Clinical History
A 58-year-old male patient with a history of orthotopic heart transplantation was admitted to the hospital due to progressive decrease in awareness. Cerebral MRI showed lesions compatible with abscesses and Aspergillus fumigatus was isolated in bronchoalveolar lavage. Despite aggressive antifungal therapy with variconazole and interferon-gamma, the patient died a month later.
Imaging Findings
MR images show multiple lesions with intense diffusion restriction, small (up to 1 cm diameter) with little or no mass effect. They present hypointense rings on T2-weighted image and contrast ring enhancement on T1-weighted image. (Fig. 1) The hypointense peripheral rim was better depicted on susceptibility-weighted imaging (Fig. 2) These findings suggested abscesses from haematogenous dissemination.
Thoracic CT shows large left pleural effusion with passive atelectasis of the entire left lower lobe and consolidation in lingula with heterogeneous enhancement of the lung parenchyma suggesting ischaemia / abscessification. Internal cavitation was not identified. (Fig. 3)
Cerebral MRI findings and positive bronchoalveolar lavage for Aspergillus fumigatus led to the diagnosis.
A follow-up brain MRI 12 days later showed a large intraparenchymal haemorrhage in the subinsular region with intraventricular extension. (Fig. 4)
Discussion
Aspergillus is a commonly encountered mold that is ubiquitous throughout the world. It can be found in soil, water, and decaying vegetation. [1] Although more than 350 individual species of this fungus exist, Aspergillus fumigatus is the most common pathogen involved in invasive tissue disease. [2]
Like most of fungal CNS infections, cerebral aspergillosis happens with an underlying predisposition such as acquired immunodeficiency syndrome, neutropenia, haematological malignancies, chemotherapy, malnutrition, prolonged corticosteroid therapy, and chronic systemic diseases such as diabetes and chronic renal failure. [3, 4]
In majority of cases, the primary site of infection is the lungs from where the Aspergillus hyphae disseminates via haematogenous spread to the CNS. Less frequent is the contiguous spread from paranasal sinuses where it manifest as an invasive fungal rhinosinusitis.
The angioinvasive character of the fungus characterises the clinical presentation of CNS aspergillosis. The hyphae tend to invade blood vessels resulting in vascular thrombosis and haemorrhagic infarcts. These sterile infarcts turn into septic infarcts, when the fungus erodes through the vessel wall and extends into the surrounding tissue, causing a mixed inflammatory reaction and necrosis. Typical findings include therefore multiple infarcts, intracranial haemorrhage, mycotic aneurysms and also granulomas and encephalitis, with or without abscess formation. [1, 2, 5] Meningitis and meningoencephalitis can also occur. [2, 4]
MRI will show multiple lesions with diffusion restriction and a random distribution in the brain parenchyma. They may be surrounded by a peripheral hypointensity on T2-weighted images, which is likely attributed to haemorrhage, haemosiderin-laden macrophages and a dense population of hyphae around the abscess. [2] This hypointense rim is better depicted on T2*-weighted images and susceptibility-weighted images. Lesions can show ring enhancement that may be subtle or well-defined, depending on the patient’s immune status. The presence of true ring or nodular enhancement, consistent with abscess or granuloma formation, indicates that the host defense system is able to isolate or encapsulate the organisms. [1, 5]
A differential diagnosis for such presentation includes ischaemic infarcts from cardiogenic emboli, multiple infarcts resulting from septic bacterial emboli, and metastatic tumours. [6]
Cerebral aspergillosis is a life-threatening condition and survival depends on early diagnosis and administration of intravenous antifungal therapy. Multiple cerebral infarctions in a patient considered at risk for invasive aspergillosis even without overt pulmonary disease is an indication to institute aggressive antifungal therapy. [5, 7]
Differential Diagnosis List
Angioinvasive cerebral aspergillosis
Ischaemic infarcts from cardiogenic emboli
Septic bacterial emboli
Metastatic tumours
Final Diagnosis
Angioinvasive cerebral aspergillosis
