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.

The Muddied Waters of Ibrutinib Therapy.

A 37-year-old male was admitted with an atypical presentation of central nervous system (CNS) aspergillosis while on ibrutinib therapy for a CNS relapse of mantle cell lymphoma. This case highlights the importance of a high clinical suspicion of opportunistic infections in patients receiving small-molecule kinase inhibitors. This report includes a review of reported cases of Aspergillus infections in patients receiving ibrutinib and the shared features of these cases.

Successful and safe long-term treatment of cerebral aspergillosis with high-dose voriconazole guided by therapeutic drug monitoring.

We report the case of a patient who had cerebral aspergillosis after otorhinolaryngologic surgery and who was successfully and safely treated with high-dose voriconazole (200 mg q6h) for more than 1 year thanks to a TDM-guided approach coupled with pharmacological review and with genotyping of CYP2C19 polymorphisms. The findings support the idea that personalized medicine based on TDM coupled with the need of avoiding drug-drug interactions may be helpful for maximizing the net benefit (probability of efficacy vs. probability of adverse events) of voriconazole in the management of long-term treatment of cerebral aspergillosis.

Cerebral aspergillosis in a patient on ibrutinib therapy-A predisposition not to overlook.

Ibrutinib has revolutionized the treatment of B-cell malignancies since its approval for chronic lymphocytic leukemia. It is also used in mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenstrom's macroglobulinemia, among others. It is a Bruton's tyrosine kinase inhibitor that acts on B-cell receptor signaling pathway and predisposes to various infections due to its effects on neutrophils, monocytes and T cells. We present a case of cerebral invasive aspergillosis in a patient being treated with ibrutinib for relapsed chronic lymphocytic leukemia. It was hard to associate the condition to ibrutinib versus the chronic lymphocytic leukemia. The patient was successfully treated with a combination of voriconazole and micafungin, resulting in complete recovery and no residual deficits. This highlights the importance of recognizing the rare complication in those on ibrutinib and initiating the treatment immediately with appropriate antifungal agents to improve prognosis of this potentially fatal condition.

Fatal case of cerebral aspergilloma complicated by ventriculitis and bacteremia due to Salmonella species in a sickle cell disease patient.

To describe a fatal case of invasive Aspergillus flavus sinusitis in a 43-year old female with sickle cell disease (SCD) complicated by intracerebral aspergilloma and invasive Salmonella infection. Cerebral aspergilloma carries a very high mortality rate. The patient developed post-craniotomy intracerebral hemorrhage at the site of biopsy, Salmonella species sepsis and ventriculitis. She presented with a 2-month history of headache, dizziness, personality and behavioral changes, and vomiting. Initial clinical evaluation raised the suspicion of brain tumor. Brain magnetic resonance imaging revealed a left frontal, thick-walled ring-enhancing lesion with extensive surrounding edema suggestive of a neoplastic lesion, or a contiguous inflammatory or infectious process from the skull base. Despite early diagnosis and appropriate antifungal and surgical management, she eventually died from severe infection and respiratory arrest. In conclusion, invasive aspergillosis should be included in the differential diagnosis of SCD patients with central nervous system (CNS) lesions.

Intracranial Fungal Infection After Solid-Organ Transplant.

Neurologic complications after solid-organ transplant reveal a great spectrum of pathologies. Intracranial hemorrhages, cerebral ischemic lesions, infarctions, lymphoproliferative disorders, and infections, including aspergillosis, have been observed after liver transplant. Fungi constitute nearly 5% of all central nervous system infections, mainly occurring in immunocompromised patients. The most common causative agent is Aspergillus species. It presents either as maxillary sinusitis or pulmonary infection. Brain involvement of Aspergillus carries a high rate of mortality. Aspergillosis presents in the forms of meningitis, mycotic aneurysms, infarctions, and mass lesions. Aspergillosis does not have a specific radiologic appearance. Parenchymal aspergillosis has heterogenous signal intensity (hypointense on T1-weighted and hyperintense on T2-weighted images). Here, we present 3 patients who underwent solid-organ transplant and developed central nervous system aspergillosis. Different modalities of neurosurgical intervention were performed in combination with chemotherapy as part of their fungal therapy.

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

BACKGROUND AND PURPOSE: CNS 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. METHODS: Retrospective 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. RESULTS: The 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. CONCLUSION: CNS 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.

Intracranial Aspergillosis in an Immunocompetent Young Woman.

Intracranial aspergillosis (ICA) is very rare in the immunocompetent individuals, usually misdiagnosed as a tumor or an abscess. A high index of clinical suspicion is required in patients who present with focal neurological deficits, headache, or seizures. We report the case of a 25-year-old immunocompetent female, who presented with a 15-month history of headache, seizures, left-sided proptosis and ophthalmoplegia, and right hemiparesis. Recovery from the symptoms and decrease in the lesion size seen on the radiological assessment were achieved through two decompressive craniotomies followed by prolonged combined systemic antifungal therapies. Although the initial neuroimaging suggested a mitotic pathology, the surgical sample confirmed ICA. Now the patient is on single antifungal therapy (Tab. voriconazole, 200 mg twice daily) and doing her daily activities, but with a reduced intelligent quotient. We report a challenging case of ICA where multiple courses of combined antifungal therapies and repeat surgeries paved the way for a good prognosis.

