifestation of infection due to Aspergillus species arising most commonly as hematogenous dissemination from a pulmonary focus, direct extension from paranasal sinus infection or direct inoculation through trauma and surgery of the central nervous system (CNS). Voriconazole is currently considered the standard of treatment of CNS aspergillosis with liposomal amphotericin B being the next best alternative. Neurosurgical resection of infected cerebral tissue in addition to antifungal therapy is frequently performed in patients with CNS aspergillosis to prevent neurological deficits and improve outcome. Aspergillus endophthalmitis may occur endogenously mostly from a pulmonary focus or exogenously following eye surgery or trauma. Although amphotericin B is still described as the primary therapy, voriconazole is increasingly considered the first line treatment of Aspergillus endophthalmitis. Vitrectomy is recommended in most cases of Aspergillus endophthalmitis.

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

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

Cerebral Aspergillosis with Multiple Enhancing Nodules in the Right Cerebral Hemisphere in the Immune-Competent Patient

Aspergillosis in the central nervous system (CNS) is a very rare disease in immune-competent patients. There was a case of a healthy man without a history of immune-compromised disease who had invasive aspergillosis with unusual radiologic findings. A 48-year-old healthy man with diabetes mellitus, presented with complaints of blurred vision that persisted for one month. Brain magnetic resonance imaging (MRI) showed multiple nodular enhancing lesions on the right cerebral hemisphere. The diffusion image appeared in a high-signal intensity in these areas. Cerebrospinal fluid examination did not show any infection signs. An open biopsy was done and intraoperative findings showed grayish inflammatory and necrotic tissue without a definitive mass lesion. The pathologic result was a brain abscess caused by fungal infection, morphologically aspergillus. Antifungal agents (Amphotericin B, Ambisome and Voriconazole) were used for treatment for 3 months. The visual symptoms improved. There was no recurrence or abscess pocket, but the remaining focal enhanced lesions were visible in the right temporal and occipital area at a one year follow-up MRI. This immune-competent patient showed multiple enhancing CNS aspergillosis in the cerebral hemisphere, which had a good outcome with antifungal agents.

Iatrogenic Fungal Meningitis: Tragedy Repeated

The recent reports of fungal meningitis caused by contaminated corticosteroid injections are a reminder of the importance of sterility and the disease-producing interactions between corticosteroids...

Central Nervous System Aspergillosis

Central nervous system (CNS) aspergillosis is a highly fatal infection. We review the clinical presentation, diagnosis, and outcome of this infection and present a case series of 14 consecutive patients with CNS aspergillosis admitted to Massachusetts General Hospital (MGH) from 2000 to 2011. We also review 123 cases reported in the literature during that time. We included only proven CNS aspergillosis cases conforming to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal infections. In the MGH case series, neutropenia, hematologic malignancies, autoimmune diseases requiring steroid treatment, and solid organ transplantation were the predominant comorbid conditions. Notably, all MGH patients were immunosuppressed, and more than half (n = 8) had a history of previous brain injury, unrelated to their index hospitalization. For most MGH patients (11 of 14), the lung was the primary focus of aspergillosis, while 2 had paranasal sinus involvement, and 1 had primary Aspergillus discitis. Among reported cases, paranasal sinuses (27.6%) and the lung (26.8%) were the primary foci of infection, whereas 22% of those cases had no obvious primary organ involvement. Although a selection bias should be considered, especially among published cases, our findings suggest that patients who underwent neurosurgery had improved survival, with MGH and literature patients having 25% and 28.6% mortality, respectively, compared to 100% and 60.4%, respectively, among patients who received only medical treatment. Although this was not the case among MGH patients, CNS aspergillosis can affect patients without significant immune suppression, as indicated by the high number of reported immunocompetent cases. In conclusion, mortality among CNS aspergillosis patients remains high, and the infection may be more common among patients with previous brain pathology. When indicated, neurosurgical procedures may improve prognosis.