Angioinvasive Aspergillus-associated Stroke in an Immunocompetent Host Following Cardiac Surgery and ECMO.

INTRODUCTION: Invasive cerebral aspergillosis is an uncommon cause of stroke among immunocompetent patients and has not been reported in association with cardiac surgery or extracorporeal membrane oxygenation (ECMO). We report the case of an immunocompetent host who developed aspergillus-associated stroke following coronary artery bypass graft (CABG) and ECMO. CASE REPORT: A 59-year-old woman developed cardiogenic shock after 3-vessel-CABG requiring intra-aortic balloon pump placement and subsequent veno-arterial ECMO. Noncontrast computed tomography of the brain was suggestive of multiple bihemispheric ischemic infarcts. Postmortem pathologic analysis revealed aspergillus-associated inflammation of blood vessels and ischemic and petechial hemorrhagic strokes in the affected territories. DISCUSSION AND CONCLUSIONS: Ischemic infarcts in the setting of CABG or ECMO are often presumed to be thromboembolic from the heart or device, related to underlying hemodynamic instability, or due to a clinically apparent systemic infection such as endocarditis. This report suggests that invasive cerebral aspergillosis should be considered in seemingly immunocompetent patients following CABG or ECMO. The mechanism is unclear, but may be related to systemic inflammatory dysregulation resulting in increased susceptibility to uncommon pathogens.

Malignant fungal infection of the cavernous sinus: case report.

Intracranial spread of fungal infection is a life-threatening condition that usually affects immunocompromised patients. Here the authors present a case of biopsy-proven Aspergillus fumigatus infection of the paranasal sinuses in an immunocompetent patient with documented spread to the orbit, cavernous sinus, and petrous apex despite medical antifungal treatment. As a life-saving treatment, cavernous sinus resection with external carotid artery-middle cerebral artery bypass was performed. The authors discuss the literature regarding the intracranial spread of paranasal sinus fungal infections in immunocompetent patients and management strategies.

[Cerebral aspergillosis and liver transplantation: about one case]. / Aspergillose cérébrale et transplantation hépatique: discussion autour d'un cas.

Cerebral invasive aspergillosis is a rare but serious infection. Mortality is still high despite appropriate treatment. We report the case of a patient with liver transplantation in the context of alcoholic cirrhosis and transplanted back seven years later consequently to an ischemic cholangitis. Following an acquired active viral infection by HCV and treated by antiviral combination therapy the patient presented six months after this second operation a cerebral aspergillosis of tumour-like presentation. It rapidly evolved to an unfavourable outcome with intracranial hypertension state. If the therapeutic management is well established, the diagnosis is difficult. This observation allows us to discuss the various diagnostic criteria of cerebral aspergillosis.

Aspergilosis nasosinusal con extensión intracraneal en una paciente inmunocompetente: una entidad infrecuente con características radiológicas típicas / Sinonasal aspergillosis with intracranial extension in an immunocompetent patient: a rare disease with typical imaging features

El aspergilo es un hongo ubicuo. Las localizaciones de infección primaria más comunes son el tracto respiratorio y los senos paranasales. La afectación intracraneal es rara y conlleva una alta mortalidad. Ocurre mayoritariamente por extensión hematógena desde el pulmón, pero en pacientes inmunocompetentes, la extensión directa desde los senos paranasales es más común. Describimos el caso de una mujer de 25 años originaria de India que se presentó en el servicio de urgencia de nuestro centro hospitalario con cefalea frontal crónica y progresiva. Los hallazgos en los estudios de imágenes sugirieron el diagnóstico de sinusitis fúngica con extensión intracraneal, siendo el patógeno más frecuente el aspergilo. El diagnóstico fue confirmado anátomo-patológicamente. Revisamos los hallazgos radiológicos típicos que deben ayudar al diagnóstico precoz de esta entidad, rara, pero potencialmente mortal.