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.

Surgical Treatment Alone of Cerebral Aspergillosis in Immunocompetent Patient.

Aspergillosis is a disease that predominantly affects immunocompromised patients. The incidence in immunocompetents is rare, and manifestation is generally pulmonary. Few reports in the literature refer to isolated cerebral aspergillosis in individuals with no chronic comorbidities. We describe a case of a 59-year-old rural worker without previous pathologies who had a partial convulsive crisis in a subtle form, with self-limiting and nonrecurrent secondary generalization. Diagnostic investigation demonstrated a subcortical tumorlike lesion in the right precentral gyrus by nuclear magnetic resonance that allowed en bloc microsurgical resection, with histopathologic findings indicating cerebral aspergillosis. Because of the delay in obtaining the result of the biopsy due to technical difficulties with analysis, the diagnosis was delayed. The patient was clinically stable, with imaging without modifications and with negative serologic tests, so it was decided to follow the patient without antifungal therapy, which was successful. This was a case of isolated cerebral aspergillosis in an immunocompetent individual who was successfully treated by complete resection of the lesion alone, without combined antifungal therapy.

[Cerebral aspergillosis in an immunocompromised patient with follicular lymphoma].

We present a case of central nervous system aspergillosis in an immunocompromised 69-year-old male with a history of chemotherapeutic treatment for follicular lymphoma. The patient presented with aphasia, apraxia and confusion. An MRI of the central nervous system and Aspergillus antigen in the spinal fluid was suggestive for this invasive fungal infection. Despite treatment with voriconazole the patient succumbed to the infection. A rise in rare, severe infectious complications as presented is expected due to increasing dose-intensity of chemotherapy.

Brain targets: can you believe your own eyes?

The unquestionable advantages provided by modern neuroimaging techniques have recently led some to question the duty of the neurologist, traditionally struggling first and foremost to establish the semeiotic localization of brain lesions and only then to interpret them. The present brief report of six clinical patients who came recently to our attention aims to emphasize that the interpretation of neuroimaging results always requires integration with anamnestic, clinical and laboratory data, together with knowledge of nosography and the literature. The solutions of the reported cases always originated from close interaction between the neurologist and the neuroradiologist, based on the initial diagnostic uncertainty linked to the finding of isolated or multiple brain target or ring lesions, too often considered paradigmatic examples of the pathognomonic role of neuroimaging.

Aspergillosis after liver transplantation in the context of common variable immunodeficiency: case report.

Common variable immunodeficiency (CVID) is the most common primary immune defect, resulting in hypogammaglobulinemia as well as deficits in cell-mediated immunity. Although it mainly manifests in immunodeficiency and related infection, CVID can also be associated with autoimmune phenomena such as immune thrombocytopenic purpura, hemolytic anemia, rheumatoid arthritis, lupus, primary biliary cirrhosis, and autoimmune hepatitis (AIH). AIH is a less common but serious complication of CVID, which can result in early cirrhosis, ascites, and even hepatocellular carcinoma. Here, we discuss a recent case of transplantation for cirrhosis secondary to AIH in the context of CVID. Although the patient's surgery occurred without complication, he rapidly developed fulminant alveolar hemorrhage and seizures, and died secondary to disseminated neuroaspergillosis.

[Intracranial propagation of invasive aspergilloma in an immuncompromised patient]. / Intracranialis terjedést mutató invazív aspergilloma immunszupprimált beteg esetében.

Aspergillus infection of the central nervous system is a rare disease, occasionally seen among immunocompromised patients. The most frequent pathway is hematogenic dissemination. Less known is the direct propagation from the paranasal sinuses, which is usually observed in immunocompetent patients. We report a patient who developed cavernous sinus syndrome due to an invasive intracranial aspergilloma after longlasting chemo- and steroid therapy for chronic lymphoid leukemia and immunhemolytic anemia. The characteristic features seen on radiological images--brain CT and MRI--suggested the possibility of invasive aspergilloma. Postoperative histology defined the diagnosis. Our case review highlights the importance of considering the possibility of an invasive opportunistic infection of the CNS in an immunocompromised patient presenting a new neurological sign.

Imaging findings in intracranial aspergillus infection in immunocompetent patients.

