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.

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.

Spontaneous resolution of invasive cerebral aspergillosis following partial resection in a medically untreated infant.

Invasive craniocerebral aspergillosis, often encountered in an immunocompromised setting, is almost uniformly fatal despite radical surgical and medical management, and is frequently a necropsy finding. The authors report a unique, self-resolving clinical course of this aggressive infection in a 10-month-old infant. The infant was brought to the emergency services in altered sensorium with a 1-week history of left-sided hemiparesis, excessive irritability, and vomiting. An MRI study of the brain revealed multiple, heterogeneously enhancing lesions in the right cerebral hemisphere with mass effect. The largest lesion in the frontotemporal cortical and subcortical regions was decompressed on an emergent basis. Histopathological findings were suggestive of invasive aspergillosis, although there was no evidence of the infection in the lungs or paranasal sinuses. Computed tomography-guided aspiration of the remaining lesions and follow-up antifungal therapy were recommended. The parents, however, requested discharge without further treatment. The child was seen at a follow-up visit 3 years later without having received any antifungal treatment. Imaging showed resolution of the infection and features of Dyke-Davidoff-Masson syndrome (cerebral hemiatrophy). This report of invasive cerebral aspergillosis resolving without medical therapy is the first of its kind. Its clinicoradiological aspects are discussed in light of previously reported cases.

Severe cerebral aspergillosis after liver transplant.

Cerebral aspergillosis is a rare complication of liver transplantation. We present the case of a 34-year-old woman with multiple brain lesions discovered 8 days after orthotopic liver transplant for autoimmune hepatitis. The epidemiology, differential diagnosis, diagnostic strategies, and management of cerebral aspergillosis are discussed.

Diffusion-weighted imaging in brain aspergillosis.

Brain aspergillosis is a rare pathology, occurring mainly in immunocompromised patients, responsible for multiple cerebral septic infarctions. Some researchers have described magnetic resonance (MR) findings in cerebral invasive aspergillosis, but diffusion-weighted imaging (DWI) has rarely been reported, especially in typical non-enhancing lesions, while it may be helpful for early differential diagnosis and may allow earlier antifungal treatment. We describe three cases of patients presenting brain aspergillosis, with MR imaging including diffusion-weighted sequences and apparent diffusion coefficient (ADC) cartography. The three patients described in this study presented a total of 23 circular lesions, and one patient presented an infarction area in the territory of the right middle cerebral artery. Lesions were ring-enhancing for one patient, and presented no enhancement for the other two. Eleven lesions were very bright on DWI, with reduced ADC values. Twelve lesions, either enhancing or not enhancing, presented a 'target-like' aspect with central and peripheral hypointense areas on DWI, corresponding to higher ADC value areas, and intermediate marked hypersignal on DWI. This typical aspect of aspergillosis lesions on DWI may allow early diagnosis and treatment of cerebral aspergillosis, and is helpful for differentiating aspergillosis lesions from other infectious or malignant lesions affecting immunocompromised patients.

CNS aspergillosis: recognition, diagnosis and management.

Early diagnosis of CNS aspergillosis requires a high degree of clinical suspicion, because there are no typical clinical symptoms or CSF findings. Clinical features are usually dramatic and tend to progress rapidly. Changes in mental status, hemiparesis and seizures are most common, but other nonspecific neurological features may occur and should always be an indication for neuroradiological examination in high-risk patients, in order to allow early initiation of antifungal therapy. Low density lesions with little or no mass effect and minimal or no contrast enhancement on CT scans that are usually more numerous on MRI and show intermediate signal intensity within high-signal areas on T2-weighted images, may suggest CNS aspergillosis. Cerebral lesions in CNS aspergillosis are often located not only in the cerebral hemispheres but also in the basal ganglia, thalami, corpus callosum and perforator artery territories. There is frequently a lack of contrast enhancement or perifocal oedema, due to the immunosuppressed status of the patient. A definite diagnosis requires brain tissue for histopathological analysis. However, neurosurgery is often not feasible, so that any of the neuroradiological findings mentioned above should raise the suspicion of CNS aspergillosis in immunocompromised patients and lead to early initiation of antifungal therapy. In the past, amphotericin B-based therapy was the treatment of choice for CNS aspergillosis, but this treatment produced negligible effects. Recently, voriconazole has been reported to be more effective than amphotericin B in the treatment of invasive aspergillosis. Response rates of about 35% have been achieved with voriconazole in patients with CNS aspergillosis. Combination therapy with antifungal agents, such as voriconazole plus caspofungin or liposomal amphotericin B, is being investigated in vitro and in animal models, and optimistic results have been observed. A combined medical and neurosurgical treatment should be considered in all patients with this disease.

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.

Rhinocerebral aspergillosis cripple: high oral doses of Itraconazole was the solution.

Two cases of intracranial fungal infection, crippled with the recurrence of the fungal infection even after excisional surgery followed by intravenous Amphotericin B and oral Itraconazole are presented.

Middle and posterior fossa aspergilloma.

