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.

Acute Stroke as First Manifestation of Cerebral Aspergillosis.

OBJECTIVES: To describe the neurological manifestations of invasive aspergillosis presenting with a focal neurological deficit compatible with an acute stroke. MATERIALS AND METHODS: Retrospective analysis of a clinical series of patients between 2011 and 2017 with invasive aspergillosis and neurological symptoms compatible with an acute brain stroke. Clinical and epidemiological data, microbiological results, radiological findings, treatment, and course were recorded. RESULTS: Five patients were selected with a mean age of 55.4years. All patients were immunosuppressed. In 4, systemic infection was unknown. In every case, neurology on call was alerted because of acute focal neurological symptoms. None of the patients received revascularization procedures. Galactomannan antigen was positive in all of the patients and culture was positive in 3. Mortality was 100% despite specific antifungal treatment. CONCLUSIONS: Acute stroke can be the first manifestation of disseminated aspergillosis. This form of presentation was frequent in our series and should be suspected in immunocompromised patients with acute neurological deficits.

Risk factors for invasive aspergillosis and related mortality in recipients of allogeneic SCT from alternative donors: an analysis of 306 patients.

Invasive aspergillosis (IA) is a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), particularly from donors other than HLA-identical sibling. All 306 patients who underwent alternative donor HSCT between 01 January 1999 and 31 December 2006 were studied. Late IA was defined as occurring >or=40 days after HSCT. The median follow-up was 284 days (range, 1-2709). Donors were matched unrelated (n=185), mismatched related (n=69), mismatched unrelated (n=35) and unrelated cord blood (n=17). According to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, 2 patients already had IA at HSCT, 23 had early IA and 20 had late IA (IA incidence 15%). Eight patients had proven and 37 probable IA. Multivariate analyses showed that significant predictors of IA were delayed neutrophil engraftment, extensive chronic GVHD (cGVHD), secondary neutropenia and relapse after transplant. Early IA was associated with active malignancy at HSCT, CMV reactivation and delayed lymphocyte engraftment. Late IA was predicted by cGVHD, steroid therapy, secondary neutropenia and relapse after HSCT. IA-related mortality among IA patients was 67% and was influenced by use of anti-thymocyte globulin, steroids, higher levels of creatinine, and lower levels of IgA and platelets. The outcome of IA depends on the severity of immunodeficiency and the status of the underlying disease.

Poor efficacy of amphotericin B-based therapy in CNS aspergillosis.

Recently, improved response and survival rates in patients treated with voriconazole and neurosurgery for central nervous system (CNS) aspergillosis have been reported. We assessed retrospectively the outcome in 17 patients with definite or probable CNS aspergillosis treated with amphotericin B alone (n = 15) or in combination with 5-fluorocytosine (n = 3) or itraconazole (n = 2). Four patients underwent neurosurgery. The mortality rate was 100% with a median survival of only 10 days (range: 3-60) after onset of first symptoms or first radiological evidence of CNS aspergillosis. In conclusion, treatment with amphotericin B and itraconazole has negligible efficacy in CNS aspergillosis.

Relevant imaging findings of cerebral aspergillosis on MRI: a retrospective case-based study in immunocompromised patients.

The aim of the study was to assess neuroimaging patterns of cerebral aspergillosis with magnetic resonance imaging (1.5 T). The clinical and imaging data of nine patients were reviewed. Patients were included in the study if the diagnosis of aspergillosis was confirmed by either biopsy, autopsy, aspergillus antigen determination and/or neuroradiological and clinical response to specific treatment. Four patients had single or multiple abscesses presenting as ring-enhancing lesions on T1-weighted images, hypointensity of the ring on T2-weighted MR images and low to high signal intensity on diffusion-weighted imaging. Four patients had single or multiple infarctions affecting all compartments of the brain with hyperintensities on T2-weighted images in three of four patients, irregular parenchymal contrast enhancement in all patients and hemorrhagic transformation of the infarcted parenchyma in one patient. Diffusion-weighted images were positive in all ischemic areas. One patient with paranasal sinusitis developed a mycotic aneurysm of the internal carotid artery. Cerebral aspergillosis presents three principal neuroimaging findings: areas consistent with infarction; ring lesions consistent with abscess formation following infarction; and dural or vascular infiltration originating from paranasal sinusitis or orbital infiltration. Recognition of these patterns in cerebral aspergillosis may lead to more timely and effective diagnosis and treatment.

Improved survival in central nervous system aspergillosis: a series of immunocompromised children with leukemia undergoing stereotactic resection of aspergillomas. Report of four cases.

Central nervous system (CNS) aspergillosis remains a daunting diagnosis. This opportunistic mycosis historically carries a mortality rate approaching 100% in immunocompromised patients, with death ensuing within days after the onset of neurological symptoms. From their literature review, the authors concluded that children contracting CNS aspergillosis while undergoing systemic chemotherapy for leukemias represent a particularly unfortunate prognostic group. Antifungal medications prove ineffective for treating CNS aspergillosis in patients immunocompromised because of their chemotherapy regimens. In contrast, withholding chemotherapy to reverse immunosuppression, thereby improving the efficacy of antifungal medications, allows for progression of the primary leukemic disease. The authors present a series of four immunosuppressed patients whose course of treatment for leukemia was complicated by CNS Aspergillus sp. abscesses. Multiple cerebral fungal abscesses developed in two patients and a single cerebral abscess developed in two. All four patients underwent frameless stereotactic resection of the aspergilloma. All children later experienced resolution of their CNS infections and full neurological recovery. At 2- to 4-year follow ups, one patient has died of leukemia and the other three continue to thrive without evidence of recurrent aspergillosis. Given the grave natural history cited in the literature for this disease when medical treatment is instituted alone, the authors stress the crucial role of stereotactic neurosurgery for the intelligent treatment of immunocompromised children suspected of harboring a CNS aspergilloma abscesses. The authors propose that the goal for successful treatment in these patients should be gross-total resection of the abscess, its wall, and its capsule.

Aspergillus parasellar abscess mimicking radiation-induced neuropathy. Case report.

BACKGROUND: Transsphenoidal surgery is a safe procedure for treatment of pituitary adenomas. However, several complications, including post-surgical infection, are known. We describe a case of Aspergillus parasellar abscess that presented with cranial neuropathies following transsphenoidal surgery and radiosurgery. We initially diagnosed the case as radiation-induced neuropathies, which delayed the detection of Aspergillus. CASE DESCRIPTION: A 55-year-old man underwent transsphenoidal surgery for a pituitary adenoma that presented with pituitary apoplexy. Dexamethasone had been continuously administered for hypocortisolism probably caused by pituitary apoplexy. Four years later, radiosurgery was performed for a relapse in the right cavernous sinus. Another 4 years later, he developed painful right ophthalmoplegia, right ptosis, and bilateral visual impairment, successively. We initially suspected that the painful ophthalmoplegia and ptosis were because of radiation-induced cranial neuropathies; however, results of magnetic resonance (MR) imaging and his clinical course were not consistent with those of radiation-induced neuropathies. Therefore, we performed exploratory surgery that revealed a subdural abscess on the planum sphenoidale. Culture of a specimen grew Aspergillus fumigatus. CONCLUSION: Intracranial fungal abscess is a fatal complication unless it is treated early. It is thus important to consider the possibility of parasellar infection and differentiate it from radiation-induced cranial neuropathies when a patient presents with cranial neuropathies after transsphenoidal surgery and radiosurgery.