AIM: To study the neuroimaging features of craniocerebral aspergillosis infection in immunocompetent patients. MATERIALS AND METHODS: The clinical and imaging data of 12 patients of aspergillus fungal infection were retrospectively reviewed. Diagnosis of fungal infection was confirmed by histopathologic examination of surgically excised specimen, stereotactic biopsy material, or endoscopic sinus biopsy. The radiologic studies were evaluated for anatomic distribution of lesions, signal intensity, contrast enhancement, presence of hemorrhage, diffusion restriction, perfusion, and spectroscopy characteristics. Medical records, biopsy reports, and autopsy findings were also reviewed. RESULTS: Twelve cases of aspergillosis infections in immunocompetent patients were diagnosed at our hospital over a period of 10 years. Lesions could be classified based on imaging of lesions of sinonasal origin, intracranial mass lesion including both parenchymal or extraparenchymal meningeal based and stroke. Coexisting meningitis was also noted in one patient. Disease of sinonasal origin commonly showed invasion of the cavernous sinus and orbital apex resulting in visual symptoms and multiple cranial nerve palsies. Intracranial mass lesions without sinonasal involvement were seen in five cases that included isolated parenchymal lesion in two patients and dural-based mass lesions in three patients. Isolated intraparenchymal lesions included two cases of fungal cerebritis. Dural-based lesions were large granulomas with a significant mass effect. Infarcts were seen in three patients and angiography showed vessel narrowing or occlusion in all the three patients. CT demonstrated isodense to hyperdense attenuation of primary sinus disease with evidence of bone destruction in all the cases of sinonasal origin. Primary parenchymal lesions showed heterogenous attenuation with predominantly low-density areas. Dural-based lesions showed isodense to hyperdense attenuation. Magnetic resonance imaging revealed isointense to hypointense signal intensity on both T(1)-weighted (T1W) and T(2)-weighted (T2W) images in all lesions of sinonasal origin and isolated dural-based mass lesions. Primary parenchymal lesions showed heterogenous signal intensity pattern with predominantly hypointense signal on T1W and hyperintense signal on T2W images. Diffusion weighted imaging, magnetic resonance spectroscopy, and perfusion-weighted imaging gave valuable ancillary information in these cases. CONCLUSION: Sinonasal disease with intracranial extension is the commonest pattern of aspergillus infection followed by intracranial mass lesions. Hyperdense sinonasal disease with bone destruction and intracranial extension on computed tomography, hypointense signal intensity of the lesions on T2W magnetic resonance images, presence of areas of restricted diffusion, decreased perfusion on perfusion-weighted imaging, and presence of hemorrhages are key to the imaging diagnosis of fungal infection.

Sphenoid sinus aspergillosis simulating pituitary tumor in immunocompetent patient.

Aspergillosis of the sphenoid sinus is rare in immunocompetent patients. It may be mistaken for a sellar region tumor. A 65-year-old, human immunodeficiency virus-negative man presented with a 3-week history of cranial nerve III paresis and visual deterioration. The patient had a long-term history of tobacco snuff abuse. CT scans and MRI demonstrated a space-occupying lesion of the sellar and sphenoid sinus region. Presumptive diagnosis of pituitary macroadenoma was made and the patient was operated on via a transnasal-transsphenoidal approach. After the sphenoid sinus was opened, a yellow-brownish gluey material with crumbly debris extruded and was aspirated. The dura was intact. Histopathology revealed numerous Aspergillus hyphae without tissue invasion. Postoperatively, the cranial nerve III paresis resolved in a few days and visual acuity improved. Sphenoid sinus aspergillosis should be included in the differential diagnosis of sellar region processes, even in immunocompetent patients. Early diagnosis and transsphenoidal removal provides good results without the need for systemic antifungal therapy in non-invasive aspergillosis.

Granulomatous infectious disease in an immunosuppressed patient: a case report with radiological and pathological correlation.

We report here on a case of disseminated aspergillosis in an immunocompromised patient with Wegener's granulomatosis to illustrate the complexity of brain imaging diagnosis in the presence of concomitant infectious, immunological and ischemic diseases.

Bilateral mycotic cerebral abscess due to aspergillosis--a case report.

Aspergillosis of central nervous system is an uncommon infection mainly occurring in immunocompromised patient. It may be present in several forms: abscess, meningitis, mycotic aneurysm, infarction and in tumoral form. Here we report a case of cerebral aspergillosis presenting as bilateral frontal lobe abscess without evidence of any underlying systemic disorder or extracranial disease.

Cerebral aspergillosis in the critically ill: two cases of successful medical treatment.

OBJECTIVE: Invasive aspergillosis is associated with a poor prognosis, especially in critically ill patients with cerebral involvement. We present two cases of cerebral invasive aspergillosis successfully treated in the intensive care unit with combination antifungal therapies and without surgery. CASE PRESENTATION: The first patient was a 49-year-old man with rheumatoid arthritis who received corticosteroid and cyclophosphamide treatment and developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole the patient had a successful outcome with voriconazole and liposomal amphotericin B therapy. The patient returned home after an 8-month hospital stay. The second patient was a 54-year-old woman with pulmonary neoplasia and corticosteroid treatment who developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole and liposomal amphotericin B therapy the patient had a favorable outcome with liposomal amphotericin B and caspofungin therapy. The patient died 10 months after initial diagnosis of cardiac tamponade unrelated to fungal infection. DISCUSSIONS: These cases illustrate the improving prognosis of invasive aspergillosis due to the availability of new treatments, especially in cases of cerebral involvement. It also demonstrates that the outcome of critically ill patients requiring mechanical ventilation for invasive aspergillosis can be favorable. The treatment of patients with invasive cerebral aspergillosis in the intensive care setting should be encouraged.