BACKGROUND: Aspergilloma of the brain is a rare disease. Among its varied presentations, a solitary intracranial mass is very uncommon. A preoperative diagnosis of it is very difficult, but a perioperative squash smear/frozen section can identify the pathology. Because of its rarity in immunocompetent patients and the difficulty in preoperative diagnosis, we have illustrated this case and its presentation and management. METHODS: A 27-year-old man presented with an h/o right-sided weakness along with headache and ear discharge. A computed tomographic (CT) scan showed a large irregular, space-occupying lesion in the middle and posterior cranial fossa. He had a mastoidectomy done 3 years before for chronic suppurative otitis media. After a symptom-free interval of 1 year, he was investigated for severe earache on the same side. A CT scan at that time showed a space occupying mass in the right temporal bone and right inferior temporal lobe. A biopsy and histopathology of the lesion revealed a chronic granulomatous mass. He was started on antituberculous drugs and was on it for 7 months at the time of presentation. RESULTS: He underwent a suboccipital craniectomy and total excision of the mass. Postoperatively, his consciousness improved but began to deteriorate on the third postoperative day. A repeat CT scan showed hydrocephalus and total removal of the mass. An external ventricular drain was put and he was ventilated, but he died on the fourth postoperative day. Histopathology report came as aspergilloma. CONCLUSION: This report highlights the rare presentation of aspergilloma in an immunocompetent patient. It emphasizes the importance of suspecting this disease in such patients and the role of intraoperative squash smear preparations or frozen section in the diagnosis as routine diagnostic procedures that will help in early pharmacotherapeutic interventions in adjunct to surgery.

Diagnostic MR imaging features of craniocerebral Aspergillosis of sino-nasal origin in immunocompetent patients.

BACKGROUND: Craniocerebral invasive Aspergillosis of sino-nasal origin has been reported with a very high mortality due to a peculiarly fulminant clinical course. Early diagnosis based on clinical radiological imaging may have an impact on final clinical outcome. This retrospective study focuses on characteristic MR imaging features of Aspergillosis (of sinonasal origin) in immunocompetent patients. METHODS: Medical records of patients were reviewed retrospectively during the period from 1991 to 2003 in the two tertiary care hospitals. All the patients had radiological evidence of disease in the paranasal sinuses with or without intracranial extension. Immunocompetence of patients was assessed on clinical and radiological data. MRI scans (n=20) were reviewed by both clinical neurosurgeons and neuroradiologists separately. MRI was done on 1.5 tesla scanners and both T2-weighted and T1 weighted sequences were obtained followed gadolinium enhanced images. Patients were categorized into three types based on their anatomical location on MRI scans; type-1 being intracerebral, type-2 as intracranial extradural and type-3 invading orbit and/or skull base only. All these patient had the epicenter of disease in the nose and/or paranasal sinuses as evident on MR imaging. All patients underwent standard surgical intervention followed by antifungal therapy. Clinical outcome was assessed on Glasgow outcome scale with mean duration of clinical follow up of 13.9 months. FINDINGS: Mean age of patents (n=20) was 31.1 years with male preponderance (3:1). MRI scans showed evidence of disease in paranasal sinuses including mucosal thickening (n=11) and complete filling of sinuses (n=9). T2-weighted images showed extremely hypo-intense fungal mass (n=19) while T1-weighted images had iso-intense signals (n=18). Gadolinium-enhanced images showed bright homogenous contrast enhancement (n=18) and peripheral ring enhancement pattern (n=2). All patients underwent appropriated surgical procedures depending upon anatomical location followed by standard antifungal therapy. Tissue diagnoses were established by histopathology (n=20) and culture growth (n=5). Overall mortality remained 15 percent. INTERPRETATION: Craniocerebral Aspergillosis of sinonasal origin has typical MR imaging features. These features include a mass lesion producing hypo-to-iso-intense signals on T1-weighted, extremely low signals (hypo-intense) on T2-weighted images, with bright homogenous enhancement on post-gadolinium T1-weighted imaging. These features in the clinical background may be helpful in early diagnosis and management of Aspergillosis of sino-nasal origin in immunocompetent hosts. Prospective clinical study is required to make firm clinical therapeutic recommendations.

A young woman with ring-enhancing lesions.

A non-neutropenic patient receiving corticosteroids for systemic lupus erythematosus presented with fever, headache, and seizures. Ring enhancing lesions were found on computed tomography of the brain, and biopsy demonstrated Aspergillus fumigatis. Despite treatment, the patient died, and necropsy revealed Aspergillus endocarditis of the mitral and tricuspid valves.

Brainstem auditory evoked response in adolescents with acoustic mycotic neuroma due to environmental exposure to toxic molds.

Indoor air contamination with toxic opportunistic molds is an emerging health risk worldwide. Some of the opportunistic molds include: Stachybotrys chartarum, Aspergillus species (A. fumigatus, A. flavus, A. niger, A. versicolor etc.), Cadosporium, Alternaria, Penicillium, Trichoderma, Fusarium graminearum etc. These molds flourish in homes that are moist and damp. Reports of floods are now evident in many parts of the world. With these global changes in climatic conditions that favor the opportunistic mode of living among these molds, some health authorities are beginning to feel concerned about the diversity and the extent to which opportunistic molds can cause adverse health effects in humans. Mycotoxicosis is the collective name for all the diseases caused by toxic molds. Frequently, we have cases of acoustic neuroma due to mycotoxicity in our Center. Mycotic neuroma probably has not been reported before and the application of brainstem auditory evoked response (BAER) techniques in acoustic mycotic neuroma have not been reported either. The aim of this study, therefore, was to report cases and measurements of acoustic mycotic neuroma in adolescents using the brainstem auditory evoked response. The patients' case history, clinical neurological and neurobehavioral questionnaires were assessed. Then, the BAERs were recorded between Cz and Ai, with a second channel, Cz-Ac. The case histories and the questionnaires were analyzed in conjunction with the outcome of the objective brainstem auditory evoked response measurements. The prevalent subjective findings in the patients were headaches, memory loss, hearing loss, lack of concentration, fatigue, sleep disturbance, facial swelling, rashes, nosebleeds, diarrhea, abdominal pains and respiratory difficulties. Objective BAER showed overall abnormalities in all the patients. Although the waveform abnormalities varied, 1-3 interpeak latencies were abnormal in all the patients. Overall results showed the presence of acoustic mycotic neuroma and confirmed the sensitivity and usefulness of BAER in screening acoustic mycotic neuroma and sensorineural auditory dysfunction.