Aspergillus is a ubiquitous fungus. The most common primary sites of infection are the respiratory tract and sinuses. Intracranial infection is rare and implies a high mortality. It occurs mainly by hematogenous extension from the lung, but in immunocompetent patients, direct extension from the sinuses is more common. We describe the case of a 25 year old woman from India who consulted in the emergency room of our hospital with chronic and progressive frontal headache. The findings in imaging studies suggested the diagnosis of fungal sinusitis with intracranial extension, being the most common pathogen of Aspergillus. The diagnosis was anatomically-pathologically confirmed. We review the typical radiological findings which should help in the early diagnosis of this rare but potentially fatal disease.

Central nervous system aspergillosis: a series of 14 cases from a general hospital and review of 123 cases from the literature.

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.

47 year-old man with HIV infection and hemiplegia.

CNS aspergillosis is often missed in the setting of advanced HIV infection, especially in the absence of presumed risk factors such as neutropenia or prior steroid treatment. We describe the postmortem evaluation of the brain of a patient with AIDS that developed progressive neurologic deterioration. Sequence brain MRIs, CSF analysis, and multiple presumed treatments failed to reveal the possible causes or improve his ongoing condition. His brain autopsy showed numerous abscesses with septated hyphae consistent with CNS angioinvasive aspergillosis.

Aspergillus-associated cerebral aneurysm successfully treated by endovascular and surgical intervention with voriconazole in lupus nephritis patient.

During the last five decades, long-term therapy with immunosuppressive agents such as pulse cyclophosphamide in conjunction with high-dose corticosteroids has enhanced both patient survival and renal survival in patients with diffuse proliferative lupus nephritis. Nevertheless, severe side effects such as infectious complications remain the main cause of morbidity and mortality. Central nervous system aspergillosis is uncommon but life-threatening in lupus patients. In this single-patient case study, carotid aneurysm with sphenoidal sinusitis was suspected when severe epistaxis occurred during cyclophosphamide pulse therapy. With anti-fungal therapy, a graft stent was successfully deployed to the aneurysm and specimens of sphenoidal mucosa showed typical hyphae, indicating aspergillosis. Three months after stopping voriconazole treatment, two cerebral aneurysms that were revealed on MR images were successfully removed by aneurysmal clipping. The patient remained alive at one-year follow-up with lupus nephritis in remission. The rarity and high mortality of aspergillus-related fungal aneurysms have led to most cases being recognized postmortem. However, such aneurysms must be diagnosed early to prevent fatal complications by performing appropriate management such as surgical procedure or endovascular intervention.

Twenty-nine cases of invasive aspergillosis in neutropenic patients.

INTRODUCTION: Invasive aspergillosis is a life-threatening infectious complication in hematological patients undergoing immunosuppressive chemotherapy. PATIENTS AND METHODS: We report 29 cases of invasive aspergillosis diagnosed in the Sousse Farhat Hached hospital Hematology unit, Tunisia, between 2002 and 2010. RESULTS: The most frequent disease (65.5%) was acute myeloid leukemia. All patients were severely neutropenic (<500/mm(3), mean duration=27 days). Pulmonary invasive aspergillosis was suggested in 28 (96.5%) cases. The most frequent respiratory signs were cough (64.3%), chest pain (53.6%), and hemoptysis (50%). The chest X-ray showed suggestive lesions in 60.7% of cases. CT scans revealed nodules with cavitation in 65% of cases, a halo sign in 20% of cases, and nodules in 15% of cases. Galactomannan antigenemia was positive in 88%, mycological examination positive in 51.6%, and seroconversion was noted in 35.7% of the cases. Invasive pulmonary aspergillosis was classified, according to EORTC/MSG criteria, as probable in 26 cases, possible in one case, and proven in one case. Aspergillus flavus was the dominant species in pulmonary invasive aspergillosis accounting for 73.7% of isolates. Extrapulmonary involvement was suggested in 39.3% of cases, the most frequent were sinusitis and brain abscess. Primary cutaneous aspergillosis was observed in one case. The overall mortality rate was 64.2%; the 12-week survival rate was 71.4%. CONCLUSION: Our results are correlated to published data. A. flavus was the most frequent species in our region.

Importancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del SNC / Importance of images and etiological diagnosis of central nervous system envolvement in immunocompromised patient

We report a 16 years old boy with diagnosis of Acute Myeloid Leukemia with severe immune suppression secondary to his primary disease and to leukemia's treatment. Early during the course of his chemotherapy he developed symptoms and signs compatible with invasive fungal disease (IFD). Lungs were primarily compromised followed by CNS involvement with manifestations of intracranial hypertension. Laboratory exams were remarkable for prolonged neutropenia and indirect evidence of Aspergillus sp infection, with successive detection of positive and increasing levels of galactoman antigen in serum. With this case we want emphasize the great importance of invasive fungal disease in immune suppressed patients and particularly the CNS compromise. This represents a medical emergency which deserves to start a complete and comprehensive microbiology diagnosis and concomitantly start an empiric antifungal treatment. The importance of neuroimaging for a correct identification of the number, location and size of CNS lesions must be highlighted. The election of MRI, if available, should be preferred due to a better performance than CT scan. Brain biopsy should be discussed when all the non invasive attempts for etiology identification have failed. The invasive fungal CNS compromise has medical treatment and the surgical drainage has to be considered for lesions greater than 2 cm or for those making a mass effect or have failed with medical treatment.

Comunicamos el caso de un adolescente de 16 años, con una leucemia mieloide aguda y una grave inmunosupresión secundaria a su enfermedad y el tratamiento. Precozmente post-quimioterapia desarrolló síntomas y signos compatibles con una enfermedad fúngica invasora (EFI). Inicialmente se afectaron sus pulmones y a continuación el SNC con hipertensión intracraneal. Los exámenes de laboratorio indicaron una neutropenia prolongada y evidencias indirectas de una infección por Aspergillus sp mediante la medición sucesiva de galactomanano positivo en sangre y un segundo valor en ascenso. Con este caso enfatizamos la gran importancia que tienen las EFI en pacientes inmunocomprometidos, particularmente sobre el SNC. Ellas representan una emergencia médica que requiere de una confín-nación microbiológica y el inicio temprano de terapia anti-fúngica empírica. Debe destacarse la importancia que tienen las neuro-imágenes en la correcta identificación del número de lesiones, su localization y tamaño. La RM, si está disponible, debiera ser la elección, para una mejor definición, por sobre el uso de la TAC. Igualmente, debiera discutirse la indicación de biopsia cerebral cuando todos los métodos no invasores han fracasado en precisar la etiología. La EFI del SNC es de tratamiento médico, debiéndose considerar el drenaje quirúrgico de las lesiones con más de 2 cm de diámetro o aquellas que ejercen efecto de masa o, finalmente, cuando ha fracasado el manejo con anti-fúngicos.

[Importance of images and etiological diagnosis of central nervous system involvement in immunocompromised patient]. / Importancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del SNC.

We report a 16 years old boy with diagnosis of Acute Myeloid Leukemia with severe immune suppression secondary to his primary disease and to leukemia's treatment. Early during the course of his chemotherapy he developed symptoms and signs compatible with invasive fungal disease (IFD). Lungs were primarily compromised followed by CNS involvement with manifestations of intracranial hypertension. Laboratory exams were remarkable for prolonged neutropenia and indirect evidence of Aspergillus sp infection, with successive detection of positive and increasing levels of galactoman antigen in serum. With this case we want emphasize the great importance of invasive fungal disease in immune suppressed patients and particularly the CNS compromise. This represents a medical emergency which deserves to start a complete and comprehensive microbiology diagnosis and concomitantly start an empiric antifungal treatment. The importance of neuroimaging for a correct identification of the number, location and size of CNS lesions must be highlighted. The election of MRI, if available, should be preferred due to a better performance than CT scan. Brain biopsy should be discussed when all the non invasive attempts for etiology identification have failed. The invasive fungal CNS compromise has medical treatment and the surgical drainage has to be considered for lesions greater than 2 cm or for those making a mass effect or have failed with medical treatment.

[Skull-base plasmacytoma with craniocervical instability]. / Plasmocitoma de base craneal con inestabilidad cráneo-cervical.

INTRODUCTION: Cranio-cervical instability is, in some cases, the main surgical concern in posterior skull base tumors. We report on a case in which a solitary plasmacytoma of the skull base presented with cranio-cervical instability. Vertebral artery was injured during surgery. The surgical anatomy is reviewed, with emphasis in vascular complications avoidance. CASE REPORT: A 66 year-old woman was diagnosed of a cranial base solitary plasmacytoma and treated with radio and chemotherapy with complete remission. After receiving that treatment, she presented with tetraparesis and a cranio-cervical instability was diagnosed. She was operated on, under cranial traction, of posterior occipito-cervical instrumentation with C1 to C2 transarticular Magerl screws. The right vertebral artery was injured during surgery without additional neurological deficit. Two years after the operation she remains independent for daily activities. CONCLUSIONS: Transarticular screws at the C1 to C2 level of the cervical spine may provide rigid fixation in posterior cranio-cervical instrumentation for osteolytic lesions, but there is a risk of injury to the vertebral artery, specially when some variations in the surgical anatomy exist.

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.

[Invasive aspergillosis in an immunocompromised patient: clinical and therapeutic considerations]. / Aspergillosi invasiva in paziente immunocompromesso: considerazioni cliniche e terapeutiche.

The paper describes a case report of a young female with invasive aspergillosis diagnosed after brief treatment with high-dose steroids for autoimmune thrombocytopenia. Early diagnosis of invasive aspergillosis was made with cultures of tracheoaspirates and bronchoalveolar lavage and was confirmed with a transbronchial biopsy. After initial ineffective treatment with liposomal amphotericin B and dissemination from pulmonary to central nervous system involvement, treatment was switched to a combination of voriconazole and caspofungin. After marked clinical and radiological improvement, treatment was switched to the orally administered formulation of voriconazole until the complete disappearance of central nervous system lesion was observed. In the discussion section we underscore the most significant data of the host susceptibility, diagnosis of invasive aspergillosis, complications and treatment. This case ably demonstrates the efficacy of new antifungal agents, even when administered orally, and underscores the variability of host susceptibility to atypical and often unexpected invasive fungal infections.

[Intracranial aspergillosis in an immunocompetent patient]. / Immün kompetan bir hastada intrakranial aspergilloz.

Intracranial aspergillosis is a rare clinical picture, but the mortality rate is very high. In this report, an immunocompetent 43 years old male patient with mortal intracranial aspergillosis was presented. The patient has been admitted to Neurosurgery Clinics of our hospital with the complaints of weakness and walking difficulties. In the cranial tomography a brain mass was detected, and his medical history revealed that he had experienced an operation 18 months ago because of another intracranial tumour. After the operation his fever was high (39 degrees C), the leukocyte count, erythrocyte sedimentation rate and CRP values were increased, and purulent discharge was present in the operation site. As the pathological examination of the operation material have suggested aspergillosis, conventional amphotericin B treatment was started initially, but has changed to liposomal form 18 days later. Aspergillus fumigatus has been grown on the exudate culture collected from flap region. The levels of immunoglobulins and complement components of the patient were found normal. Since his next cranial magnetic resonance result indicated the presence of pansinusitis and destructive lesions in ethmoid sinuses, caspofungin was added to the therapy. The patient has reoperated since there was no clinical and laboratory progress at the 83rd day of amphotericin B, and 10th day of caspofungin therapy. Bacterial and fungal cultures of specimens collected during the second operation yielded negative results, however microabscesses and chronic inflammation focci were detected in histopathological examination. Fever and purulent discharge recurred in the patient after the second operation and visual defect has developed in his left eye. There was no bacterial or fungal growth in the discharge material, but direct microscopy have showed the presence of septate hyphae. The patient was discharged from the hospital by his family request with oral itraconazole treatment, however, he died one month later. Since no immunosuppressive status was detected in our patient, the transmission was thought to occur during the operation which he had experienced one and half year ago. In conclusion, the patients who experience neurosurgery should be followed-up carefully in terms of aspergillosis.